Clinical trial NCT02848001
Conditions: Leukemia, Myeloid, Acute Myelodysplastic Syndromes
Keywords: CC-90009 Hematologic Cancers Leukemia Acute Myeloid Leukemia Myelodysplastic Syndrome AML MDS
Sponsor: Celgene
Start date: 2016-11-14; Completion date: 2024-04-11
Enrollment: 101 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
CC-90009-AML-001 is a phase 1, open-label, dose escalation and expansion, study in subjects with relapsed or refractory acute myeloid leukemia and relapsed or refractory higher-risk myelodysplastic syndrome.

Detailed description:
Study CC-90009-AML-001 is an open-label, Phase 1, dose escalation and expansion, first-in-human clinical study of CC-90009 in subjects with relapsed or refractory acute myeloid leukemia (AML) and relapsed or refractory higher-risk myelodysplastic syndrome.

The dose escalation part (Part A) of the study will evaluate the safety and tolerability of escalating doses of CC-90009 in relapsed and refractory AML. The expansion part, (Part B), will further evaluate the safety and efficacy of CC-90009 administered at or below the maximum tolerated dose (MTD) in selected expansion cohorts of one or more dosing regimens in order to determine the recommended Phase 2 dose (RP2D) for subjects with relapsed or refractory AML and relapsed or refractory higher-risk myelodysplastic syndrome.

Arms: arm 1: Will be administered intravenously per dosing schedule in a 28-day cycle. arm 2: Relapsed or refractory AML and MDS subjects. IP will be administered intravenously per dosing schedule determined in Part A
Interventions: intervention 1: CC-90009
Intervention descriptions: intervention 1: CC-90009

Protocol documents:
Prot_SAP_000.pdf: 
Official Title of Study: 
A Phase 1, Open-label, Dose Finding Study of CC-90009, a Novel Cereblon E3 Ligase Modulating 
Drug, in Subjects With Relapsed or Refractory Acute Myeloid Leukemia or Relapsed or Refractory 
Higher-Risk Myelodysplastic Syndromes 
NCT Number: NCT02848001 
Document Date (Date in which document was last revised): 31 Mar 2022 


CC-90009
Protocol CC-90009-AML-001
Celgene Corporation
CC-90009-AML-001 Amendment 9
Final: 31 Mar 2022
1
A PHASE 1, OPEN-LABEL, DOSE-FINDING STUDY OF CC-90009, A NOVEL 
CEREBLON E3 LIGASE MODULATING DRUG, IN SUBJECTS WITH RELAPSED OR 
REFRACTORY ACUTE MYELOID LEUKEMIA OR RELAPSED OR REFRACTORY 
HIGHER-RISK MYELODYSPLASTIC SYNDROMES
PROTOCOL NUMBER:
CC-90009-AML-001
DATE FINAL:
10 Mar 2016
AMENDMENT 1 FINAL:
27 Apr 2016
AMENDMENT 2 FINAL:
25 May 2016
AMENDMENT 3 FINAL:
22 Mar 2017
AMENDMENT 3.1 UK FINAL:
06 Dec 2017
AMENDMENT 4 FINAL:
16 Apr 2018
AMENDMENT 5 FINAL:
29 Nov 2018
AMENDMENT 6 FINAL:
16 Sep 2019
AMENDMENT 7 FINAL:
14 Jul 2020
AMENDMENT 8 FINAL:
10 Jun 2021
AMENDMENT 9 FINAL:
31 Mar 2022
EudraCT NUMBER:
2017-001535-39
IND NUMBER:
129252
SPONSOR NAME/ ADDRESS:
Celgene Corporation
86 Morris Avenue
Summit, NJ 07901
CONFIDENTIAL
This protocol is provided to you as an Investigator, potential Investigator, or 
consultant for review by you, your staff, and ethics committee/institutional review
board.  The information contained in this document is regarded as confidential 
and, except to the extent necessary to obtain informed consent, may not be 
disclosed to another party unless such disclosure is required by law or regulations.  
Persons to whom the information is disclosed must be informed that the 
information is confidential and may not be further disclosed by them.
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Protocol CC-90009-AML-001
Celgene Corporation
CC-90009-AML-001 Amendment 9
Final: 31 Mar 2022
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MEDICAL MONITOR / EMERGENCY CONTACT INFORMATION
Contact Information:
Name:
Title:
Address:
Phone:
E-mail:
Note: The back-up 24-hour global emergency contact call center should only be used if you 
are not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls.
Back-up 24-hour Global Emergency Contact Call Center: +1-877-501-7738
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Protocol CC-90009-AML-001
Celgene Corporation
CC-90009-AML-001 Amendment 9
Final: 31 Mar 2022
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CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE
{See appended electronic signature page}
Signature of Celgene Therapeutic Area Head
dd mmm yyyy
 
Printed Name of Celgene Therapeutic Area Head and Title
By my signature, I indicate I have reviewed this protocol and find its content to be 
acceptable.  
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Protocol CC-90009-AML-001
Celgene Corporation
CC-90009-AML-001 Amendment 9
Final: 31 Mar 2022
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Protocol CC-90009-AML-001
Celgene Corporation
CC-90009-AML-001 Amendment 9
Final: 31 Mar 2022
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SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Site Principal Investigator
dd mmm yyyy
Printed Name of Site Principal Investigator
Institution Name:_______________________________________
By my signature, I agree to personally supervise the conduct of this study at my study site 
and to ensure its conduct is in compliance with the protocol, informed consent, 
Institutional Review Board (IRB)/Ethics Committee (EC) procedures, instructions from
Celgene representatives, the Declaration of Helsinki, International Council for
Harmonisation (ICH) Good Clinical Practices Guidelines, and local regulations governing 
the conduct of clinical studies.
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Protocol CC-90009-AML-001
Celgene Corporation
CC-90009-AML-001 Amendment 9
Final: 31 Mar 2022
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COORDINATING PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Coordinating Principal Investigator
dd mmm yyyy
Printed Name of Coordinating Principal Investigator
Institution Name:_______________________________________
By my signature, I agree the protocol has been written to comply with ICH Good Clinical 
Practices guidelines and agree to offer guidance throughout the study as needed.
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Protocol CC-90009-AML-001
Celgene Corporation
CC-90009-AML-001 Amendment 9
Final: 31 Mar 2022
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OVERALL RATIONALE FOR PROTOCOL AMENDMENT 9:
The main purpose of this amendment is to provide mitigation strategies for the risk of serious 
and fatal infections with CC-90009 that was observed in the initial subjects in the Part B Dose 
Expansion.
Significant changes included in this amendment are summarized below:

Modification of CC-90009 dose and schedule for Part B Dose Expansion

Addition of dose modifications for concomitant use of strong CYP3A4 inhibitors in Part B 
Dose Expansion
The amendment also includes other minor clarifications and corrections: 

Update of prior clinical experience with CC-90009 to align with the most current version of 
CC-90009 Investigator’s Brochure, Edition 8.0 (Section 1.2.3 Prior Clinical Experience with
CC-90009).

Update of requirement of dexamethasone premedication for Days 1-7 schedule in Section 1.2.4 
Safety Monitoring Plan, Section 7.2 Treatment Administration and Schedule, and Section 8.3 
Required Concomitant Medications and Procedures.

Update of study duration based on current study status in Protocol Summary and Section 3.2 
Study Duration for Subjects.

Addition of safety follow-up of all adverse events/serious adverse events associated with 
confirmed or suspected severe acute respiratory syndrome coronavirus 2 infection in Section 
6.3.1 Safety Follow-up.

Exclusion of subjects from efficacy long term follow-up when new anti-cancer therapies are 
initiated in Section 6.3.2 Efficacy Long Term Follow-up 

Tables for Part A and Part B cohort at 3.6 mg Days 1-5 blood pharmacokinetic sampling 
schedules were moved from Section 6.5.1 to new Appendix Q.

The study will implement an updated CC-90009 Pregnancy Prevention Plan in Appendix L.
Additional revisions, including to sections of the Protocol Summary, have been made to align the 
protocol with respect to these changes. Other clarifications, corrections of minor typographical 
errors and incidental formatting changes were made throughout the document.
This protocol amendment applies to all subjects.
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 9
Section Number & Title
Description of Change
Brief Rationale
Section 1.2.3.1: Study 
CC-90009-AML-001
Section 1.3.4: Rationale 
for Dose and Dosing 

Added details of closure for 
initial Part B cohort at 
3.6 mg Days 1-5 and 
addition of the 2 new 
cohorts at 2.4 mg Days 1-7
A high rate of sepsis was 
observed in subjects enrolled in 
the initial Part B cohorts. 
Comprehensive analysis of 
available pharmacokinetics, 
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 9
Section Number & Title
Description of Change
Brief Rationale
Schedule in Part B Dose 
Expansion
Section 3.1: Study 
Design
Figure 4: High Level 
Study Design
Section 4.1: Number of 
Subjects
Section 7.2.8: Definition 
of Stopping Criteria 
Section 9.9.3: Stopping 
Rules Regarding 
Toxicity in Part B Dose 
Expansion 
Appendix P
and 3.0 mg Days 1-7
(updated in Section 1.2.3.1, 
Section 1.3.4, Section 3.1, 
Figure 4, and Section 4.1).

Added details of the non-
binding Bayesian method 
that will be utilized to 
monitor excess toxicities in 
Part B (updated in Section 
3.1, Figure 4, Section 7.2.8 
and included in new Section 
9.9.3 and new Appendix P).

Added details for Safety 
Review Committee (SRC) 
assessment of new doses 
and schedules for subjects 
enrolled in new cohorts in 
Part B (updated in Section 
3.1, Figure 4, Section 7.2.8 
and included in new Section 
9.9.3).
pharmacodynamics, efficacy, 
safety, and tolerability data 
were used to select the new 
doses and schedule for 
evaluation as part of a strategy 
to reduce the risk of sepsis. The 
SRC will continue to assess the 
tolerability of the doses and 
schedule used in Part B as 
described in the protocol and 
the expanded cohorts will be 
monitored for the excess 
toxicities, including sepsis, 
utilizing the non-binding 
Bayesian stopping criterion on a 
continuous basis.
Section 1.2.3.1: Study 
CC-90009-AML-001
Section 1.2.4: Safety 
Monitoring Plan
Section 1.3.4: Rationale 
for Dose and Dosing 
Schedule in Part B Dose 
Expansion
Section 7.2.15: Dosage 
Modifications for 
Concomitant Use of 
Strong CYP3A4 
Inhibitors in Part B Dose 
Expansion
Section 8.2: Prohibited 
Concomitant 
Medications and 
Procedures

Added exposure data for 
subjects who received 
strong CYP3A4 inhibitors
(Section 1.2.3.1 and Section 
1.3.4)

Added text for potential 
drug-drug interaction (DDI) 
with strong inhibitors of 
CYP34A (Section 1.2.4).

Section 7.2.1.5 added to 
include dose modifications 
in Part B for subjects on 
strong CYP3A4 inhibitors.

Added text for concomitant 
use of strong CYP3A4 
inhibitors and required dose 
reductions and for 
concomitant use of strong or 
moderate CYP3A4 inducers
(Section 8.2).
Analysis of CC-90009 plasma 
exposures in subjects who 
received strong CYP3A4 
inhibitors showed elevated 
exposures when compared to 
those who were not treated with 
strong CYP3A4 inhibitors, 
suggesting a potential DDI and 
possibility for increased 
toxicity. Dose reductions are
being used as part of the 
strategy to reduce the risk of 
sepsis for subjects receiving 
concomitant strong CYP3A4 
inhibitors.
Additionally, strong or 
moderate CYP3A4 inducers 
may decrease efficacy of 
CC-90009 and should be 
avoided.
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 9
Section Number & Title
Description of Change
Brief Rationale
Section 1.2.4 Safety 
Monitoring Plan
Added language regarding the 
Risk-Benefit Assessment.
With the integration of Celgene 
and BMS’ protocol 
development and risk-benefit 
assessment processes, the 
separate Celgene Risk-Benefit 
Assessment document has been 
retired. The information on 
relevant/potential risks and 
mitigation strategy has been 
transferred to the updated 
protocol during a protocol 
amendment. This change does 
not impact the Risk-Benefit of 
the study or compound.
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Celgene Corporation
CC-90009-AML-001 Amendment 9
Final: 31 Mar 2022
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PROTOCOL SUMMARY
Study Title
A Phase 1, Open-label, Dose-Finding Study of CC-90009, a Novel Cereblon E3 Ligase 
Modulating Drug, in Subjects with Relapsed or Refractory Acute Myeloid Leukemia or Relapsed 
or Refractory Higher-Risk Myelodysplastic Syndromes
Indication
Relapsed or refractory acute myeloid leukemia (R/R AML)
Relapsed or refractory higher-risk myelodysplastic syndromes (R/R HR-MDS) 
Objectives
Primary Objectives:

To determine the safety and tolerability of CC-90009. 

To define the non-tolerated dose (NTD), the maximum tolerated dose (MTD) and/or the 
recommended Phase 2 dose (RP2D) of CC-90009.  
Secondary Objectives:

To provide information on the preliminary efficacy of CC-90009 in R/R AML and R/R HR-
MDS.

To characterize the pharmacokinetics (PK) of CC-90009 in plasma and urine.
Exploratory objectives and pharmacodynamic (PD) endpoints for the study are outlined in Section 
2.
Study Design
Study CC-90009-AML-001 is an open-label, Phase 1, dose escalation and expansion, 
first-in-human clinical study of CC-90009 in subjects with relapsed or refractory AML (Appendix 
B) or in subjects with relapsed or refractory higher-risk MDS (Appendix E and G). The dose 
escalation part (Part A) of the study will evaluate the safety and tolerability of escalating doses of 
CC-90009, administered intravenously, and determine the MTD of CC-90009. In Part A, two 
formulations were tested. The expansion part (Part B) will further evaluate the safety and efficacy 
of CC-90009 administered at or below the MTD in selected expansion cohorts of up to 
approximately 20 evaluable subjects in each disease indication (R/R AML and R/R HR-MDS) in 
order to determine the RP2D. One or more dosing regimens may be selected for cohort expansion
(at a minimum, one in R/R AML and one in R/R HR-MDS). MDS subjects will only be enrolled 
during Part B. Parts A and B will consist of 3 periods:  Screening, Treatment, and Follow-up.
Leukemia response will be determined by the Investigator.  Disease assessment will be based on 
the International Working Group (IWG) Response Criteria in AML (Cheson, 2003; refer to
Appendix C). MDS response will be based on the IWG Response Criteria for Myelodysplasia 
(Cheson, 2006; refer to Appendix F).
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Screening Period
The Screening Period starts 28 days prior to first dose of CC-90009. The informed consent 
document must be signed and dated by the subject and the administering staff prior to the start of 
any other study procedures. All screening tests and procedures must be completed within the 
28 days prior to the first dose of CC-90009. For Part B of the study, subjects will be assigned to 
either the R/R AML or the R/R HR-MDS cohort based on a central laboratory diagnosis 
confirmation. 
Treatment Period
In the Treatment Period, CC-90009 will be administered intravenously on Days 1-5 of each 28 day 
cycle for up to 4 cycles in the absence of disease progression (as defined in Section 6.4), relapse, 
unacceptable toxicity, or subject/physician decision to withdraw. Modified dosing schedules (eg, 
increasing from 5 consecutive days to up to 7 or 10 consecutive days of dosing or increasing 
infusion length) may be evaluated in additional cohorts, if necessary, based on toxicity, PK 
profiles, and PD findings. An additional schedule of CC-90009 administered once daily on Days 
1-3 and Days 8-10 of each 28-day cycle will be explored. Those who demonstrate benefit from 
treatment without unacceptable toxicity (any complete remission [CR], morphologic leukemia-
free state [MLFS], partial remission [PR], or stable disease with discussion with Medical Monitor) 
may continue treatment beyond Cycle 4 until loss of that benefit, unacceptable toxicity, or 
subject/physician decision to withdraw.
All subjects will be required to start calcium, calcitriol, and vitamin D supplementation at least 
3 days prior to Day 1 of each cycle and continue until ≥ 3 days after the last dose of CC-90009 in 
each cycle (eg, ≥ Day 8 when CC-90009 is administered on Days 1-5, ≥ Day 10 when CC-90009 
is administered on Days 1-7, or ≥ Day 13 when CC-90009 is administered on Days 1-10 or Days 1-
3/Days 8-10).
In Cycle 1 of Part A, a bone marrow evaluation will be performed on Day 28 (± 3 days). Based on 
the Day 28 bone marrow evaluation, subjects with hypoplastic bone marrow, without evidence of 
persistent leukemia, who have Grade ≥ 3 neutropenia will be followed for an additional 2 weeks 
for safety monitoring in Cycle 1 (total duration of 42 days; refer to Figure 1). An additional bone 
marrow assessment will be performed at the time of hematologic recovery or Day 42 (± 3 days).  
Thus, in Part A, the window for evaluation of dose-limiting toxicity (DLT) during Cycle 1 will be 
up to 42 days (28 or 42 days). In Part B, Cycle 1 will be 28 days in length. Cycles ≥2 will be 28 
days in length. Subsequent cycles should start ≤ 7 days following the last day of the previous cycle.
Permitted treatment delays are described in Section 7.2.12. 
Follow-up Period
In the Follow-up Period, all subjects will be followed for 28 days (± 3 days) after the last dose of 
CC-90009 for safety. 
Subjects without documented progression of disease (or relapse) will have efficacy evaluations of 
complete blood counts and peripheral blood smears performed every subsequent 8 weeks 
(± 1 week) for the 1st year and every 12 weeks (± 2 weeks) for the 2nd year or until progression of 
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disease (or relapse), initiation of a new anticancer therapy, withdrawal of consent from the study, 
death, or the End of Trial, whichever comes first. A bone marrow evaluation will be completed at 
the end of the 1st year and as clinically indicated during the Follow-up Period.
All subjects will be followed for survival follow-up according to the schedule for the efficacy long-
term follow-up for up to 2 years or until death, lost to follow-up, or the End of Trial, whichever 
occurs first. Survival follow-up may be conducted by record review (including public records) 
and/or telephone contact with the subject, family, or the subject’s treating physician.
Part A-Dose Escalation
During the escalation phase (Part A), a modified accelerated titration design (Simon, 1997) will 
be used to establish initial toxicity.  Cohorts of one or more subjects each will be administered
CC-90009 at doses that will increase in 100% increments per cohort until ≥2 subjects experience 
a CC-90009-related Grade ≥2 adverse event in the DLT window (may be different cohorts), or 
≥1 subject experiences a DLT within the DLT window. At that time the current cohort and all 
subsequent cohorts will be expanded enrolling 3 to 6 subjects. A dose escalation schedule with 
dose increments not to exceed 50% will concurrently be initiated in order to establish the NTD 
and MTD (refer to Section 7.2.2). The initial dose will be 0.3 mg. Sample dose escalation schemes 
are shown in Figure 2. At the study start an initial formulation (Gen 1 CC-90009) will be utilized,
and during dose escalation a second formulation (Gen 2b CC-90009) will replace Gen 1
CC-90009. The N,N-Dimethylacetamide (DMA) residual solvent in the Gen 1 CC-90009 
formulation must not exceed the permitted daily exposure (PDE) limits set in the ICH Q3C 
Impurities: Residual Solvents in order to proceed with dose escalation cohorts above a daily CC-
90009 dose of 2.4 mg. The residual solvent (formic acid) level in the Gen 2b CC-90009
formulation allows daily doses of CC-90009 of up to 20 mg without exceeding its PDE set in the 
ICH Q3C guidance.
Dose escalation decisions will be made at the discretion of a Safety Review Committee (SRC) that 
will include Investigators (and/or designated representatives), the Sponsor’s study physician, 
safety physician, and the study manager. Ad hoc attendees may include the study 
pharmacokineticist, study statistician, and additional study clinical scientists. Other internal and 
external experts may be consulted by the SRC, as necessary. The Gen 2b CC-90009 formulation 
was introduced at the fourth dose level (DL4: 2.4 mg D1-5) (in accordance with study dose 
escalation guidelines) based on SRC recommendation after review of available study data from 
the initial three dose levels of Gen 1 CC-90009 formulation (0.3 mg D1-5, 0.6 mg D1-5 and 1.2 mg 
D1-5). 
The SRC may decide to evaluate a higher dose cohort, additional subjects within a dose cohort,
intermediate dose cohorts, smaller dose increments, alternate dosing schedules (eg, increasing 
from 5 to up to 7 or 10 consecutive days of CC-90009 administration or longer infusion times),
recommend or adjust dose or frequency of premedication requirements, and/or declare an MTD 
based on their review of available clinical and laboratory safety data, PK profiles, and PD findings. 
In the event that an alternate dosing schedule is evaluated, the starting dose and schedule will not 
exceed the dose intensity of a dose cohort that has previously met the criteria for dose escalation.
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An additional schedule of CC-90009 administered once daily on Days 1-3 and Days 8-10 of each 
28-day schedule may be explored (Figure 3). 
After the first dose is administered in any cohort during dose escalation, subjects in each cohort 
are observed for at least 28 days and up to 42 days (Cycle 1, DLT window) before the next higher,
dose cohort can begin. No more than one subject per day will be enrolled in a given dose escalation 
cohort. A subject evaluable for DLT is defined as one that: 

Has received at least 80% of the total planned Cycle 1 dose (eg, ≥ 4 CC-90009 doses for the 
Days 1-5 dose schedule to be completed on or before Day 10, ≥ 6 CC-90009 doses for the Days 
1-7 dose schedule to be completed on or before Day 10, ≥8 doses by Day 14 for the Days 1-10 
schedule, or ≥ 5 doses by Day 14 for the D1-3/D8-10 schedule) of CC-90009 during Cycle 1 
without experiencing a DLT,
Or

Experienced a DLT after receiving at least one dose (or fraction thereof) of CC-90009.  
In the event that an alternate dose schedule (eg, increasing from 5 days to up to 7 or 10 consecutive 
days of dosing) is evaluated in Part A, the same criteria for determining DLT-evaluable subjects 
will be applied. Subjects non-evaluable for DLT will be replaced.
A dose level (dose/schedule) will be considered intolerable if > 33% of evaluable subjects in a 
dose cohort experience DLT during Cycle 1. The MTD will be defined as the last dose below the 
NTD, at which ≤ 33% of evaluable subjects experienced DLT during Cycle 1. If 2 or more of 6 
evaluable subjects experience DLTs in the first dose cohort, a lower dose cohort may be explored 
at the discretion of the SRC (ie, 0.1 mg CC-90009). An intermediate dose of CC-90009 (one 
between the NTD and the last dose level before the NTD) may be evaluated to accurately determine 
the MTD.
Intra-subject dose escalation will not be allowed during the DLT assessment period; however, in 
Cycles ≥ 2, subjects without evidence of disease progression who are tolerating their assigned dose 
of CC-90009 may (at the Investigator’s discretion) escalate to the highest dose level shown to be 
adequately tolerated by at least one cohort of subjects in this study (ie, ≤ 33% of evaluable subjects 
having experienced a DLT at that dose level). If the highest tolerated dose level is Gen 2b CC-
90009, a subject currently enrolled on Gen 1 CC-90009 is permitted to switch to the newer 
formulation. 
Part B-Cohort Expansion
Following completion of dose escalation (Part A), one or more dosing regimens may be selected 
for dose expansion with up to approximately 20 evaluable subjects in each disease indication (R/R 
AML and R/R HR-MDS) at a specified dose level. Subjects with HR-MDS will be enrolled only 
during Part B (Figure 4). Note that the 3.6 mg dose of CC-90009 on Days 1-5 schedule with 
dexamethasone premedication was selected as the Part B dose and schedule in both R/R AML and 
R/R HR-MDS for the dose expansion part of the study (Part B). Due to a high rate of sepsis (75%) 
observed in the initial 8 R/R AML subjects enrolled in Part B at dose level 3.6 mg Days 1-5 with 
dexamethasone premedication, the SRC recommended to close R/R AML and R/R HR-MDS 
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CC-90009-AML-001 Amendment 9
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cohorts receiving CC-90009 at 3.6 mg Days 1-5 for enrollment, and new Part B cohorts will be 
enrolled under an alternative dosing regimen of 2.4 mg Days 1-7 and 3.0 mg Days 1-7, both to be 
evaluated in R/R AML and R/R HR-MDS. The selection of the alternative dose and schedule is 
based primarily on PK and PD analysis and safety and tolerability data. The new Part B cohorts 
will enroll subjects in parallel. Up to 6 subjects per cohort will be initially enrolled as a safety run-
in. The SRC will assess tolerability of the dose and schedule for these initial subjects that 
completed at least one cycle of study treatment based on the Part A stopping criteria (Section 7.2.8)
and recommend further expansion of one or more cohorts. The expanded cohort(s) will be 
monitored for the excess toxicities including sepsis utilizing the non-binding Bayesian stopping 
criterion on a continuous basis (Section 9.9.3). Subjects of R/R AML and R/R HR-MDS enrolled 
in the expansion cohorts may be pooled for analysis of safety, PK, and PD. The SRC will continue 
to review safety and preliminary efficacy data regularly throughout the study and make 
recommendations about study continuation and dose modification, as appropriate.
Study Population
Men and women, 18 years or older, with relapsed or refractory AML or relapsed or refractory 
higher-risk MDS as defined by World Health Organization (WHO) criteria who are not suitable 
for other established therapies, will be enrolled in the study.  
In Part A, only R/R AML subjects will be enrolled. In Part B, one of the initial cohorts will include 
R/R AML subjects, including subjects who relapse after allogeneic HSCT, who are in second or 
later relapse, who are refractory to initial induction or re-induction treatment, who are refractory 
to or relapsed after receiving hypomethylating agents (HMA failure defined as primary 
progression or lack of clinical benefit after a minimum of 6 cycles or unable to tolerate HMA due 
to toxicity), or who relapse within 1 year of initial treatment (excluding those with favorable-risk 
status; see Appendix H).  
In Part B, one of the initial cohorts of R/R HR-MDS subjects will be treated including subjects 
who score > 3.5 points in the Revised International Prognostic Scoring System (IPSS-R) [eg, IPSS-
R intermediate risk (in combination with more than 10% bone marrow blasts or poor or very poor 
IPSS-R cytogenetic risk), IPSS-R high and IPSS-R very high risk] and are not suitable for other 
established therapies (eg, transplant or hypomethylating agent) (Appendix G).
Length of Study
Enrollment is expected to take approximately 62 to 68 months to complete (50 months for dose 
escalation, and approximately 12 to 18 months for expansion). Completion of active treatment and 
post-treatment follow-up is expected to take an additional 6 to 24 months. The entire study is 
expected to last up to approximately 6 to 8 years.
The End of Trial is defined as either the date of the last visit of the last subject to complete the 
post-treatment follow-up, or the date of receipt of the last data point from the last subject that is 
required for primary, secondary, and/or exploratory analysis, as prespecified in the protocol, 
whichever is the later date.
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Study Treatments
Celgene Corporation (Celgene) will supply the investigational product, CC-90009 for IV injection, 
labeled appropriately for investigational use as per the regulations of the relevant country health 
authority. Study drug will be administered as outlined in the Treatment Period section above.
Study treatment may be discontinued if there is evidence of clinically significant disease 
progression (or relapse), unacceptable toxicity or subject/physician decision to withdraw.  Subjects 
may continue to receive study drugs beyond disease progression at the discretion of the 
Investigator in consultation with the Celgene Medical Monitor. 
Overview of Key Efficacy Assessments
The primary efficacy variable is response rate.  
All treated subjects will be included in the efficacy analyses. Leukemia response will be 
determined by the Investigator.  Disease assessment will be based on the International Working 
Group (IWG) Response Criteria in AML (Cheson, 2003; refer to Appendix C). Overall response 
will be determined using the IWG Response Criteria for Myelodysplasia for the HR-MDS cohort
(Cheson, 2006; Appendix F).
A descriptive analysis of evidence of antileukemic activity will be provided based on clinical, 
laboratory, molecular, and cytogenetic assessments by Investigator, which includes assessment of 
bone marrow blast percentage, bone marrow cytogenetics, molecular genetic studies to evaluate 
molecular responses, bone marrow flow cytometry, platelet count, and absolute neutrophil count.  
AML and MDS response criteria will be summarized by best overall response categories: complete 
remission rate (CRR), and objective response rate (ORR). For AML, the ORR includes all 
responses of complete remission (CR) (ie, morphologic CR, cytogenetic CR, molecular CR, 
morphologic CR with incomplete blood recovery, and morphologic CR with partial hematologic 
recovery), morphologic leukemia-free state (MLFS), and partial remission. For MDS, the ORR 
includes all responses (CR, marrow complete remission [mCR], and PR). 
The efficacy variable of focus will be ORR and CRR. Other measures of clinical activity including 
overall survival (OS), relapse-free survival (RFS), progression-free survival (PFS), event-free 
survival (EFS), duration of remission, duration of response, time to transformation (TTT) to AML 
(HR-MDS subjects only) and time to remission/response (TTR) will be summarized.  
Overview of Key Safety Assessments
The safety variables for this study include adverse events, safety clinical laboratory variables, 12-
lead electrocardiograms, Eastern Cooperative Oncology Group Performance Status, left 
ventricular ejection fraction assessments, physical examinations, vital signs, exposure to study 
treatment, assessment of concomitant medications, and pregnancy testing for females of 
childbearing potential.
Overview of Key Pharmacokinetic Assessments
Key plasma PK parameters determined for CC-90009 will include maximum observed 
concentration (Cmax), area under the plasma concentration-time curve from time 0 to 24 hours 
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postdose (AUC24), terminal-phase elimination half-life (t1/2), total plasma clearance (CL), time to 
peak (maximum) plasma concentration (tmax), volume of distribution at the steady state (Vss), 
percent dose excreted in urine as unchanged (Fe) and renal clearance (CLR). Selected PK 
parameters (eg, Cmax, AUC24, t1/2) will be estimated for R- and S-enantiomers of CC-90009 as 
appropriate. Key plasma and urine PK parameters as described above will also be estimated for 
hydroxypropyl-β-cyclodextrin (HPBCD). 
Statistical Methods
Statistical analyses will be performed by dose level (Part A) and cohort (Part B) as needed or 
applicable. All analyses will be descriptive in nature.
All summaries of safety data will be conducted using subjects receiving any CC-90009 (the 
Treated Population). 
The efficacy variables of primary interest are the ORR and CRR. Other preliminary efficacy 
variables including OS, RFS, PFS, event-free survival, duration of remission, duration of response, 
and time to remission/response will be summarized. Efficacy analysis will be repeated for the 
Treated Population and Efficacy Evaluable Population (received a baseline leukemia assessment 
evaluation, at least one cycle of study treatment or at least 80% of scheduled doses in Cycle 1, and 
one on-study leukemia assessment evaluation), with the result using the Treated Population 
considered primary.
All biomarker-related data presentations will be based on treated subjects with at least one 
biomarker assessment, unless specified otherwise. Descriptive statistics will be presented for 
baseline and change from baseline of continuous biomarker endpoints, by dosing regimens and/or 
disease subsets, and overall. 
Exploration of PK, PD, safety and activity relationships will be assessed.  
During the Part A dose escalation, 72 subjects were enrolled. During the Part B dose expansion, 
at least 13 efficacy evaluable subjects with R/R AML will be accrued. If the response rate is 30% 
or more, the probability of seeing no response in the first 13 R/R AML subjects will be less than 
1% (Gehan, 1961). If no responder is observed out of 13 R/R AML subjects, the enrollment for 
this cohort will stop for futility. Otherwise, the cohort will be expanded to up to approximately 20 
evaluable subjects each for R/R AML and R/R HR-MDS of a selected dosing regimen if a 
responder is observed. 
During the Part B dose expansion, a non-binding Bayesian method will be utilized to monitor 
excess toxicities defined as the occurrence of adverse events (AEs) during any cycle that would 
fulfill the DLT criteria specified in Part A or treatment related AEs leading to dose reduction or 
discontinuation or the occurrence of sepsis (Section 9.9.3). The enrollment in the corresponding 
expansion cohort may pause to ensure the posterior probability of excess toxicity rate exceeding 
25% is not more than 70%. After a minimum of 8 subjects have enrolled and taken at least one 
cycle of study treatment for a cohort, the posterior distributions of excess toxicity will be calculated 
on a continuous basis for every subject enrolled (Table 15). If the stopping rule is triggered, the 
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SRC will conduct a comprehensive review of available safety, PK, PD, and efficacy data to make 
continuation decisions.
The study will be conducted in compliance with International Council for Harmonisation of 
Technical Requirements for Pharmaceuticals for Human Use (ICH)/Good Clinical Practice and 
applicable regulatory requirements.
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TABLE OF CONTENTS
TITLE PAGE..............................................................................................................................1
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 9:...............................................7
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 9 ...................................7
PROTOCOL SUMMARY ........................................................................................................10
TABLE OF CONTENTS..........................................................................................................18
LIST OF TABLES....................................................................................................................23
LIST OF FIGURES ..................................................................................................................25
1
INTRODUCTION..................................................................................................26
1.1
Disease Background ...............................................................................................26
1.1.1
Acute Myeloid Leukemia.........................................................................................26
1.1.2
Higher-Risk Myelodysplastic Syndromes ................................................................28
1.2
Compound Background ..........................................................................................29
1.2.1
Nonclinical Pharmacology .....................................................................................29
1.2.1.1
Mechanism of Action ..............................................................................................29
1.2.1.2
In Vitro Pharmacology ...........................................................................................29
1.2.1.3
In Vivo Pharmacology ............................................................................................31
1.2.1.4
In Vivo Pharmacokinetics.......................................................................................31
1.2.2
Nonclinical Toxicology...........................................................................................31
1.2.3
Prior Clinical Experience with CC-90009 ..............................................................33
1.2.3.1
Study CC-90009-AML-001 .....................................................................................33
1.2.4
Safety Monitoring Plan...........................................................................................36
1.3
Rationale ................................................................................................................38
1.3.1
Study Rationale and Purpose..................................................................................38
1.3.2
Rationale for the Study Design................................................................................38
1.3.3
Rationale for Dose, Schedule, and Regimen Selection.............................................39
1.3.4
Rationale for Dose and Dosing Schedule in Part B Dose Expansion.......................41
1.3.5
Rationale for Pharmacodynamics and Potential Predictive Biomarkers..................43
2
STUDY OBJECTIVES AND ENDPOINTS...........................................................45
3
OVERALL STUDY DESIGN ................................................................................47
3.1
Study Design ..........................................................................................................47
3.2
Study Duration for Subjects....................................................................................54
3.3
End of Trial ............................................................................................................54
4
STUDY POPULATION.........................................................................................55
4.1
Number of Subjects ................................................................................................55
4.2
Inclusion Criteria....................................................................................................55
4.3
Exclusion Criteria...................................................................................................57
5
TABLE OF EVENTS.............................................................................................59
6
PROCEDURES......................................................................................................77
6.1
Screening Period.....................................................................................................77
6.1.1
Pregnancy Risk Counseling ....................................................................................79
6.2
Treatment Period ....................................................................................................80
6.2.1
Concomitant Medication and Procedures ...............................................................80
6.2.2
Adverse Event Monitoring ......................................................................................80
6.2.3
Vital Signs and Weight............................................................................................80
6.2.4
Physical Examination and ECOG Performance Status............................................81
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6.2.5
12-Lead Electrocardiograms ..................................................................................81
6.2.6
Left Ventricular Ejection Fraction ..........................................................................82
6.2.7
Pregnancy Testing..................................................................................................82
6.2.8
Clinical Laboratory Tests .......................................................................................82
6.2.9
End of Treatment....................................................................................................83
6.3
Follow-up Period....................................................................................................84
6.3.1
Safety Follow-up.....................................................................................................84
6.3.2
Efficacy Long Term Follow-up ...............................................................................84
6.3.3
Survival Follow-up .................................................................................................84
6.4
Efficacy Assessment...............................................................................................84
6.5
Pharmacokinetics....................................................................................................86
6.5.1
Blood Collection for PK Analysis............................................................................86
6.5.2
Urine Collection for PK Analysis............................................................................88
6.6
Biomarkers, Pharmacodynamics, Pharmacogenomics.............................................88
6.6.1
Pharmacogenomics Sample ....................................................................................88
6.6.2
Pharmacodynamic Biomarker Blood Samples.........................................................88
6.6.3
Pharmacodynamic Biomarker Bone Marrow Samples ............................................90
6.6.4
SARS-CoV-2 Serology Samples...............................................................................91
6.6.5
All Pharmacodynamic and Pharmacogenomics Samples ........................................91
6.7
Additional and Optional Research...........................................................................91
6.7.1
Additional Research ...............................................................................................91
6.7.2
Optional Research..................................................................................................91
6.8
Subject Reported Outcomes....................................................................................91
7
DESCRIPTION OF STUDY TREATMENT..........................................................92
7.1
Description of Investigational Product ....................................................................92
7.1.1
Physical Properties.................................................................................................92
7.1.2
Formulation............................................................................................................92
7.2
Treatment Administration and Schedule .................................................................92
7.2.1
CC-90009 Preparation and Administration ............................................................94
7.2.2
Dose Escalation Criteria ........................................................................................94
7.2.3
Definition of a Subject Evaluable for DLT ..............................................................95
7.2.4
Definition of Non-Tolerated Dose...........................................................................95
7.2.5
Definition of Maximum Tolerated Dose ..................................................................95
7.2.6
Definition of Dose-Limiting Toxicity.......................................................................95
7.2.7
Criteria for Dose Escalation in the Next Cohort of Subjects....................................96
7.2.8
Definition of Stopping Criteria ...............................................................................97
7.2.9
Permitted Study Drug Adjustments .........................................................................97
7.2.10
Criteria for Dose Reduction....................................................................................98
7.2.11
Criteria for Dose Increase ......................................................................................98
7.2.12
Treatment Interruption/Delay for Adverse Events ...................................................98
7.2.13
Management of Select Adverse Events ....................................................................98
7.2.13.1
Prophylaxis and Management of Tumor Lysis Syndrome ........................................98
7.2.13.2
Hypocalcemia.........................................................................................................99
7.2.13.3
Neutropenia and Anemia ......................................................................................100
7.2.13.4
Infection ...............................................................................................................101
7.2.13.5
Pain......................................................................................................................101
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7.2.13.6
Diarrhea...............................................................................................................101
7.2.13.7
Infusion Reactions ................................................................................................101
7.2.13.8
Hypotension..........................................................................................................102
7.2.14
Definition of Overdose..........................................................................................103
7.2.15
Dosage Modifications for Concomitant Use of Strong CYP3A4 Inhibitors in 
Part B Dose Expansion.........................................................................................104
7.3
Method of Treatment Assignment.........................................................................104
7.4
Packaging and Labeling........................................................................................104
7.5
Investigational Product Accountability and Disposal ............................................104
7.6
Investigational Product Compliance......................................................................104
8
CONCOMITANT MEDICATIONS AND PROCEDURES..................................105
8.1
Permitted Concomitant Medications and Procedures.............................................105
8.2
Prohibited Concomitant Medications and Procedures............................................106
8.3
Required Concomitant Medications and Procedures..............................................107
9
STATISTICAL CONSIDERATIONS ..................................................................109
9.1
Overview..............................................................................................................109
9.2
Study Population Definitions ................................................................................109
9.3
Sample Size and Power Considerations.................................................................109
9.4
Background and Demographic Characteristics......................................................110
9.5
Subject Disposition...............................................................................................110
9.6
Efficacy Analysis..................................................................................................110
9.6.1
Complete Remission Rate and Objective Response Rate........................................110
9.6.2
Time to Event Variables........................................................................................111
9.7
Safety Analysis.....................................................................................................111
9.8
Interim Analysis ...................................................................................................112
9.9
Other Topics.........................................................................................................112
9.9.1
Assessment of Pharmacokinetics...........................................................................112
9.9.2
Assessment of Pharmacodynamics........................................................................112
9.9.3
Stopping Rules Regarding Toxicity in Part B Dose Expansion ..............................113
10
ADVERSE EVENTS............................................................................................115
10.1
Monitoring, Recording and Reporting of Adverse Events .....................................115
10.2
Evaluation of Adverse Events...............................................................................115
10.2.1
Seriousness...........................................................................................................116
10.2.2
Severity/Intensity ..................................................................................................117
10.2.3
Causality ..............................................................................................................117
10.2.4
Duration...............................................................................................................118
10.2.5
Action Taken.........................................................................................................118
10.2.6
Outcome ...............................................................................................................118
10.3
Abnormal Laboratory Values................................................................................118
10.4
Pregnancy.............................................................................................................119
10.4.1
Females of Childbearing Potential: ......................................................................119
10.4.2
Male Subjects .......................................................................................................119
10.5
Reporting of Serious Adverse Events....................................................................120
10.6
Expedited Reporting of Adverse Events................................................................120
11
DISCONTINUATIONS .......................................................................................122
11.1
Treatment Discontinuation....................................................................................122
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11.2
Study Discontinuation ..........................................................................................122
12
EMERGENCY PROCEDURES...........................................................................123
12.1
Emergency Contact...............................................................................................123
12.2
Emergency Identification of Investigational Products ...........................................123
13
REGULATORY CONSIDERATIONS.................................................................124
13.1
Good Clinical Practice..........................................................................................124
13.2
Investigator Responsibilities .................................................................................124
13.3
Subject Information and Informed Consent...........................................................124
13.4
Confidentiality......................................................................................................125
13.5
Protocol Amendments...........................................................................................125
13.6
Institutional Review Board/Independent Ethics Committee Review and 
Approval ..............................................................................................................125
13.7
Ongoing Information for Institutional Review Board/ Ethics Committee ..............126
13.8
Termination of the Study ......................................................................................126
14
DATA HANDLING AND RECORDKEEPING...................................................127
14.1
Data/Documents ...................................................................................................127
14.2
Data Management.................................................................................................127
14.3
Record Retention..................................................................................................127
15
QUALITY CONTROL AND QUALITY ASSURANCE......................................129
15.1
Study Monitoring and Source Data Verification....................................................129
15.2
Audits and Inspections..........................................................................................129
15.3
Investigational Medicinal Product Quality Issues..................................................129
16
PUBLICATIONS .................................................................................................131
17
REFERENCES.....................................................................................................132
18
APPENDICES......................................................................................................136
Appendix A:
Table of Abbreviations .........................................................................136
Appendix B:
The World Health Organization (WHO) Classification of Acute 
Myeloid Leukemia (AML)....................................................................................141
Appendix C:
Response Criteria for Acute Myeloid Leukemia ...................................142
Appendix D:
Performance Status Criteria ..................................................................143
Appendix E:
The World Health Organization (WHO) Classification of the 
Myelodysplastic Syndromes .................................................................................144
Appendix F:
International Working Group (IWG) Response Criteria for 
Myelodysplasia.....................................................................................................145
Appendix G:
Revised International Prognostic Scoring System for MDS..................147
Appendix H:
Risk Status Based on Cytogenetics for Acute Myeloid Leukemia .........149
Appendix I:
Tumor Lysis Syndrome Prophylaxis Recommendations .......................150
Appendix J:
Recommendations for Management of Treatment-Induced 
Diarrhea 152
Appendix K:
Part A Table of Events for D1-3/D8-10 Dosing Schedule .....................153
Appendix L:
CC-90009 Pregnancy Prevention Plan ..................................................160
Appendix M:
Part A Table of Events for D1-7 Dosing Schedule ................................161
Appendix N:
Part B Table of Events for D1-7 Dosing Schedule ................................170
Appendix O:
Part A Table of Events for D1-10 Dosing Schedule ..............................180
Appendix P:
The Operating Characteristics of the Proposed Bayesian Safety 
Monitoring Plan....................................................................................................190
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Appendix Q:
Blood Collection for PK Analysis.........................................................191
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LIST OF TABLES
Table 1:
Starting Doses in Humans Based on the Doses Tested in the 28-
day Monkey Studies with CC-90009 ......................................................41
Table 2:
Study Objectives ....................................................................................45
Table 3:
Study Endpoints .....................................................................................46
Table 4:
Table of Events for Cycle 1 in Part A (D1-5 Schedule)...........................59
Table 5:
Table of Events for Cycles ≥ 2 in Part A (D1-5 Schedule), End of 
Treatment Visit, and Follow-up Period ...................................................64
Table 6:
Table of Events for Cycle 1 in Part B (D1-5 Schedule) ...........................68
Table 7:
Table of Events for Cycles ≥ 2 in Part B (D1-5 Schedule), End of 
Treatment Visit, and Follow-up Period ...................................................73
Table 8:
Blood Pharmacokinetic Sampling Schedule in Part B: 2.4 and 3.0 
mg Days 1-7 Schedule............................................................................87
Table 9:
Sample Collection of Blood for Pharmacodynamic Biomarkers on 
D1-5 Schedule and Alternative Schedules with up to 10 
consecutive dosing days (eg, D1-7 and D1-10) for Part A or Part B........89
Table 10:
Sample Collection of Blood for Pharmacodynamic Biomarkers 
using the Alternate D1-3/D8-10 Schedule for Part A or Part B................90
Table 11:
Management of Hypocalcemia .............................................................100
Table 12:
Modified Grading for Hypotension for CC-90009 ................................103
Table 13:
High-dose Vasopressors (all doses are required for ≥ 3 hours)..............103
Table 14:
Confidence Interval for 20% and 30% Response Rate for Different 
Scenarios of Sample Size (Wilson score interval) .................................110
Table 15:
Stop Boundaries Based on Stopping Criteria for Each Expansion 
Cohort ..................................................................................................113
Table 16:
Abbreviations and Specialist Terms......................................................136
Table 17:
WHO classification of AML.................................................................141
Table 18:
Hematologic Response According to IWG Criteria for AML................142
Table 19:
Eastern Cooperative Oncology Group (ECOG) Performance Status 
(PS)......................................................................................................143
Table 20:
WHO classifications for MDS ..............................................................144
Table 21:
Modified IWG Response Criteria for MDS...........................................145
Table 22:
RBC and Platelet Transfusion Independence ........................................146
Table 23:
IPSS-R Cytogenetic Risk Groups .........................................................147
Table 24:
IPSS-R Prognostic Score Values...........................................................147
Table 25:
IPSS-R Prognostic Risk Categories/Scores...........................................147
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Table 26:
IPSS-R: Prognostic Risk Category Clinical Outcomes..........................148
Table 27:
Risk Groups..........................................................................................149
Table 28:
Tumor Lysis Syndrome (TLS) Prophylaxis Recommendations 
Based on TLS Risk...............................................................................150
Table 29:
Cairo-Bishop Definition of Laboratory Tumor Lysis Syndrome............150
Table 30:
Cairo-Bishop Grading System for Tumor Lysis Syndrome ...................151
Table 31:
Table of Events for Part A (D1-3/D8-10 Schedule) of Cycle 1..............153
Table 32:
Table of Events for Part A (D1-3/D8-10 Schedule) of Cycle ≥ 2...........157
Table 33:
Table of Events for Part A (D1-7 Schedule) of Cycle 1.........................161
Table 34:
Table of Events for Part A (D1-7 Schedule) of Cycles ≥ 2 ....................166
Table 35:
Table of Events for Part B (D1-7 Schedule) of Cycle 1.........................170
Table 36:
Table of Events for Part B (D1-7 Schedule) of Cycles ≥ 2 ....................175
Table 37:
Table of Events for Part A (D1-10 Schedule) of Cycle 1.......................180
Table 38:
Table of Events for Part A (D1-10 Schedule) of Cycles ≥ 2 ..................185
Table 39:
The Operating Characteristics for Bayesian Monitor Plan.....................190
Table 40:
Blood Pharmacokinetic Sampling Schedule for Cycle 1 in Part A 
for D1-5 and Alternative Schedules with up to 10 consecutive 
dosing days (eg, D1-7 and D1-10) ........................................................191
Table 41:
Blood Pharmacokinetic Sampling Schedule for Cycle 2 in Part A 
for D1-5 and Alternative Schedules with up to 10 consecutive 
dosing days (eg, D1-7 and D1-10) ........................................................192
Table 42:
Blood Pharmacokinetic Sampling Schedule for Cycle 1 in Part A 
for D1-3/D8-10 Schedule......................................................................192
Table 43:
Blood Pharmacokinetic Sampling Schedule for Cycle 2 in Part A 
for D1-3/D8-10 Schedule......................................................................193
Table 44:
Blood Pharmacokinetic Sampling Schedule in Part B: 3.6 mg Day 
1-5 Schedule.........................................................................................193
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LIST OF FIGURES
Figure 1:
Study Schema for Dose-Limiting Toxicity Window in Part A 
(Dose Escalation) ...................................................................................52
Figure 2:
Sample Dose Escalation Schemes for Part A with an NTD of 8.1 
mg..........................................................................................................53
Figure 3:
Sample Dose Escalation with or without a Schedule Change ..................54
Figure 4:
High Level Study Design........................................................................54
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1
INTRODUCTION
CC-90009 is a small molecule being developed for the treatment of acute myeloid leukemia 
(AML) and higher-risk myelodysplastic syndromes (MDS) and is a member of a class of agents 
identified as cereblon (CRBN) E3 ligase modulating drugs.  CC-90009 was strongly 
antiproliferative in the majority of AML cell lines tested (10 out of 11) as well as in primary AML 
patient samples and exerted its effects through rapid induction of apoptosis.  CC-90009 also 
reduced tumor cell numbers in bone marrow in the HL-60 intravenous (IV) xenograft model of 
AML. CC-90009 had potent antiproliferative and cytotoxic activity against both an MDS cell line 
and HR-MDS patient derived bone marrow cells assayed ex vivo.  The potent antiproliferative 
activity of CC-90009 is cereblon-dependent and entails induction of an unfolded protein response 
(UPR).  Cereblon is the substrate receptor component of the cullin ring ligase (CRL)4/cereblon/E3-
ubiquitin ligase complex that recruits specific proteins to the complex for ubiquitination and 
subsequent proteasomal degradation.
1.1
Disease Background
1.1.1
Acute Myeloid Leukemia
Acute myeloid leukemia is the most commonly reported type of acute leukemia in adults in the 
United States (US). Based on the American Cancer Society’s estimates, approximately
20,830 people will be diagnosed with AML in 2015 in the US and 10,460 patients will die from 
the disease (American Cancer Society, 2015).  The median age at diagnosis is approximately 
67 years.
Acute myeloid leukemia can arise de novo, be secondary to previous cytotoxic chemotherapy, or 
arise through transformation of existing myelodysplasia.  Therapy-related AML arising from 
exposure to environmental toxins, cytotoxic drugs, or radiation currently accounts for about 5% to 
10% of all cases of AML (Leone, 1999).  It is estimated that 35% to 40% of patients with 
myelodysplastic syndromes will go on to develop AML, with the disease often refractory to current 
therapy (Silverman, 2000).  Preexisting myelodysplastic or myeloproliferative disorders are 
common in older patients with AML, occurring in 24% to 40% of cases (Gajewski, 1989).  Patients 
with secondary AML due to prior hematologic disease have a lesser response to therapy than those 
with de novo disease.  In the series from the Southwest Oncology Group, for example, the complete 
remission (CR) rates were 24% and 52%, respectively (Leith, 1997, Gajewski, 1989.
The usual treatment of AML is divided into two phases: induction of remission and consolidation 
therapy.  For more than 30 years, the combination of cytarabine and an anthracycline has been the 
mainstay of treatments to induce remission (Lowenberg, 1999; Tallman, 2005).  The remission 
induction therapy in leukemia is designed to produce the rapid restoration of normal bone marrow 
function.  A common induction regimen consists of cytarabine, 100 mg/m2/day for 7 days 
combined with daunorubicin 45-60 mg/m2/day for 3 days, often referred to as the “7+3 protocol.”  
With the combination of cytarabine and daunorubicin or their analogues, a CR, conventionally 
defined morphologically by the presence of < 5% blasts in the bone marrow together with the 
recovery of peripheral-blood absolute neutrophil and platelet counts, can be achieved in up to 70% 
to 80% of adults with de novo AML who are < 60 years of age (Lowenberg, 1999; Tallman, 2005).  
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If CR is achieved, there are 3 basic treatment choices for post-remission therapy: additional 
chemotherapy, stem cell transplantation from a donor (allogeneic stem cell transplantation), or 
stem cell transplantation using the patient's own stem cells (autologous stem cell transplantation).  
For post-remission chemotherapy, the same chemotherapy regimen used for remission induction 
or a higher dose regimen of cytarabine is often repeated for one or more cycles, referred to as 
consolidation chemotherapy.  When several courses of consolidation are given, survival rates at 2-
3 years are 35% to 50% for young to middle-age adults who have achieved CR (Milligan, 2006).  
However, consolidation or post-remission chemotherapy for elderly patients with AML has not 
been proven beneficial.
Importantly, AML is mostly a disease of older individuals with a median age at diagnosis of 
approximately 67 years.  Older patients with AML have significant comorbidities, more 
unfavorable cytogenetic abnormalities, a poorer performance status, and a higher incidence of 
AML arising from MDS.  Moreover, older patients are more likely to have increased multidrug 
resistance to chemotherapy, inability to tolerate intensive chemotherapy, which may be responsible 
in large part for the poor outcomes observed in older-aged subgroups.  In elderly AML patients, 
defined as older than 60 years, conventional cytotoxic intensive chemotherapy has been associated 
with CR rates of approximately 45%, considerably lower than in younger patients (Jabbour, 2006).  
Unfortunately, the duration of remission is shorter, the early treatment-related mortality is high, 
approximately 30% to 50% (Jabbour, 2006), which in part explains a median survival time 
between 7 to 12 months (Dombret, 2008; Burnett, 2007).  
Given the poor overall outcome and high treatment-related mortality in older AML patients, some 
physicians do not pursue aggressive induction therapy, opting for less aggressive therapies.  
Treatment options are few for patients who choose not to receive intensive chemotherapy or are 
considered ineligible (unfit) to receive intensive chemotherapy by their physician.  Patients 
considered ineligible for intensive chemotherapy are generally patients older than 75 years or those 
60 to 75 years old with significant comorbidities, poor performance status, or with complex 
cytogenetic abnormalities (NCCN 2017a; Milligan, 2006).  Treatment options for these patients 
include low-intensity therapies such as low-dose cytarabine or supportive care only.  In a Medical 
Research Council (MRC) AML14 study, low-dose cytarabine (20 mg twice daily for 10 days) was 
compared to best supportive care including hydroxyurea in patients with AML who were greater 
than 65 years of age and considered ineligible for intensive chemotherapy by the Investigator 
(Burnett, 2007).  No specific criteria were used to determine the patient’s eligibility for 
chemotherapy other than those patients at least 70 years old who had to have a documented 
comorbidity that precluded chemotherapy.  The low-dose cytarabine group demonstrated a higher 
CRR (18%) compared to hydroxyurea (1%).  Overall survival was also significantly better in the 
low-dose cytarabine group, but only approximately 50% of the patients were alive at 4 months and 
25% were alive at 1 year (Burnett, 2007).  In a retrospective analysis of 36 AML studies with a 
median age of 70 years, patients receiving low-intensity therapies or best supportive care had a 
median overall survival of approximately 3 months and 2 months, respectively (Deschler, 2006). 
Despite a survival benefit with the use of less intensive chemotherapy such as low-dose cytarabine 
in this elderly AML population, the outcome remains unsatisfactory. 
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1.1.2
Higher-Risk Myelodysplastic Syndromes
Myelodysplastic syndromes (MDS) is an umbrella term for a heterogeneous collection of 
hematopoietic stem cell disorders primarily affecting older adults. It is estimated that between 2 
and 4 cases per 100,000 persons per year are diagnosed with MDS. The elderly are particularly 
vulnerable with annual incidence rates between 15 and 50 cases per 100,000 persons per year 
(Steensma, 2003). The prognosis depends on the individual’s risk factors, with a median survival 
ranging from 5.3 years in low-risk patients to 1.6 and 0.8 years in high- or very high-risk patients 
(Greenberg, 2012). 
Myelodysplastic syndromes is typically characterized by ineffective hematopoiesis in the bone 
marrow (BM) and peripheral blood cytopenias that manifest clinically as anemia, neutropenia, 
and/or thrombocytopenia of variable frequency and severity. Anemia is the most frequent 
laboratory finding and it often progresses to red blood cell (RBC) transfusion dependence. Other 
less common presenting clinical features related to the cytopenias are an increased risk of infection 
and/or hemorrhage and a propensity to progress to acute myeloid leukemia (AML) (Catenacci,
2005). 
For certain subtypes of MDS, excess blast cells are present (Bennett, 1982).  Progress in 
understanding the pathobiology of MDS has evolved rapidly, as have an increasing number of 
myeloablative and supportive care strategies.  The mainstay of therapy has been supportive care, 
which includes the use of red cell or platelet transfusions, treatment of infections, and the use of 
epoetin alfa or myeloid growth factors when needed (NCCN, 2017b; Silverman, 2000; Lübbert, 
2000).  Vidaza (azacitidine) has been shown to increase overall survival in patients with higher-risk 
myelodysplastic syndromes relative to conventional care but is not curative (Fenaux, 2009).  Bone
marrow transplantation has been effective both in patients under the age of 50 and in those older 
than 50 who are in good health.  However, this approach has limited value, since most patients 
with MDS are older than 65 years of age and have significant comorbidities (NCCN, 2017b; 
Silverman, 2000). 
Major MDS prognostic risk scoring systems and predictors have been developed over the years. 
Changes in risk of mortality and of leukemic transformation over time were recently compared in 
a multicenter retrospective study which included 7212 primary untreated MDS patients 
(Pfeilstöcker, 2016). The analysis of hazards regarding mortality and AML transformation risk 
suggested a division into lower- and higher-risk MDS based on the IPSS-R (Greenberg, 2012) 
cutoff of 3.5 points. For this study, higher-risk MDS will be defined as patients with > 3.5 points 
in the IPSS-R system (Greenberg, 2012, Pfeilstöcker, 2016). This includes all patients in the High 
(> 4.5 – 6) and Very High (> 6) IPSS-R risk groups as well as a sub-population of those in the 
Intermediate (> 3-4.5) category. High and Very High risk groups had a median survival of 1.6 and 
0.8 years respectively, and the subpopulations with poor and very poor cytogenetics with median 
survival of 1.5 and 0.7 years respectively or a blast count > 10% (survival 1.3 years) (Greenberg, 
2012).  Relapsed or refractory higher-risk MDS patients are a high-unmet need population for 
which there is no standard of care and novel therapies are needed.
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1.2
Compound Background
Please refer to the CC-90009 Investigator’s Brochure (IB, CC-90009 IB) for detailed information 
concerning the available pharmacology, toxicology, and drug metabolism of the investigational 
product (IP).
1.2.1
Nonclinical Pharmacology
1.2.1.1
Mechanism of Action
CC-90009 is a potent antitumor agent in vitro demonstrating strong antiproliferative activity 
against AML cell lines. CC-90009 inhibited cell growth in 10 of the 11 cell lines in a representative 
panel of AML cell lines that included a range of common oncogenic AML mutations (IC50 = 3 to 
75 nM). The antiproliferative activity of CC-90009 is achieved through rapid induction of 
apoptosis. The mechanism of action of CC-90009 entails induction of an UPR. The potent 
antiproliferative activity of CC-90009 is CBRN-dependent, as CC-90009 did not inhibit growth in 
CBRN-deficient constructs of sensitive AML cell lines. Cereblon is the substrate receptor
component of the CRL4/CBRN/E3–ubiquitin ligase complex that recruits specific proteins to the 
complex for ubiquitination and subsequent proteasomal degradation. CC-90009-induced CBRN
substrates and markers of UPR will be used as pharmacodynamics (PD) mechanism markers.
1.2.1.2
In Vitro Pharmacology
CC-90009 had potent anti-proliferative and cytotoxic activity against both an MDS cell line (sub 
nM IC50) and HR-MDS patient derived bone marrow cells assayed in ex vivo. CC-90009 strongly 
inhibits both proliferation and self-renewal activity of bone marrow cells derived from HR-MDS 
patients, compared to age matched normal donor controls, suggesting a therapeutic index may be 
achieved in HR-MDS.
Effect on Hematopoiesis in Normal Donor Bone Marrow Samples
The effect of CC-90009 on hematopoietic progenitors was evaluated using colony forming assays 
in bone marrow cluster of differentiation (CD)34+ cells derived from four individual healthy 
donors.
Inhibition of granulo-monocytic progenitors (half-maximal inhibitory concentration 
[IC50] = 82 to 135 nM) and erythroid progenitors (IC50 = 32 to 131 nM) derived from normal bone 
marrow was observed. At 8 hours exposure, the effect on hematopoietic progenitors was reduced 
in intensity relative to continuous exposure to CC-90009 for 14 days and, at 2 or 4 hours exposure, 
the inhibitory effect of CC-90009 was absent. The data suggest that the impairment of growth of 
hematopoietic progenitors by CC-90009 may be effectively managed if dose and time of exposure 
are reduced.
Effects of CC-90009 on neutrophil maturation in normal bone marrow samples were evaluated by 
two-dimensional cultivation of progenitors followed by assessment of cell differentiation and 
apoptosis. There was no reduction in viability in cultures exposed to 0.03 to 30 nM CC-90009 for 
8 hours or to ≤ 3 nM CC-90009 for 24 or 72 hours. However, there was reduction in viability in 
cells exposed to 30 nM CC-90009 for 24 or 72 hours. Removal of CC-90009 after 72 hours and 
subsequent incubation for the remainder of the 14-day differentiation period led to improvement 
in viability. Surviving cells were able to proliferate and fully mature to normal neutrophils.
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Antitumor Activity in AML versus Normal Bone Marrow Samples
The antitumor activity of CC-90009 in 4 AML patient bone marrow samples was explored in a 
semi-solid culture system and compared with the results for normal bone marrow samples.
CC-90009 did not demonstrate greater activity against progenitors in bone marrow of AML 
patients versus normal donors. The antiproliferative activity of CC-90009 against hematopoietic 
progenitors in AML patient bone marrow samples (IC50 of 7.8 to 94 nM) was broadly similar to 
that in normal bone marrow samples (IC50 = 8.6 to 10.7 nM).
The antitumor activity of CC-90009 in bone marrow aspirates derived from 30 AML patients 
during patient diagnosis was evaluated in a test system ex vivo that did not separate the samples 
into constituent cells and thereby retained the microenvironment of bone. CC-90009 demonstrated 
potent activity in 26 of the 30 AML patient samples (average EC50 = 21 nM [range 2 to 160 nM]
across all 3 time points in the 26 sensitive AML patient samples). Leukemic cell killing was rapid 
and efficient in the sensitive patient samples in that, on average, > 82% of leukemic cells were 
depleted by 24 hours, > 92% by 48 hours, and > 98% by 96 hours.  Furthermore, in patient samples 
where sufficient normal lymphocytes could be counted, CC-90009 exhibited only modest 
antiproliferative activity against the normal cells (maximum possible effect [Emax] averaged 46% 
to 76% from 24 to 96 hours). CC-90009 displayed a differential potency between leukemic and 
normal hematopoietic cells of 2- to 5-fold across the three time points.
The results indicate that addition of CC-90009 to ex vivo cultures of healthy donor bone marrows 
resulted in decreased/delayed formation of granulo-monocytic and erythroid colonies by inducing 
cell growth delay or arrest without reducing survival of the hematopoietic stem cells or 
hematopoietic progenitors for 8 hours.  The findings suggest the possibility of devising dosing 
strategies for elimination of AML cells that spare normal hematopoietic stem/progenitor cells and 
permit neutropenia to be reversed.
Therapeutic Window
The findings of several different investigations point to the selectivity of CC-90009 for 
antiproliferative activity in AML cells versus normal cells. CC-90009 demonstrated greater 
antiproliferative activity in vitro in sensitive AML cell lines than in activated, rapidly proliferating 
peripheral blood mononuclear cells (PBMCs) or in THLE-2 cells, a non-tumorigenic immortalized 
human hepatocyte cell line (IC50 = 5.5 μM). The induction of apoptosis by CC-90009 was 3- to 7-
fold greater in a sensitive AML cell line than in PBMCs. CC-90009 demonstrated potent activity 
that entailed rapid and efficient leukemic cell killing in 26 of 30 AML patient bone marrow 
samples ex vivo while exhibiting only modest antiproliferative activity against the normal cells in 
the same samples. Overall, the results suggest the potential of a therapeutic window for CC-90009 
in AML patients.
CC-90009 incubation of AML cell lines in vitro and AML patient-derived bone marrow 
mononuclear cells ex vivo resulted in significant increases in IL-1 proteins that could be blocked 
by inhibiting apoptosis. This suggested that CC-90009-induced apoptosis may lead to release of 
IL-1 and result in systemic cytokine exposure and hypotension in patients. Dexamethasone (but 
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not indomethacin or celecoxib) significantly reduced IL-1b levels induced by CC-90009 in AML 
cell lines.
1.2.1.3
In Vivo Pharmacology
CC-90009 antitumor activity was assessed in the HL-60 xenograft model of AML. Although an 
initial study did not result in evidence of improved survival in CC-90009-treated animals, a second 
study in which bone marrow was examined did reveal a substantial reduction in numbers of tumor 
cells in bone marrow of CC-90009-treated animals with two dosing schedules [5 mg/kg twice a 
day (BID) x 5 days or 2.5 mg/kg BID x 10 days].  These data indicate that the two dosing schedules 
can achieve approximately equivalent efficacy.  
1.2.1.4
In Vivo Pharmacokinetics
In animal models, CC-90009 demonstrated low clearance and extensive distribution.  Minimal 
(rat) or no (monkey) sex differences in pharmacokinetics (PK) or toxicokinetics (TK) were noted 
across studies.  Overall, CC-90009 showed acceptable PK properties in single-dose and 
repeat-dose TK studies.
CC-90009 was metabolized primarily via non-enzymatic (hydrolysis) and enzymatic pathways.  
Although there were quantitative interspecies differences in the formation of metabolites, 
qualitatively all metabolites formed in human hepatocytes were also formed in rat and/or monkey 
hepatocytes, the species used for preclinical safety testing.  
CC-90009 (up to 2.5 µM) did not cause inhibition and induction of cytochrome P450 (CYP)
enzymes in in vitro studies except for moderate inhibition of CYP2C9 (41% at 2.5 µM) and 
CYP2C19 (IC50 = 1.53 µM). Even though CC-90009 is not anticipated to cause drug interactions 
when administered with CYP2C9 and CYP2C19 substrates at clinically relevant concentrations, 
caution should be used with narrow therapeutic index substrates such as warfarin, consistent with 
general clinical practice.
In humans, using the PK parameters of CC-90009 in monkeys and single species allometric 
scaling, CC-90009 is predicted to have low clearance (18.9 L/hr, up to approximately one-fourth 
liver blood flow) and high volume of distribution (1.44 L/kg, up to approximately 3-fold total body 
water volume).
1.2.2
Nonclinical Toxicology
The toxicity of CC-90009 has been characterized in a core battery of repeat-dose toxicity studies 
in rats and monkeys using intravenous bolus injection as the route of administration and in the in 
vitro genotoxicity studies.  
In the CC-90009 pivotal 28-day (with a 28-day recovery period) intravenous rat toxicity study, 
there were no CC-90009-related effects noted up to the highest dose of 5 mg/kg/day, which was 
the maximum feasible dose that could be given to rats based on the tolerability of the vehicle.  
Based on the absence of CC-90009-related findings, the severely toxic dose in 10% (STD10) of 
rats for this study was considered to be greater than 5.0 mg/kg/day and the no observable effect 
level (NOEL) was determined to be 5.0 mg/kg/day, the top dose administered, corresponding to a 
combined-sex mean plasma concentration at 5 minutes postdose (C5min) of 5420 ng/mL and the 
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combined-sex mean area under the plasma concentration-time curve calculated to the last 
observable concentration at time t (AUCt) of 8050 ng•h/mL on Day 28. These C5min and AUCt
were 32- and 22-fold greater than those obtained at the highest dose of 0.3 mg/kg/day tested in the 
pivotal 28-day monkey study.
In the CC-90009 28-day (with a 28-day recovery period) intravenous monkey toxicity study, 
adverse effects on clinical condition (including inappetence, decreased activity, tremors, and 
unsteady movement) were observed in males and females administered 0.1 mg/kg/day for 28 days
and in females administered 0.3 mg/kg/day on Days 1 to 5 and 15 to 19. Decreased sternal bone 
marrow cellularity was observed in males and females dosed at ≥ 0.1 mg/kg/day and was reflected 
in decreases in reticulocyte counts. The severity of bone marrow hypocellularity ranged from 
minimal to marked at 0.1 mg/kg/day for 28 days and from slight to moderate at 0.3 mg/kg/day for 
a total of 10 days. Based on the marked severity of bone marrow hypocellularity in one male at 
0.1 mg/kg/day and a lack of complete recovery in one female at 0.3 mg/kg/day, these doses were 
considered severely toxic doses to the monkeys. Therefore, the no observed adverse effect level 
(NOAEL) and the highest non-severely toxic dose (HNSTD) was 0.03 mg/kg/day, corresponding 
to a mean C5min of 16.7 ng/mL and a mean AUCt of 30.6 ng∙hr/mL for combined sexes on Day 28. 
Decreased total calcium (Ca) levels were noted in the pivotal 28-day monkey study when animals 
were treated at 0.1 mg/kg/day for 28 days or at 0.3 mg/kg/day on Days 1 to 5 and Days 15 to 19.  
When compared to pretest values, mean total Ca levels were 11% and 17% lower on Day 27 in 
males and females treated at 0.1 mg/kg/day, respectively.  In males and females treated at 
0.3 mg/kg/day, mean values were 19% and 15% lower, respectively, on Day 18 (4thday of the 
second 5-day cycle). These decreases were not considered adverse, and were, at least in part, due 
to decreases in total protein, albumin, and globulin levels observed in these dosage groups.  
However, in an earlier exploratory study, an approximately 50% decrease in total serum Ca level 
was observed when cynomolgus monkeys were dosed at 0.3 mg/kg/day for 7 days. In addition, 
more severe clinical signs of ataxia, hunched posture, tremors, tonic convulsions, dilated pupil(s), 
lateral recumbency, clenched fists, and inappetence were observed in these animals.  In order to 
investigate the relationship of these signs to a reduction in serum calcium, another monkey study 
was conducted with animals dosed at 0.3 mg/kg/day for up to 14 days, with or without calcium
and vitamin D supplementation, with a 14-day recovery period. The purposes of this study were 
to measure ionized Ca level, to investigate effect of calcium and vitamin D supplementation on 
serum Ca level and clinical condition of monkeys during CC-90009 treatment, and to assess 
reversibility of clinical effects when dosing was terminated.  
The data from this study demonstrate a strong correlation between clinical signs and calcium 
levels.  All CC-90009 treated animals without calcium and vitamin D supplementation tolerated 5 
daily doses of 0.3 mg/kg with the exception of one male who received only 4 doses and needed IV 
calcium supplementation to recover. A drop in calcium level was first observed on Day 3 of dosing. 
During the recovery period for animals that received 5 days of treatment, the reversibility of 
calcium level and clinical signs was observed within 2 days after cessation of dosing.  These 
animals did not need calcium supplementation for their recovery. 
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In the group of animals with calcium and vitamin D supplementation (started prior to CC-90009 
dosing), improved tolerability with significantly prolonged duration of dosing (range = 6 to 
13 days with mean duration of 10 days; 4/10 animals received 13 doses) were observed. In these 
animals, the drop in calcium level was also first observed on Day 3, but the decreases were mild. 
Clinical signs were similar but with a later onset and decreased severity. 
These data from multiple monkey studies showed that the decreases in serum Ca level were dose-
and duration-dependent, and the magnitude of reduction became adverse only when a dose of 0.3 
mg/kg/day was given longer than 5 days without supplementation. At the HNSTD and NOAEL of 
0.03 mg/kg/day in the pivotal monkey study, there was no change in total serum Ca at the end of 
28 days of continuous daily treatment.  Furthermore, in all 3 dose groups in the 28-day Good 
Laboratory Practice (GLP) toxicity study, animals did not exhibit severe clinical signs as those 
seen in the second GLP monkey study when a dose of 0.3 mg/kg/day was administered for longer 
than 5 days. Therefore, data from the investigative study, though provided more information, did 
not change the overall conclusions of the 28-day monkey study. All of these data have been taken 
into consideration for clinical trial design and management of potential hypocalcemic effect of 
CC-90009 in humans.
CC-90009 was not mutagenic when tested in the bacterial reverse mutation assay. In the in vitro 
chromosomal aberrations assay using the Chinese Hamster Ovary (CHO) cells, CC-90009 was 
positive for the induction of structural and negative for the induction of numerical chromosome 
aberrations under the non-activated treatment condition. CC-90009 was negative for the induction 
of structural and numerical chromosome aberrations under the S9-activated treatment condition.
Please refer to the most current version of CC-90009 IB for the latest, detailed clinical information 
concerning pharmacology, toxicology, drug metabolism, patient outcomes, and the adverse event 
(AE) profile of CC-90009.
1.2.3
Prior Clinical Experience with CC-90009
A summary of clinical experience with CC-90009 as of 17 Feb 2021 is provided in the CC-90009 
Investigator’s Brochure (IB), Edition 7.0 (CC-90009 IB, 2021), based on two ongoing studies, CC-
90009-AML-001 (a first-in-human study of CC-90009 monotherapy in subjects with R/R AML or 
R/R HR-MDS) and CC-90009-AML-002 (a Phase 1b study of CC-90009 in combination with 
anti-leukemia agents in subjects with AML). A planned study of CC-90009-CP-001 is a clinical 
pharmacology study in healthy male subjects. Most extensive clinical information comes from the 
CC-90009-AML-001 study. Please refer to the most current version of CC-90009 IB for the latest, 
detailed clinical information concerning pharmacology, toxicology, drug metabolism, patient
outcomes, and the adverse event (AE) profile of CC-90009.
1.2.3.1
Study CC-90009-AML-001
Enrollment of subjects in Part A Dose Escalation of the study has been completed and a total of 
72 subjects were treated. (One subject, in the 3.6 mg with dexamethasone premedication cohort, 
was reenrolled under a new subject number after discontinuing from study and subsequently 
relapsing after 8 months of complete remission. The subject’s two subject numbers were 
consolidated, and they were counted only once.) All treated subjects had R/R AML. To date, 4 
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dosing schedules of CC-90009 have been explored; once daily dosing on Days 1-5 of a 28-day 
cycle (0.3 mg to 4.5 mg), Days 1-7 of a 28-day cycle (3.6 mg), Days 1-10 of a 28-day cycle (3.0 
mg), and Days 1-3 and 8-10 of a 28-day schedule (3.0 and 3.6 mg). Dose levels of 3.6 mg and 
above and the 3.0 mg dose level on the Days 1-10 schedule included premedication with 
dexamethasone for subjects enrolling starting with Protocol Amendment 5. As of 01 Apr 2021, 
enrollment in Part A of the study has been completed. After a review of Part A data, the SRC 
recommended that CC-90009 be dosed at 3.6 mg on Days 1–5 with dexamethasone premedication 
in Part B Dose Expansion in both R/R AML and R/R HR-MDS. After review of initial data from 
Part B Dose Expansion with an observation of a higher rate of sepsis in the Part B R/R AML cohort 
as compared to R/R AML cohorts in Part A, the SRC recommended to close R/R AML and R/R 
HR-MDS cohorts receiving CC-90009 at 3.6 mg Days 1–5 for enrollment, and two new dose levels
(2.4 mg and 3.0 mg on Days 1-7) were recommended to be expanded as part of a dose optimization 
and sepsis mitigation strategy.
As of the 13 Aug 2021 cutoff date, preliminary data are available for 80 subjects with R/R AML 
and 2 subjects with R/R HR-MDS. Of the 82 subjects treated with CC-90009, 79 (96.3%) had 
discontinued from treatment and out of these, 76 (92.7%) had discontinued from the study. The 
most common reason for treatment discontinuation was progressive disease in 24 (29.3%) subjects. 
The most common reason for study discontinuation was death in 67 (81.7%) subjects. 
The median age of all enrolled subjects was 65 years (range: 19 to 81) and most subjects (67.1%) 
were male. At baseline, most subjects had an ECOG score of 0 (28.0%) or 1 (62.2%). Eight (9.8%) 
subjects had a baseline ECOG score of 2. Of those with AML, all subjects had previously been 
treated for AML; most had received 1 or 2 prior therapies (25.6% and 23.2% of subjects, 
respectively). Forty-eight (58.5%) subjects had 1 previous complete remission or partial remission 
with prior treatment, 59 (72.0%) were refractory to their last therapy, and 33 (40.2%) have 
experienced only treatment failure. Of the subjects with AML, the median time from initial AML 
diagnosis to the date of first dose was 0.89 years (0.0-11.6 years). Twenty-seven (32.9%) subjects 
had secondary AML, and 25 (30.5%) subjects had AML secondary to prior MDS.
In Part A, responses occurred at exposures achieved with a dose of CC-90009 ≥ 3 mg on schedules 
with 5 or more consecutive dosing days. Objective responses were seen in subjects treated at doses 
of 3.0 and 3.6 mg. One (33.3%) subject in Dose Level 5 (3.6 mg on Days 1 to 5) had a response 
of MLFS, 1 (6.7%) subject in Dose Level 6 (3.0 mg on Days 1 to 5) had a response of CRi, 
2 (25.0%) subjects in Dose Level 9 (3.6 mg with dexamethasone premedication on Days 1 to 5) 
had a response (CR in 1 subject and CRi in the second subject), 4 (57.1%) subjects in Dose Level 
11 (3.6 mg on Days 1 to 7) had a response (CR in 2 subjects and MLFS in 2 subjects), and 3 
(33.3%) subjects in Dose Level 12 (3.0 mg on Days 1 to 10) had a response (CRi in 2 subjects and 
MLFS in 1 subject). In Part B at 3.6 mg with dexamethasone premedication on Days 1 to 5, 2 
(25.0%) subjects in the R/R AML cohort had a response (CRi in 1 subject and MLFS in the second 
subject). 
All 82 (100.0%) subjects had at least 1 treatment-emergent adverse event (TEAE) and 77 (93.9%) 
subjects had at least 1 TEAE suspected by the investigator to be related to CC-90009. Seventy-
three (89.0%) subjects had at least 1 Grade 3/4 TEAE, 70 (85.4%) subjects had at least 1 treatment-
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emergent serious adverse event (TESAE), 31 (37.8%) subjects had at least 1 TEAE leading to CC-
90009 dose interruption, 3 (4.2%) subjects had at least 1 TEAE leading to CC-90009 dose 
reduction, 7 (8.5%) subjects had at least 1 TEAE leading to the permanent discontinuation of CC-
90009, and 27 (32.9%) subjects had at least 1 TEAE leading to death.
The TEAEs occurring in ≥ 20% of subjects overall were hypocalcemia (64 subjects; 78.0%), 
nausea (49 subjects; 59.8%), diarrhea (49 subjects, 59.8%), hypotension (46 subjects; 56.1%), 
vomiting (31 subjects; 37.8%), hypokalemia (29 subjects; 35.4%), febrile neutropenia (23 subjects; 
28.0%), hypomagnesemia (24 subjects; 29.3%), fatigue (21 subjects; 25.6%), ALT increased and 
AST increased (19 subjects each; 23.2%), hypophosphatemia (21 subjects; 25.6%), acute kidney 
injury (17 subjects, 20.7%), and decreased appetite (19 subjects; 23.2%).
Seventy-seven (93.9%) subjects had at least 1 TEAE suspected by the investigator to be related to 
CC-90009. Treatment-emergent AEs suspected by the investigator to be related to CC-90009 that 
occurred in ≥ 10% of subjects overall were hypocalcemia (60 subjects; 73.2%); hypotension (38 
subjects; 46.3%); nausea (36 subjects; 43.9%); diarrhea (30 subjects; 36.6%); vomiting (23 
subjects; 28.0%); ALT increased (15 subjects; 18.3%); AST increased, fatigue, decreased appetite, 
and hypokalemia (14 subjects; 17.1% each); hyperphosphatemia (13 subjects, 15.9%); 
hypomagnesemia (11 subjects, 13.4%); dizziness, hypophosphatemia, and blood creatinine 
increased (10 subjects, 12.2% each); and acute kidney injury (9 subjects; 11.0%).
Overall, 27 (32.9%) subjects had at least 1 TEAE leading to death. These included acute myeloid 
leukemia in 7 (8.5%) subjects, sepsis in 6 (7.3%) subjects, and pneumonia and septic shock in 2 
(2.4%) subjects each. All other TEAEs leading to death occurred in 1 subject each: bacterial sepsis, 
cardiac arrest, general physical health deterioration, hyperglycemic hyperosmolar nonketotic 
syndrome, Klebsiella sepsis, multiple organ dysfunction syndrome, pneumonia pseudomonal, 
pulseless electrical activity, sepsis syndrome and Stenotrophomonas sepsis. Eight (9.8%) subjects 
had at least 1 TEAE leading to death that was suspected to be related to CC-90009. This included 
sepsis in 3 (3.7%) subjects each. All other TEAEs leading to death occurred in 1 subject each 
(1.2%): bacterial sepsis; Klebsiella sepsis, pneumonia, sepsis syndrome, and Stenotrophomonas 
sepsis.
The categorical term of sepsis includes AE preferred terms of bacterial sepsis, Escherichia sepsis, 
Klebsiella 
sepsis, 
neutropenic 
sepsis, 
sepsis, 
sepsis 
syndrome, 
septic 
shock, 
and 
Stenotrophomonas sepsis. Twenty-four (29%) subjects experienced sepsis in this study: 18 (25%) 
subjects were in Part A and 6 (75%) subjects were in Part B in the R/R AML cohort. No sepsis 
was reported in the 2 subjects enrolled in the R/R HR-MDS cohort in Part B. The rate of sepsis in 
the Part B R/R AML cohort (75%, 6 of 8 subjects) was higher than the overall rate (25%, 18 of 72 
subjects) of sepsis from Part A Dose Escalation of this study, and it was higher than the rate (18%, 
2 of 11 subjects) of sepsis among subjects receiving the same dose of CC-90009 on the same 
schedule in Part A. In Part A, the incidence of sepsis is 15%, 29% and 36% among subjects 
receiving consecutive daily CC-90009 doses of 2.4 mg and below (n = 13), 3.0 mg (n = 24), and 
3.6 mg and above (n = 25), respectively, demonstrating a potential dose-dependent relationship 
between CC-90009 and the development of sepsis. There was no sepsis reported in cohorts with 
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CC-90009 dosed at shorter step intervals (ie, when CC-90009 is dosed on cycle Days 1-3 followed 
by Days 8-10), and this schedule is not being pursued based on a lack of objective responses.
An exploratory analysis of CC-90009 plasma exposures in subjects who developed sepsis showed 
that exposures were elevated by approximately 1.56-fold compared to subjects who did not 
develop sepsis. Additionally, subjects who received strong inhibitors of CYP3A4 enzyme (N=20) 
showed that exposures were elevated by approximately 1.8-fold (median dose-normalized 
AUC24 = 192 ng.hr/mL) compared to subjects who did not receive strong CYP3A4 inhibitors or 
received moderate CYP3A4 inhibitors (N = 59, median AUC24 = 106 ng.hr/mL), suggesting a 
potential drug-drug interaction of CC-90009 with strong inhibitors of CYP3A4.
Comprehensive analysis of available PK, PD, efficacy, safety, and tolerability data led to the 
development of a strategy to reduce the risk of sepsis. The strategy includes evaluating doses of 
CC-90009 lower than 3.6 mg and schedules longer than 5 days that had been selected as the dose 
level for the Part B Dose Expansion. New Part B R/R AML and R/R HR-MDS cohorts will be 
enrolled at CC-90009 dose levels of 2.4 mg Days 1-7 and 3.0 mg Days 1-7. The strategy also 
includes dose reduction of CC-90009 for subjects receiving concomitant strong CYP3A4 
inhibitors.
Please refer to the CC-90009 IB for additional PK summary parameters by individual dose levels
and for more detailed information concerning the available pharmacology, toxicology, drug 
metabolism, clinical studies, and AE profile of CC-90009.
1.2.4
Safety Monitoring Plan
Experience with CC-90009 in humans is limited to two ongoing studies, CC-90009-AML-001 (a 
first-in-human study of CC-90009 monotherapy in subjects with R/R AML or R/R HR-MDS) and
CC-90009-AML-002 (a Phase 1b study of CC-90009 in combination with anti-leukemia agents in 
subjects with AML), and the most extensive clinical information comes from the CC-90009-AML-
001. Therefore, the efficacy and safety profiles of CC-90009 in humans are not yet fully
established. Potential toxicities for CC-90009 are being identified based on data from the two 
ongoing clinical studies, nonclinical studies, and literature review for other CBRN binding agents.
As discussed in Section 1.2.2, clinical pathology findings in cynomolgus monkey studies have 
included decreased body weights, alterations in serum chemistry parameters, and decreases in 
peripheral blood lymphocytes, neutrophils, platelets, and reticulocytes. Histopathologic findings 
included variable changes in lymphoid organs and decreases in bone marrow cellularity.  
Subjects will be monitored for possible toxicity through standard and specialized laboratory tests 
including complete blood counts (CBC), prothrombin time (PT)/partial thromboplastin time 
(PTT)/international normalized ratio (INR), and serum chemistries. Prophylaxis is allowed for 
potential secondary infections due to immunosuppression.
Alterations in serum chemistry parameters in the cynomolgus monkey studies included decreased 
protein, albumin, and calcium. Monitoring in the clinic will include standard serum chemistry 
panels and calcium metabolism monitoring (serum calcium, albumin, magnesium [Mg], 
phosphorous, parathyroid hormone [PTH], total procollagen type 1 N-terminal propeptide [P1NP], 
β-C-terminal telopeptide [β-CTx], and urine calcium/creatinine ratio). Subjects will be admitted 
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as inpatients in Cycle 1 and will either be admitted as inpatients or treated in a Limited Stay Unit 
(LSU) throughout the administration of CC-90009 in Cycle ≥ 2. Additionally, subjects who have 
grade ≥ 2 hypocalcemia during any cycle should be admitted as inpatients throughout 
administration of CC-90009 in subsequent cycles and be monitored as in Cycle 1 (an exception 
can be made for subjects with grade 2 hypocalcemia lasting less than 24 hours that recovers without 
IV calcium [eg, calcium gluconate or calcium chloride] after discussion with the Celgene medical 
monitor). Subjects who dose escalate will be admitted as inpatients in the first cycle of the higher 
dose. Calcium, calcitriol, and vitamin D supplements will be taken starting at least 3 days prior to 
Day 1 of each cycle and continuing until ≥ 3 days after the last dose of CC-90009 in each cycle 
(eg, ≥Day 8 when CC-90009 is administered on Days 1 to 5). Guidelines for the management of 
hypocalcemia are provided in Section 7.2.13.2.
Standard eligibility criteria are included to ensure acceptable baseline organ function and lack of 
clinically significant comorbid disease (refer to Sections 4.2 and 4.3).
Subjects are at risk for tumor lysis syndrome (TLS). Eligibility criteria require normal renal 
function and baseline serum chemistries (uric acid, potassium, lactate dehydrogenase [LDH])
consistent with a lower risk of TLS.  Subjects will be closely monitored for laboratory changes 
suspicious for TLS on Days 1 through 5 in Cycle 1.  Hospitalization for management of suspected 
TLS with hypouricemic agents, IV hydration, and correction of electrolyte abnormalities is 
recommended (refer to Section 7.2.13.1 and Appendix I). 
Infusions of a chemotherapeutic agent may cause infusion reactions ranging from localized 
injection site reactions to severe and life-threatening infusion reactions.  Subjects should be 
monitored closely during the administration of CC-90009 and for at least one hour after 
completion.  Guidelines for management of infusion reactions are provided in Section 7.2.13.7.
Although CC-90009 modulates cereblon, the same molecular target of the
IMiD™
immunomodulatory drugs (thalidomide and its analogues, eg, lenalidomide, pomalidomide), 
CC-90009 is mechanistically different. Interaction of CC-90009 with cereblon does not lead to 
degradation of the same set of proteins as the IMiD™immunomodulatory drugs. Reproductive 
studies have not been conducted with CC-90009.  Subjects will be required to follow the CC-90009 
Pregnancy Prevention Plan (PPP) for Celgene Clinical Trials as described in Section 6.1.1 and
Appendix L.
Subjects given CC-90009 at daily doses ≥ 3.6 mg will be administered concurrent dexamethasone 
per Section 7.2. Subjects enrolled on other dose levels may be administered corticosteroid 
premedication as per SRC recommendation (eg, at the 3.0 mg dose level on the Days 1-7 and Days 
1-10 schedules).
Subjects may be at risk for hypotension, infections (eg, sepsis), and other potential hematological 
and non-hematological toxicities. Subjects will be closely monitored for possible toxicity 
throughout the study by physical exam, vital sign and AE collection, through standard and 
specialized laboratory tests including hematology and serum chemistry labs and electrocardiogram 
(ECG). Refer to Section 7.2.13.4 for guidelines on infection prophylaxis, Section 7.2.13.8 for 
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guidelines on management and grading of hypotension, and Table 4 through Table 7 (D1-5 
schedule), Table 31 through Table 38 (D1-3/8-10, D1-7, and D1-10 schedules).
Exploratory analyses of CC-90009 plasma exposures indicated a potential drug-drug interaction 
of CC-90009 with strong inhibitors of CYP3A4. Please refer to Section 7.2.15 for guidelines on 
dose modifications of CC-90009 for concomitant use of strong CYP3A4 inhibitors.  
The global coronavirus disease 2019 (COVID-19) pandemic has been identified as a potential risk 
to clinical trial subjects in general. Immunocompromised patient populations such as those with 
R/R AML and HR-MDS may be more susceptible to infections, including SARS-CoV-2 (severe 
acute respiratory syndrome coronavirus 2) infections. In addition, the potential impact of CC-
90009 administration on the frequency or severity of SARS-CoV-2 infections in subjects with R/R 
AML or HR-MDS are currently unknown. To mitigate this potential risk, RT-PCR testing for 
SARS-CoV-2 infection will be mandatory for all subjects. Subjects with recent or acute SARS-
CoV-2 infections will be excluded (Section 4.3) or delay start of treatment as defined in 
Section 6.1. If a subject has a confirmed SARS-CoV-2 infection while on study treatment, dose 
delay or interruption of study treatment is required as described in Section 7.2.13.4.1. An 
exploratory analysis of the impact of SARS-CoV-2 serologic status on subjects receiving 
CC-90009 may be performed.
The study has been designed with study visits that allow for close monitoring of subjects’ safety 
throughout the clinical trial (Section 6), and subjects are encouraged to contact the investigator if 
an intercurrent illness develops between study visits. Testing for COVID-19 to inform decisions 
about clinical care during the study should follow local standard practice. Non-live COVID-19 
vaccination is considered a simple concomitant medication within the study. However, the efficacy 
and safety of non-live vaccines (including non-live COVID-19 vaccines) in subjects receiving CC-
90009 is unknown.
Based on the current knowledge of the safety profile of CC-90009 available from non-clinical and 
clinical studies, and considering the safety monitoring and management, dosing, precautions, and 
guidance specified in the CC-90009-AML-001 protocol and the Investigator’s Brochure, the 
benefit-risk balance is assessed as acceptable for continuing with the current clinical study in AML 
and HR-MDS subjects with limited treatment options.
1.3
Rationale
1.3.1
Study Rationale and Purpose
CC-90009 is a new IP that has a strong biological rationale for the treatment of subjects with AML
and HR-MDS (refer to Section 1.2). This Phase I study is designed to determine the safety and 
tolerability of CC-90009 as well as evaluating the biologic and clinical activity in subjects with
R/R AML or R/R HR-MDS.  The study will be conducted in two parts: dose escalation (Part A) 
and dose expansion (Part B). 
1.3.2
Rationale for the Study Design
In Part A, a modified accelerated titration design (Simon, 1997) will be used to establish initial
safety and tolerability and identify tolerable dosing schedules for expansion in Part B. The 
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modified accelerated titration design allows for fewer subjects to be treated at a lower CC-90009 
dose that is potentially not efficacious. Escalations will be decreased from 100% to ≤ 50% when 
≥ 2 subjects experience a CC-90009-related Grade ≥2 adverse event in the dose-limiting toxicity 
(DLT) window (may be different cohorts), or ≥1 subject experiences a DLT within the DLT 
window. At that time the current cohort and all subsequent cohorts will be expanded enrolling 3 
to 6 subjects using a traditional 3+3 design (Storer, 1989). Refer to Figure 2 for sample dose 
escalation schemes and Section 7.2 for additional dose escalation information. 
One or more dosing regimens may be selected for cohort expansion in Part B to obtain additional 
safety and efficacy information for larger cohorts of subjects (up to approximately 20 in each arm).
At least one cohort will include R/R AML subjects, including subjects who relapse after allogeneic 
HSCT, who are in second or later relapse, who are refractory to initial induction or re-induction 
treatment, who are refractory to or relapsed after hypomethylating agents (HMA failure defined as 
primary progression or lack of clinical benefit after a minimum of 6 cycles or unable to tolerate 
HMA due to toxicity), or who relapse within 1 year of initial treatment (excluding those with 
favorable-risk status) and at least one cohort of relapsed or refractory HR-MDS subjects will be 
enrolled in Part B at the dose/schedule selected by the SRC based on available data from Part A.
1.3.3
Rationale for Dose, Schedule, and Regimen Selection
Based on the findings in the pivotal repeat-dose toxicity studies, the cynomolgus monkey is the 
more sensitive species for CC-90009-mediated toxicities, and therefore, should be used for 
estimating a starting dose in the initial clinical study with CC-90009. In the definitive 28-day 
repeat-dose toxicity study in monkeys, daily treatment at 0.03 mg/kg was identified as the HNSTD. 
The highest dose of 0.3 mg/kg/day administered for a total of 10 days (Days 1 to 5 and Days 15 to 
19) was considered to be severely toxic based on adverse clinical condition and bone marrow 
toxicity. The adverse clinical condition was determined in a subsequent study to be related to the 
hypocalcemic effect at this dose, could be alleviated by calcium and vitamin D supplementation, 
and was rapidly reversible following discontinuation of CC-90009. The hypocalcemic effect is 
monitorable in humans and calcium, calcitriol, and vitamin D supplementation will be employed 
in this study prior to and concomitant with study drug dosing.  
At the mid-dose of 0.1 mg/kg/day, the hypocalcemic effect was slight (-11 to -17%) after 4 weeks 
of daily dosing and was not considered adverse. Although marked bone marrow hypocellularity 
was observed at the end of the 28-day dosing period and was considered as severely toxic, the 
same dose of 0.1 mg/kg/day given daily on Days 1 to 7 and Days 12 to 22 in the 28-day exploratory 
toxicology study only resulted in a slight decrease in bone marrow cellularity. Therefore, when 
given intermittently for 7 days every two weeks, this dose was not severely toxic. Further 
supporting intermittent dosing, the highest dose of 0.3 mg/kg/day administered daily for 5 days 
every 2 weeks resulted in slight to moderate hypocellularity that recovered within 28 days in all 
but one animal. The recovery at this dose level was likely delayed by the second 5-day dosing 
period on Days 15 to 19. Although this dose was severely toxic based on the bone marrow findings, 
bone marrow hypocellularity is common in standard of care AML therapy, such as 7+3 induction 
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chemotherapy, and is an acceptable toxicity in this population as long as hematopoietic recovery
is observed following treatment discontinuation.
Based on the monkey study observations, the initial schedule to be evaluated for CC-90009 is once 
daily (QD) dosing on Days 1 to 5 of 28 day cycles for up to 4 cycles. This schedule is designed to 
allow short intensive cytotoxic therapy followed by a bone marrow recovery period and is 
consistent with standard induction therapy paradigms in AML. Initial dosing only on Days 1 to 5 
mitigates the risk of delayed bone marrow recovery observed with the second 5-day dosing period 
(Days 15 to 19) at 0.3 mg/kg in monkeys. This initial schedule is also selected to mitigate 
hypocalcemia as the effect became adverse when the 0.3 mg/kg animals were dosed for longer 
than 5 days. The initial schedule of CC-90009 given on Days 1 to 5 supports an initial human 
starting dose of 0.3 mg, which provides an approximately 20-fold margin below the severely toxic 
dose (STD) of 0.3 mg/kg given on Days 1 to 5 and Days 15 to 19 in the 28-day monkey study. 
The starting doses calculated based on doses tested in the 28-day monkey studies and the ICH S9 
recommended 6-fold margin in oncology patients are given in Table 1. Overall, CC-90009 exhibits 
an acceptable safety profile in preclinical species for an oncology clinical candidate, and the 
toxicology program for CC-90009 adequately supports the conduct of clinical trials in oncology 
patients.
After review of the data from the first 5 dose levels, an additional schedule of CC-90009 
administered once daily on Days 1-3 and Days 8-10 of each 28 day schedule (D1-3/D8-10) may 
be explored. The rationale for this schedule is based on the clinical experience to date using once 
daily dosing on Days 1 to 5 of 28 day cycles. Study drug-related non-hematologic toxicities were 
mostly observed during the later dosing days (Days 3-5) and were rapidly reversed once dosing 
ended. Shorter intervals of dosing (ie, 3 days) could mitigate non-hematologic toxicity.  
Meanwhile, the observed blast reduction with Days 1-5 dosing persisted through Day 8, but, in 
several patients, blasts recovered between Days 15- 28. Therefore, repeat dosing for 3 days on 
Days 8-10 could allow further blast reduction while still allowing a study drug-free interval of > 2 
weeks for recovery from bone marrow myelosuppression. Finally, if rapid death of leukemic blasts 
is associated with non-hematologic toxicity (eg, tumor lysis syndrome or cytokine mediated 
inflammatory response/hypotension), the Days 1-3 and Days 8-10 schedule could mitigate this 
toxicity by triggering a slower initial blast reduction either via the shorter interval of dosing or 
through the use of a lower dose on Days 1-3 (see example in Figure 3).
After review of the clinical data where CC-90009 has been evaluated in consecutive daily dosing 
on the Days 1-5 (D1-5) and intermittent (D1-3/8-10) schedules, extended consecutive days of 
dosing may be explored (eg, Days 1-7 and/or Days 1-10). The rationale for increasing the days of 
dosing to either Days 1-7 or Days 1-10 schedules stems from review of the kinetics of peripheral 
blast decrease and timing of rebound as well as PD findings (eg, GSPT1 decrease and recovery).
On 07 June 2019, the SRC recommended extending the number of dosing days to Days 1-7 as a 
future cohort in dose escalation. This was partly based on the observation that in some patients 
with high peripheral blood leukemic blasts, the Days 1-5 dosing was suboptimal. In these subjects, 
the blasts were still dropping but had not reached nadir by the last consecutive daily dose on Day 
5. Therefore, extending the dosing days at a dose level that was tolerated on the Days 1-5 schedule 
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would have potential to further deepen the leukemic blast reduction. Study drug-related non-
hematologic toxicities (eg, tumor lysis syndrome or cytokine mediated inflammatory 
response/hypotension) have been
manageable with the implementation of concurrent
dexamethasone for CC-90009 dosing for the current 3.6 mg dose levels. Decision to test the 
extended consecutive days of dosing (ie, Days 1-7 and Days 1-10 schedules) will be based on SRC 
review of toxicity, PK profiles, and PD findings from the Days 1-5 and Days 1-3/8-10 dosing 
schedules.
Table 1:
Starting Doses in Humans Based on the Doses Tested in the 28-day 
Monkey Studies with CC-90009
Monkey Dose and 
Schedule
(mg/kg/day)
HED
(mg/kg)a
HED
(mg/day)b
Safety 
Factorc
HED/Safety 
Factor
(mg/day)
Human 
Starting 
Dose 
(mg/day)d
Predicted Exposure 
Multiple Based on 
Monkey Dose
(AUC, C5min)e
0.03 QD for 
28 days (HNSTD)
0.0097
0.6
6
0.1
0.1
6x, 15x
0.1 x 7 days Q2W 
for 28 days
(HNSTD)
0.032
1.92
6
0.3
0.3
11x, 15x
0.3 x 5 days Q2W 
for 28 days (STD)
0.097
5.8
6
1
1
7x, 15x
Abbreviations:  AUC = area under the concentration-time curve; C5min = plasma concentration of the drug at 5 minutes 
postdose; HED = human equivalent dose; HNSTD = highest non-severely toxic dose; Q2W = every 2 weeks; QD = 
every day; STD = severely toxic dose.
a Value calculated using HED conversion factor from the July 2005 FDA Guidance for Industry: “Estimating the 
Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers” (FDA, 2005).
b Value calculated for a 60-kg human.
c Value from ICH S9 Guideline: “Nonclinical Evaluation for Anticancer Pharmaceuticals” (ICH, 2009).
d Using the allometry-derived plasma clearance (18.9 L/hr) and volume of distribution (1.44 L/kg) estimates, the 
predicted steady state C5 min and systemic exposure (AUC24hr) of CC-90009 following daily administration of a 
0.3 mg IV infusion dose in a 60-kg human are 3.4 ng/mL and 15.7 ng·hr/mL, respectively.  
e Predicted exposure multiple equals animal value divided by predicted human value at each corresponding human 
starting dose.
Refer to the Investigator’s Brochure for detailed information. 
1.3.4
Rationale for Dose and Dosing Schedule in Part B Dose Expansion
Data generated from Part A Dose Escalation of the study suggest a manageable safety profile and 
encouraging preliminary clinical activity of CC-90009 in subjects with R/R AML (Section 1.2.3).
At the completion of Part A Dose Escalation, a total of 72 subjects were treated with CC-90009. 
Preliminary safety and efficacy data are available for these 72 subjects treated in Part A. All data 
were assessed both internally and by SRC, and a non-tolerated dose (NTD) was successfully 
determined on 3 of the 4 schedules evaluated. The Days 1-3/8-10 schedule was not pursued further 
due to lack of efficacy prior to declaring either a maximum tolerated dose (MTD) or NTD. Based 
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on the observed DLTs and definitions of NTD and MTD set in the protocol, the SRC declared 3.0 
mg Days 1-5 without dexamethasone premedication and 3.6 mg Days 1-5 with dexamethasone 
premedication as MTDs on the Days 1-5 schedule. After further review of preliminary safety, anti-
leukemic activity and PK/PD data from all dose levels, the SRC recommended 3.6 mg Days 1-5 
with dexamethasone premedication as the dose and schedule to be expanded for the initial cohorts 
of R/R AML and R/R HR-MDS subjects in Part B.
Overall, evidence of anti-leukemic activity (decreases in bone marrow and/or peripheral blasts) 
was seen in subjects treated with CC-90009 at 1.2 mg and above with a trend to deeper and more 
sustained reductions at the highest dose levels. Objective responses were observed in cohorts with 
5 or more days of continuous dosing at 3.0 and 3.6 mg with a trend for better efficacy at 3.6 mg. 
A higher dose of 4.5 mg on this schedule was not tolerated.
Attempts to shorten the dosing schedules with intermittent dosing of either 3.0 mg or 3.6 mg on 
Days 1-3 and 8-10 were unsuccessful due to lack of efficacy. While these regimens were tolerated, 
they were not pursued based on lack of objective response: this intermittent dosing schedule did 
not sufficiently suppress leukemic blasts, which increased in the peripheral blood on non-dosing 
days.
Dosing schedules with more than 5 consecutive days (3.6 mg Days 1-7 and 3.0 mg Days 1-10) 
were not well tolerated at dose levels tested based on DLTs using the current hypotension grading 
in Protocol Amendment 7 (Table 12), interruptions and missed doses. However, responses were 
noted in both of these dose levels.
In Part A, at the selected Part B dose and schedule of 3.6 mg Days 1-5 with dexamethasone 
premedication, all subjects received 100% of the planned dose when given dexamethasone 
premedication and no subject experienced dose-limiting hypotension. Two (25%) subjects 
achieved objective responses (CR and CRi).
Selection of 3.6 mg as compared to 3.0 mg on the Days 1-5 schedule was further supported by PK 
and PD data. PK of CC-90009 was evaluated after single- and repeat-dose administration during 
the first dosing cycle. Preliminary results have demonstrated dose-dependent exposure increases 
in CC-90009 across the dose range of 0.6 mg to 4.5 mg. The PK profile is generally consistent 
across doses and dosing schedules. Preliminary analysis of exposure-efficacy and exposure-safety 
correlations from Part A data suggest that lower daily exposure (as measured by AUC24) achieved 
by 3.6 mg relative to 4.5 mg would be anticipated to mitigate risk of higher-grade hypotension, 
while 3.6 mg relative to 3.0 mg would be anticipated to lead to greater likelihood of achieving 
systemic exposures that are considered sufficient for clinical response in a greater proportion of 
subjects.
PD biomarkers for GSPT1 and downstream pathway markers were assessed in evaluable subjects.
A dose-dependent decrease in GSPT1 levels in peripheral blood blasts and T cells was observed, 
with a maximal >90% decrease observed for higher dose levels. At the selected Part B dose of 3.6 
mg, the degradation of GSPT1 achieved the desired threshold within 24 hrs in most subjects and 
was maintained at this level throughout the dosing period.
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In light of dose-related pharmacokinetics, evidence of deep GSPT1 degradation and on-target 
activity, promising anti-leukemic activity, and acceptable safety and benefit-risk balance, the SRC 
recommended proceeding to Part B Dose Expansion at the MTD of 3.6 mg with dexamethasone 
premedication on Days 1-5 in patients with R/R AML and R/R HR-MDS.
After an initial 8 R/R AML subjects enrolled in Part B at dose level 3.6 mg Days 1-5 with 
dexamethasone premedication, a high rate of sepsis (75%) was observed in this cohort, and 
enrollment to both R/R AML and R/R HR-MDS cohorts were paused. There were no significant 
findings on demographic and baseline characteristics of R/R AML subjects enrolled at the same 
dose level (CC-90009 3.6 mg D1-5 with or without dexamethasone premedication) in Part A Dose 
Escalation (n = 11) and Part B Dose Expansion (n = 8). In both Parts A and B, preliminary analyses 
of pharmacokinetic data demonstrated increased CC-90009 exposure (1.56-fold) among subjects 
who developed sepsis as well as increased exposure (1.8-fold) among subjects who received 
concomitant strong CYP3A4 inhibitors. Preliminary modeling of exposure-sepsis and exposure-
clinical response relationships indicated that cumulative exposure of CC-90009 (AUCCUM) was 
less predictive of sepsis than daily exposure (odds ratio [95% confidence interval]: 2.55 [1.17–
6.65] for AUCCUM as the predictor vs. 3.84 [1.35–13.35] for AUC24 as the predictor) and that 
AUCCUM was more predictive of clinical response than AUC24 (odds ratio [95% Confidence 
Interval]: 5.06 [1.61–21.16] for AUCCUM vs. 3.04 [0.97–13.07] for AUC24). Comprehensive
analysis of available PK, PD, efficacy, safety, and tolerability data led to the development of a
strategy to reduce the risk of sepsis. The strategy includes evaluating doses of CC-90009 lower 
than 3.6 mg and schedules longer than 5 days that had been selected as the dose level for the Part 
B Dose Expansion. New cohorts in Part B will be enrolled at CC-90009 dose levels of 2.4 mg 
Days 1-7 and 3.0 mg Days 1-7. R/R AML and R/R HR-MDS subjects will be pooled in each cohort 
with 6 to 40 subjects enrolled in each cohort, including up to 20 subjects with R/R AML and up to 
20 subjects with R/R HR-MDS in each cohort. The strategy also includes dose reduction of CC-
90009 for subjects receiving concomitant strong CYP3A4 inhibitors. The new Part B cohorts will 
enroll subjects in parallel. Up to 6 subjects per cohort will be initially enrolled as a safety run-in. 
The SRC will assess tolerability of the dose and schedule for these initial subjects that completed
at least one cycle of study treatment based on the Part A stopping criteria (Section 7.2.8) and 
recommend further expansion of one or more cohorts. The expanded cohort(s) will be monitored 
for the excess toxicities including sepsis utilizing the non-binding Bayesian stopping criterion on 
a continuous basis (Section 9.9.3). Subjects of R/R AML and R/R HR-MDS enrolled in the 
expansion cohorts will be pooled for analysis of safety, PK, and PD. The SRC will continue to 
review safety and preliminary efficacy data regularly throughout the study and make 
recommendations about study continuation, cohort continuation, and dose modification, as 
appropriate.
1.3.5
Rationale for Pharmacodynamics and Potential Predictive Biomarkers 
The therapeutic hypothesis for CC-90009 activity in AML and MDS is that CBRN-dependent 
substrate degradation and induction of UPR preferentially kill leukemic cells, and a therapeutic 
index of 2- to 5-fold over normal hematopoietic stem cells can be achieved with intermittent 
dosing. CC-90009 binding to the CRL4CRBN complex promotes ubiquitination and degradation of 
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substrates. Substrate degradation by CC-90009 leads to activation of the UPR pathway and induces 
apoptosis in AML cells.
CC-90009 is broadly active at killing leukemic cells in ex-vivo cultures of primary bone marrow 
cells from AML patients, while a spectrum of sensitivities have been observed across a 20 cell line 
AML panel. In vitro studies in AML cell lines show that the extent of CRBN-dependent substrate
reduction by CC-90009 is predictive of apoptosis sensitivity.
Blood will be collected predose and postdose for the purpose of measuring PD markers of 
CC-90009 activity. Priority PD endpoints include quantification of CBRN substrates and 
quantification of markers of UPR and nonsense-mediated decay (NMD). A portion of bone 
marrow tissue (biopsy and aspirate), collected before and during treatment, will also be utilized 
for evaluation of PD endpoints.
Ongoing studies are evaluating the exposure-response relationships to PD and efficacy 
endpoints to model the dose and exposure profile predicted to affect biologic and clinical activity 
with CC-90009 therapy. This modeling along with PD data collected will be used to support 
decisions about dose and schedule during the study. In the expansion phase of the study, the 
relationship between PD markers and safety and/or efficacy will be further explored in both AML 
and HR-MDS cohorts.
No patient selection hypotheses have been developed for prospective clinical testing at this time. 
Correlative analyses of molecular characteristics of AML cell lines with differential sensitivities 
to CC-90009 are ongoing to generate such hypotheses. Further, expanded evaluations of ex vivo 
treated primary AML bone marrow samples, with molecular characterization, have been initiated. 
For the purpose of retrospective evaluation of potential predictive markers of CC-90009 efficacy, 
bone marrow and/or blood samples may be characterized in molecular and cellular assays,
potentially including, but not limited, to cytogenetics, gene variants analyses (eg, gene 
sequencing), messenger ribonucleic acid (mRNA)/microRNA expression (eg, RNA sequencing), 
functional assays (eg, engraftment potential), clonal architecture, ex vivo sensitivity assays with 
CC-90009, and immunophenotyping.
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Celgene Corporation
CC-90009-AML-001 Amendment 9
Final: 31 Mar 2022
45
2
STUDY OBJECTIVES AND ENDPOINTS
Table 2:
Study Objectives
Primary Objectives
The primary objectives of the study are:

To determine the safety and tolerability of CC-90009. 

To define the non-tolerated dose (NTD), the maximum tolerated dose (MTD) and/or the recommended 
Phase 2 dose (RP2D) of CC-90009.  
Secondary Objectives
The secondary objectives are:

To provide information on the preliminary efficacy of CC-90009 in R/R AML and R/R HR-MDS.  

To characterize the PK of CC-90009 in plasma and urine. 
Exploratory Objectives
The exploratory objectives are:

To explore the relationship between systemic exposure of CC-90009 and measures of toxicities, 
effectiveness, and PD biomarkers.

To evaluate molecular and/or cellular markers in the bone marrow and blood that may be predictive of 
efficacy with CC-90009.

To characterize the PK of hydroxypropyl-beta cyclodextrin in plasma and urine.

To assess the impact of SARS-CoV-2 serologic status on subjects with R/R AML or HR-MDS receiving 
CC-90009.
Data from exploratory objectives may not be included in the Clinical Study Report.
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Celgene Corporation
CC-90009-AML-001 Amendment 9
Final: 31 Mar 2022
46
Table 3:
Study Endpoints
Endpoint
Name
Description
Timeframe
Primary 
Safety 
endpoints
DLTs, NTD, and MTD evaluated using the 
NCI CTCAE criteria, Version 4.03. Adverse events, 
including treatment-emergent adverse events (TEAEs), 
laboratory assessments, vital signs, ECG results, ECOG 
performance status, LVEF assessments, physical 
examinations, and vital signs.
Screening until 
28 days after the last 
dose of CC 90009 for 
each subject during 
both dose escalation 
and expansion phases.
Secondary
Preliminary 
efficacy
Determined by response rates of AML by disease 
response criteria.
Dose escalation and 
dose expansion; 
throughout Treatment 
Period and the 
Follow-up Period 
(refer to Sections 6.3.2
and 6.3.3)
Overall survival, relapse-free survival, progression-free 
survival, event-free survival, duration of remission, 
duration of response, and time to remission/response for 
AML subjects.
Determined by response rates of HR-MDS by disease 
response criteria.
Dose escalation and 
dose expansion; 
throughout Treatment 
Period and the 
Follow-up Period 
(refer to Sections 6.3.2
and 6.3.3) of Part B 
only
Overall survival, relapse-free survival, progression-free 
survival, event-free survival, duration of remission, 
duration of response, time to AML transformation, and 
time to remission/response for HR-MDS subjects.
PK 
endpoints
Noncompartmental PK parameters of CC-90009 in 
plasma and urine including observed maximum 
concentration (Cmax), area under the plasma 
concentration time-curve from time 0 to 24 hours 
postdose (AUC24), time to peak (maximum) plasma 
concentration (tmax), terminal half-life (t1/2), total body 
clearance of the drug from the plasma (CL), and volume 
of distribution at steady-state (Vss), % dose excreted in 
urine as unchanged (Fe), and renal clearance (CLR).
Dose escalation and/or
dose expansion, when 
feasible
Exploratory
PD 
endpoints

CRBN substrate protein level

RNA and/or protein levels of markers of 
unfolded protein response and non-sense 
mediated decay (NMD) of RNA 

Blasts in bone marrow and peripheral blood

Leukemic stem cell quantification in bone
marrow
Dose escalation and 
dose expansion; 
throughout Treatment 
Period and the 
Follow-up Period 
(refer to Sections 6.3.2
and 6.3.3)
Predictive/ 
prognostic
endpoints

Standard AML diagnostics (cytogenetics, 
FISH, and molecular [eg, KIT, FLT-3, NPM1, 
CEBPα])

Expanded gene sequence analysis (myeloid 
cancer gene panel)

Gene expression (eg, RNA sequence)

Protein expression of mechanism markers (eg, 
CRBN substrates, CRBN, endoplasmic 
reticulum stress markers)

Minimal residual disease (MRD)
Dose escalation and 
dose expansion; 
throughout Treatment 
Period and the 
Follow-up Period 
(refer to Sections 6.3.2
and 6.3.3)
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Protocol CC-90009-AML-001
Celgene Corporation
CC-90009-AML-001 Amendment 9
Final: 31 Mar 2022
47
Table 3:
Study Endpoints
Endpoint
Name
Description
Timeframe
PK 
endpoints

Clinically relevant covariates of PK parameters

Profile of CC-90009 metabolites in plasma 

Exposure-response relationships

Noncompartmental PK parameters of HPBCD 
in plasma and urine including Cmax, AUC24, tmax, 
t1/2, CL, Vss, Fe, and CLR.
Dose escalation and/or
dose expansion 
SARS-CoV-
2 serologic 
status

Exploratory measurements of SARS-CoV-2 
serology (anti-SARS-CoV-2 total or IgG) from 
serum samples collected at baseline and 
specified timepoints.
Dose expansion
Abbreviations:  AML = acute myeloid leukemia; CEBPα = CCAAT/enhancer binding protein (c/EBP), alpha; CRBN 
= cereblon; DLT = dose-limiting toxicity; ECG = electrocardiogram; ECOG = eastern cooperative oncology group; 
FISH = fluorescence in situ hybridization; FLT-3 = FMS-like tyrosine kinase 3; HPBCD = Hydroxypropyl beta-
cyclodextrin, IgG = immunoglobulin G; KIT = stem cell factor receptor; LVEF = left ventricular ejection fraction; 
MTD = maximum tolerated dose; NCI CTCAE = National Cancer Institute Common Terminology Criteria for 
Adverse Events; NPM1 =
nucleophosmin 1; NTD = non-tolerated dose; PD = pharmacodynamic; 
PK = pharmacokinetic; RNA = ribonucleic acid; SARS-CoV-2 = severe acute respiratory syndrome coronavirus.
3
OVERALL STUDY DESIGN
3.1
Study Design
Study CC-90009-AML-001 is an open-label, Phase 1, dose escalation and expansion, 
first-in-human clinical study of CC-90009 in subjects with relapsed or refractory AML (Appendix 
B) or in subjects with relapsed or refractory higher-risk MDS (Appendix E and Appendix G). The 
dose escalation part (Part A) of the study will evaluate the safety and tolerability of escalating 
doses of CC-90009, administered intravenously, and determine the MTD of CC-90009. In Part A, 
two formulations were tested. The expansion part (Part B) will further evaluate the safety and 
efficacy of CC-90009 administered at or below the MTD in selected expansion cohorts of up to 
approximately 20 evaluable subjects in each disease indication (R/R AML and R/R HR-MDS) in 
order to determine the RP2D. One or more dosing regimens may be selected for cohort expansion 
(at a minimum, one in R/R AML and one in R/R HR-MDS). MDS subjects will only be enrolled 
during Part B. Parts A and B will consist of 3 periods:  Screening, Treatment, and Follow-up. 
Leukemia response will be determined by the Investigator.  Disease assessment will be based on 
the International Working Group (IWG) Response Criteria in AML (Cheson, 2003; refer to 
Appendix C). MDS response will be based on the IWG Response Criteria for Myelodysplasia 
(Cheson, 2006; refer to Appendix F). 
Screening Period
The Screening Period starts 28 days prior to first dose of CC-90009. The informed consent 
document (ICD) must be signed and dated by the subject and the administering staff prior to the 
start of any other study procedures. All screening tests and procedures must be completed within 
the 28 days prior to the first dose of CC-90009.
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CC-90009-AML-001 Amendment 9
Final: 31 Mar 2022
48
Treatment Period
In the Treatment Period, CC-90009 will be administered intravenously QD on Days 1-5 of each 
cycle for up to 4 cycles in the absence of disease progression (as defined in Section 6.4), relapse, 
unacceptable toxicity, or subject/physician decision to withdraw. Modified dosing schedules 
(eg, increasing from 5 consecutive days to up to 7 or 10 consecutive days of dosing or increasing 
infusion length) may be evaluated in additional cohorts, if necessary, based on toxicity, PK 
profiles, and PD findings. An additional schedule of CC-90009 administered once daily on Days 
1-3 and Days 8-10 of each 28 day cycle will be explored. Tables of Events for the alternate dosing 
schedules (eg, D1-3/D8-10, D1-7, and D1-10 Dosing Schedules) are located in Appendix K and 
Appendices M-O. Those who demonstrate benefit from treatment without unacceptable toxicity 
(any complete remission [CR], morphologic leukemia-free state [MLFS], partial remission [PR], 
or stable disease with discussion with Medical Monitor) may continue treatment beyond Cycle 4 
until loss of that benefit, unacceptable toxicity, or subject/physician decision to withdraw.
All subjects will be required to start calcium, calcitriol, and vitamin D supplementation at least 
3 days prior to Day 1 of each cycle and continue until ≥ 3 days after the last dose of CC-90009 in 
each cycle (eg, ≥ Day 8 when CC-90009 is administered on Days 1-5, ≥ Day 10 when CC-90009 
is administered on Days 1-7, or ≥ Day 13 when CC-90009 is administered on Days 1-3/Days 8-10
or Days 1-10).
In Cycle 1 of Part A, a bone marrow evaluation will be performed on Days 28 (± 3 days). Based 
on the Day 28 bone marrow evaluation, subjects with hypoplastic bone marrow, without evidence 
of persistent leukemia, who have Grade ≥ 3 neutropenia will be followed for an additional 2 weeks 
for safety monitoring in Cycle 1 (total duration of 42 days; refer to Figure 1). An additional bone 
marrow assessment will be performed at the time of hematologic recovery or Day 42 (± 3 days).
Thus, in Part A, the window for evaluation of DLT during Cycle 1 will be up to 42 days (28 or 42 
days). In Part B, Cycle 1 will be 28 days in length. Cycles ≥2 will be 28 days in length. Subsequent 
cycles should start ≤ 7 days following the last day of the previous cycle. Permitted treatment delays 
are described in Section 7.2.12. 
Retreatment will be allowed for subjects who transition from the treatment period to the follow-
up period of the study in CR, CRi or Morphologic CR with partial hematologic recovery (CRh)
and who have relapsed after a prolonged remission (eg, > 6 months). The subject cannot have had 
another systemic anti-cancer therapy upon relapse. The subject can be considered for retreatment 
after confirmation that they continue to meet the eligibility criteria for the study and after 
discussion with the Sponsor medical monitor. Subjects who discontinue treatment due to adverse 
event or disease progression are not eligible for retreatment. Subjects will only be considered DLT 
evaluable during the first cycle of their initial enrollment in Part A (Section 7.2.3). The subject 
will not be re-considered in the efficacy evaluation (Section 9.1).
Follow-up Period
In the Follow-up Period, all subjects will be followed for 28 days (± 3 days) after the last dose of 
CC-90009 for safety. 
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Celgene Corporation
CC-90009-AML-001 Amendment 9
Final: 31 Mar 2022
49
Subjects without documented progression of disease (or relapse) will have efficacy evaluations of 
complete blood counts and peripheral blood smears performed every subsequent 8 weeks 
(± 1 week) for the 1st year and every 12 weeks (± 2 weeks) for the 2nd year or until progression of 
disease (or relapse), initiation of a new anticancer therapy, withdrawal of consent from the study, 
death, or the End of Trial, whichever comes first. A bone marrow evaluation will be completed at 
the end of the 1st year and as clinically indicated during the Follow-up Period.
All subjects will be followed for survival follow-up according to the schedule for the efficacy long 
term follow-up for up to 2 years or until death, lost to follow-up, or the End of Trial, whichever 
occurs first. Survival follow-up may be conducted by record review (including public records) 
and/or telephone contact with the subject, family, or the subject’s treating physician.
Part A-Dose Escalation
During the escalation phase (Part A), a modified accelerated titration design (Simon, 1997) will 
be used to establish initial toxicity. Cohorts of one or more subjects each will be administered
CC-90009 at doses that will increase in 100% increments per cohort until ≥ 2 subjects experience 
a CC-90009-related Grade ≥ 2 adverse event (AE) in the DLT window (may be different cohorts), 
or ≥ 1 subject experiences a DLT within the DLT window. At that time the current cohort and all 
subsequent cohorts will be expanded enrolling 3 to 6 subjects. A dose escalation schedule with 
dose increments not to exceed 50% will concurrently be initiated in order to establish the NTD 
and MTD (refer to Section 7.2.2). The initial dose will be 0.3 mg. Sample dose escalation schemes
for Part A are shown in Figure 2. At the study start an initial formulation (Gen 1) was utilized and 
during dose escalation a second formulation (Gen 2b) was introduced to replace Gen 1. The DMA 
residual solvent in the Gen 1 CC-90009 formulation must not exceed the ICH PDE limits in order 
to proceed with dose escalation cohorts above a daily CC-90009 dose of 2.4 mg. Gen 2b CC-90009 
formulation is permitted at daily doses up to 20 mg. The Gen 2b formulation was introduced at the 
fourth dose level (DL4: 2.4 mg QD on Days 1-5) in accordance with study dose escalation schemes 
shown in Figure 2 based on SRC recommendation after review of the data from the initial three 
dose levels using the Gen 1 CC-90009 formulation.
In any cohort of 1, 3 or 6 subjects during dose escalation, all subjects are observed for at least 28 
days and up to 42 days (Cycle 1, DLT window) before the next higher dose cohort can begin
enrollment based on SRC review and recommendation. No more than one subject per day will be 
enrolled in a given dose escalation cohort. Refer to Section 7.2 for detailed information on the dose 
escalation process.
Dose escalation decisions will be made at the discretion of a SRC that will include Investigators 
(and/or designated representatives), the Sponsor’s study physician, safety physician, and the study 
manager. Ad hoc attendees may include the study pharmacokineticist, study statistician, and 
additional study clinical scientists. Other internal and external experts may be consulted by the 
SRC, as necessary.  
The SRC may decide to evaluate a higher dose cohort, additional subjects within a dose cohort, 
intermediate dose cohorts, smaller dose increments, alternate dosing schedules (eg, increasing 
from 5 to up to 10 consecutive days of CC-90009 administration), and/or declare an MTD based 
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Protocol CC-90009-AML-001
Celgene Corporation
CC-90009-AML-001 Amendment 9
Final: 31 Mar 2022
50
on their review of available clinical and laboratory safety data, PK profiles, and PD findings. In 
the event that an alternate dosing schedule is evaluated, the starting dose and schedule will not 
exceed the dose intensity of a dose cohort that has previously met the criteria for dose escalation.
An additional schedule of CC-90009 administered once daily on Days 1-3 and Days 8-10 of each 
28-day schedule may be explored (Figure 3). 
Protocol amendment 5 instated the use of concurrent steroid (dexamethasone or equivalent) to 
mitigate the risk of hypotension in all cohorts with a daily dose of 3.6 mg or higher. The rationale 
for dexamethasone treatment to reduce the risk of hypotension is based on pre-clinical data and 
clinical observations. The NTD of 3.6 mg on Days 1-5 schedule, which was determined based on 
DLT of hypotension, will be reevaluated for tolerability with dexamethasone (or equivalent) 
prophylaxis as a new cohort. Initially 3 subjects will enroll at CC-90009 3.6 mg Days 1-5 with
dexamethasone (see Sections 7.2 and 8.3). If tolerated (eg, 0/3 or 1/6 DLTs), then a new NTD and 
MTD will be established on this schedule with concurrent dexamethasone as described above for 
all cohorts (Section 7, and Sections 7.2.2 – 7.2.5). Protocol amendment 7 extended the 
recommendation for dexamethasone to the 3.0 mg Days 1-10 schedule (see Sections 7.2 and 8.3). 
Part B-Cohort Expansion
Following completion of dose escalation (Part A), one or more dosing regimens may be selected 
for dose expansion with up to approximately 20 evaluable subjects in each disease indication (R/R 
AML and R/R HR-MDS) at a specified dose level. Subjects with HR-MDS will be enrolled only 
during Part B (Figure 4). 
In Part B, subjects with R/R AML who are eligible include subjects who relapsed after allogeneic 
HSCT, who are in second or later relapse, who are refractory to initial induction or re-induction 
treatment, who are refractory to or relapsed after hypomethylating agents (HMA failure defined as 
primary progression or lack of clinical benefit after a minimum of 6 cycles or unable to tolerate 
HMA due to toxicity), or who relapsed within 1 year of initial treatment (excluding those with 
favorable-risk status; see Appendix H).  
In Part B, subjects with R/R HR-MDS who are eligible include subjects who scored > 3.5 points 
in the Revised International Prognostic Scoring System (IPSS-R) [eg, IPSS-R intermediate risk (in 
combination with more than 10% bone marrow blasts or poor or very poor IPSS-R cytogenetic 
risk), IPSS-R high and IPSS-R very high risk] and are not suitable for other established therapies 
(eg, transplant or hypomethylating agent) (Appendix G).
Note that the 3.6 mg dose of CC-90009 on Days 1-5 schedule with dexamethasone premedication 
had been selected as the Part B dose and schedule in both R/R AML and R/R HR-MDS for the 
dose expansion part of the study (Part B). Due to a high rate of sepsis (75%) observed in the initial 
8 R/R AML subjects enrolled in Part B at dose level 3.6 mg Days 1-5 with dexamethasone 
premedication, the SRC recommended to close R/R AML and R/R HR-MDS cohorts receiving 
CC-90009 at 3.6 mg Days 1-5 for enrollment.
New cohorts in Part B will be enrolled at CC-90009 dose levels of 2.4 mg Days 1-7 and 3.0 mg 
Days 1-7. The selection of these doses at the Days 1-7 schedule is based primarily on PK and PD 
analysis and safety and tolerability data. These R/R AML and R/R HR-MDS subjects will be 
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CC-90009-AML-001 Amendment 9
Final: 31 Mar 2022
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pooled in each cohort by dose level for analysis of safety, PK, and PD, which will include between 
6 and 40 subjects with up to 20 subjects with R/R AML and up to 20 subjects with R/R HR-MDS
in each cohort. The cohorts will enroll subjects in parallel. Up to 6 subjects per cohort will be 
initially enrolled as a safety run-in. The SRC will assess tolerability of the dose and schedule for 
these initial subjects that completed at least one cycle of study treatment based on the Part A 
stopping criteria (Section 7.2.8) and recommend further expansion of one or more cohorts. The 
expanded cohort(s) will be monitored for the excess toxicities including sepsis utilizing the non-
binding Bayesian stopping criterion on a continuous basis (Section 9.9.3). The SRC will continue 
to review safety and preliminary efficacy data regularly throughout the study and make 
recommendations about study continuation, cohort continuation, and dose modification, as 
appropriate.
The study will be conducted in compliance with International Council for Harmonisation (ICH) of 
Technical Requirements for Pharmaceuticals for Human Use/Good Clinical Practice (GCP) and 
applicable regulatory requirements.
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Figure 1:
Study Schema for Dose-Limiting Toxicity Window in Part A (Dose Escalation)
DLT = dose-limiting toxicity.
a Modified dosing schedules (eg, increasing from 5 to 10 days) may be evaluated in additional cohorts, if necessary, based on the review by the Safety Review 
Committee of available safety and laboratory data, PK profiles, and PD findings.
b Progressive disease is defined in Section 6.4.
c In the absence of progressive disease (or relapse) or unacceptable toxicity, subjects may continue treatment with CC-90009 through Cycle 4 if they are deriving 
benefit, as judged by the Investigator (refer to Section 6.4). Additional cycles of treatment beyond Cycle 4 may be allowed after discussion with the Medical 
Monitor if the subject is demonstrating clinical benefit (stable disease or PR) and tolerating the study drug without unacceptable toxicity.
d Additional bone marrow assessment performed at the time of hematologic recovery or Day 42 (refer to Table 4, Table 31, Table 33, or Table 37).
e Eligible subjects proceed to Cycle 2.
CC-90009
Cycle 1 
Days 1-5a
Progressive 
Diseaseb
Day 28 = End 
of Cycle 1 DLT 
Assessment 
Window
Residual 
Leukemiac
Grade ≥ 3 
Neutropenia
Day 28
Bone Marrow
Assessment
Day 28 = End 
of Cycle 1 DLT 
Assessment 
Window
End of 
Treatment Visit
Cycle 2
Day 42 = End 
of Cycle 1 DLT 
Assessment 
Windowe
Extend Cycle 1 
by 2 weeks
Hypoplastic
marrow
Day 42
Bone Marrow
Assessmentd
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Final: 31 Mar 2022
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Figure 2:
Sample Dose Escalation Schemes for Part A with an NTD of 8.1 mg
Example 1
Example 2
AE = adverse event; DLT = dose-limiting toxicity; MTD = maximum tolerated dose; NTD = non-tolerated dose.
* The DMA residual solvent in the Gen 1 CC-90009 formulation must not exceed the ICH permitted daily exposure 
limit in order to proceed with dose escalation above a daily dose of 2.4 mg. Gen 2b CC-90009 formulation is 
permitted at dose levels up to 20 mg.
Escalations proceed by 100% increments with ≥1 subject cohorts until:
•
≥2 subjects experience a CC-90009-related Grade ≥2 AE in the DLT window, or
•
≥1 subject experiences a DLT within the DLT window
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Final: 31 Mar 2022
54
Figure 3:
Sample Dose Escalation with or without a Schedule Change
Daily doses of CC-90009 are listing per mg as examples only. Actual selected dose/schedules require SRC approval.
A 50% increase in total dose from the 3.0 mg dose level on the D1-5 schedule, total dose 15 mg, would be a 22.5 mg 
total dose, or a maximum of 3.2 mg per day on a D1-7 schedule, or 2.2 mg per day on a D1-10 schedule. 
Figure 4:
High Level Study Design
AML = acute myeloid leukemia; HR = higher-risk; MDS = myelodysplastic syndrome; N = number; R/R = relapsed 
or refractory 
* A non-binding Bayesian stopping criterion will be utilized to monitor the excess adverse events including sepsis 
during Part B Dose Expansion. The SRC will continue to review safety and preliminary efficacy data regularly 
throughout the study and make recommendations about study continuation and dose modification, as appropriate
(Section 3.1, Part B-Cohort Expansion).
# Up to 20 evaluable subjects with R/R AML and up to 20 evaluable subjects with R/R HR-MDS may be enrolled in 
each cohort. Each cohort will enroll up to 40 evaluable subjects. 
3.2
Study Duration for Subjects
Enrollment is expected to take approximately 62 to 68 months to complete (50 months for dose 
escalation, and approximately 12 to 18 months for expansion).  Completion of active treatment 
and post-treatment follow-up is expected to take an additional 6 to 24 months.  The entire study is 
expected to last up to approximately 6 to 8 years.
3.3
End of Trial
The End of Trial is defined as either the date of the last visit of the last subject to complete the 
post-treatment follow-up, or the date of receipt of the last data point from the last subject that is 
required for primary, secondary and/or exploratory analysis, as prespecified in the protocol, 
whichever is the later date.
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4
STUDY POPULATION
4.1
Number of Subjects
This is a multicenter, open-label study in which approximately 72 subjects were enrolled during 
Part A (dose escalation) and 10 subjects were enrolled in Part B (3.6 mg Days 1-5 of 28-day
schedule). During the Part B (dose expansion), up to approximately 20 evaluable subjects in each 
disease indication (R/R AML and R/R HR-MDS) may be enrolled in each of the planned dose 
expansion cohorts (2.4 mg and 3.0 mg Days 1–7 of 28-day schedules). Enrollment occurred at 12
sites in North America and/or Europe for Part A. Enrollment in Part B may include additional sites 
in North America and Europe. Sites that do not screen subjects may be replaced.
During Part A, no more than one subject will be enrolled per day in each dose escalation cohort.
4.2
Inclusion Criteria
Subjects must satisfy the criteria below to be enrolled in dose escalation (Part A) or dose expansion 
(Part B) of this study. 
1) Men and women ≥ 18 years of age, at the time of signing the ICD.  
2) Subject must understand and voluntarily sign an ICD prior to any study-related 
assessments/procedures being conducted.
3) Subject is willing and able to adhere to the study visit schedule and other protocol 
requirements.
4) Relapsed or refractory AML (Parts A and B) or R/R HR-MDS (Part B only) as defined by 
World Health Organization (WHO) criteria who are not suitable for other established therapies.
a) In Part A, R/R AML
b) In Part B, R/R AML including

Relapsed after allogeneic HSCT or

In second or later relapse or

Refractory to initial induction or re-induction treatment or

Refractory or relapse after HMA treatment (HMA failure defined as primary 
progression or lack of clinical benefit after a minimum of 6 cycles or unable to tolerate 
HMA due to toxicity) or

Relapsed within 1 year of initial treatment (excluding those with favorable risk based 
on cytogenetics)
c) In Part B, R/R HR-MDS (IPSS-R > 3.5 points, IPSS-R calculated during screening period):

IPSS-R intermediate risk (in combination with more than 10% bone marrow blasts or
poor or very poor IPSS-R cytogenetic risk) or

IPSS-R high or

IPSS-R very high risk
5) Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2. 
6) At least 4 weeks (from first dose) has elapsed from donor lymphocyte infusion (DLI) without 
conditioning.
7) Subjects must have the following screening laboratory values: 
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
Corrected serum Ca or free (ionized) serum Ca within normal limits (WNL).
o Corrected Ca (mg/dL) = Total Ca (mg/dL) – 0.8 (albumin [g/dL] – 4)

Total White Blood Cell count (WBC) < 25 x 109/L prior to first infusion.  Prior or 
concurrent treatment with hydroxyurea to achieve this level is allowed.

Potassium and magnesium within normal limits or correctable with supplements.

Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) or 
alanine 
aminotransferase/serum 
glutamate 
pyruvic 
transaminase 
(ALT/SGPT) 
≤2.5 x Upper Limit of Normal (ULN).

Uric acid ≤ 7.5 mg/dL (446 μmol/L).  Prior and/or concurrent treatment with hypouricemic 
agents (eg, allopurinol, rasburicase) are allowed. 

Serum bilirubin ≤1.5 x ULN.

Estimated serum creatinine clearance of ≥ 60 mL/min using the Cockcroft-Gault equation.
Measured creatinine clearance from a 24-hour urine collection is acceptable if clinically 
indicated.

INR < 1.5 x ULN and PTT < 1.5 x ULN.
8) Per the CC-90009 Pregnancy Prevention Plan (PPP) (refer to Appendix L):  

Females of childbearing potential (FCBP; refer to Section 6.2.7) must undergo pregnancy 
testing based on the frequency outlined in PPP and pregnancy results must be negative.

Unless practicing complete abstinence from heterosexual intercourse, sexually active 
FCBP must agree to use adequate contraceptive methods as specified in PPP.
o
FCBP must agree to use two reliable forms of contraception simultaneously (or to 
practice complete abstinence), without interruption, for 28 days before starting CC-
90009, throughout the entire duration of CC-90009 treatment, during dose interruptions 
and for at least 28 days after the last dose of CC-90009.
o
Complete abstinence is only acceptable in cases where this is the preferred and usual 
lifestyle of the subject.
o
Periodic abstinence (calendar ovulation, symptothermal, post-ovulation methods) and 
withdrawal are not acceptable.
Unless practicing complete abstinence from heterosexual intercourse, sexually active 
males (including those who have had a vasectomy) must use barrier contraception 
(condoms) when engaging in sexual activity with FCBP as specified in PPP.
o
Complete abstinence is only acceptable in cases where this is the preferred and usual 
lifestyle of the subject.
o
Male patients must inform their partners who are females of childbearing potential to 
use two methods of reliable contraception throughout the entire duration of treatment, 
during dose interruptions and for at least 28 days after the last dose of CC-90009, as 
specified in PPP.
Females must agree to abstain from breastfeeding or providing breast milk for the duration 
specified in the PPP. 
Males must agree not to donate semen or sperm while receiving CC-90009, during dose 
interruptions or for at least 28 days following the last dose of CC-90009, as specified in 
the PPP.
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Final: 31 Mar 2022
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All subjects must:
o
Understand that CC-90009 could have a potential teratogenic risk.
o
Agree to abstain from donating blood for the duration specified in the PPP. 
o
Be counseled about pregnancy precautions and risks of fetal exposure (refer to PPP,
Appendix L).  
4.3
Exclusion Criteria
The presence of any of the following will exclude a subject from enrollment:
1) Subjects with acute promyelocytic leukemia (APL)
2) Subjects with clinical symptoms suggesting active central nervous system (CNS) leukemia or 
known CNS leukemia.  Evaluation of cerebrospinal fluid is only required if there is clinical 
suspicion of CNS involvement by leukemia during screening.
3) Subjects with immediately life-threatening, severe complications of leukemia such as 
disseminated/uncontrolled infection, uncontrolled bleeding, and/or uncontrolled disseminated 
intravascular coagulation. 
4) Disorders or conditions disrupting normal calcium homeostasis or preventing calcium 
supplementation including:

Any known condition disrupting calcium absorption.

Clinical evidence of hypo- or hyperparathyroidism. 

Bisphosphonate or denosumab therapy within last 4 weeks prior to starting CC-90009.

Active or recent kidney stones (≤ 1 year prior to starting CC-90009). 

Serum 25-hydroxyvitamin D level < 12 ng/mL (30 nmol/L). 
5) Impaired cardiac function or clinically significant cardiac diseases, including any of the 
following:  

Left ventricular ejection fraction (LVEF) < 45% as determined by multiple gated 
acquisition (MUGA) scan or echocardiogram (ECHO).  

Complete left bundle branch or bifascicular block.  

Congenital long QT syndrome.  

Persistent or clinically meaningful ventricular arrhythmias.  

QTcF ≥ 470 msec on Screening electrocardiogram (ECG) (mean of triplicate recordings
performed ≥ 72 hours prior to Day 1).  

Unstable angina pectoris or myocardial infarction ≤ 3 months prior to starting CC-90009.  
6) Patients with prior autologous hematopoietic stem cell transplant who, in the investigator’s 
judgment, have not fully recovered from the effects of the last transplant (eg, transplant related 
side effects).
7) Prior allogeneic hematopoietic stem cell transplant (HSCT) with either standard or reduced 
intensity conditioning ≤ 6 months prior to starting CC-90009.
8) Subjects on systemic immunosuppressive therapy post HSCT at the time of screening, or with 
clinically significant graft-versus-host disease (GVHD).  The use of topical steroids for 
ongoing skin or ocular GVHD is permitted.  
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Final: 31 Mar 2022
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9) Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half-lives or 
4 weeks prior to starting CC-90009, whichever is shorter.  Hydroxyurea is allowed to control 
peripheral leukemia blasts.  
10) Leukapheresis ≤ 2 weeks prior to starting CC-90009.
11) Major surgery ≤ 2 weeks prior to starting CC-90009. Subjects must have recovered from any 
clinically significant effects of recent surgery.
12) Pregnant or nursing females.  
13) Known human immunodeficiency virus (HIV) infection. 
14) Known chronic, active hepatitis B or C (HBV/HCV) infection.  
15) Ongoing treatment with chronic, therapeutic dosing of anti-coagulants (eg, warfarin, low 
molecular weight heparin, Factor Xa inhibitors).
16) History of concurrent second cancers requiring active, ongoing systemic treatment.
17) Subject has a known allergy/hypersensitivity to calcium, calcitriol, and/or vitamin D 
supplements or any of their ingredients.
18) Subject has any significant medical condition, laboratory abnormality, or psychiatric illness 
that would prevent the subject from participating in the study.
19) Subject has any condition, including active or uncontrolled infection, or the presence of 
laboratory abnormalities, which places the subject at unacceptable risk if he/she were to 
participate in the study.
20) Subject has any condition that confounds the ability to interpret data from the study.
21) Disorders or conditions that would, in the investigator’s judgment, prevent the subject from 
receiving concomitant corticosteroids (only for dose levels of CC-90009 at or above 3.6 mg).
22) For Part B, previous SARS-CoV-2 infection within 10 days for mild or asymptomatic 
infections or 20 days for severe/critical illness prior to C1D1. Acute symptoms must have 
resolved and based on investigator assessment in consultation with the Sponsor Medical 
Monitor, there are no sequelae that would place the subject at a higher risk of receiving study 
treatment.
23) For Part B, previous COVID-19 vaccine within 14 days of C1D1. For vaccines requiring more 
than one dose, the full series (eg, both doses of a two-dose series) should be completed at least 
14 days prior to C1D1 when feasible and when a delay in C1D1 would not put the study subject 
at risk.
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Protocol CC-90009-AML-001
Celgene Corporation
CC-90009-AML-001 Amendment 9
Final: 31 Mar 2022
59
5
TABLE OF EVENTS
For a detailed description of the procedures listed, please refer to Section 6. For details regarding CC-90009 administration, please refer 
to Section 7. Procedures for Part A Cycle 1 are shown in Table 4 and Part A Cycles 2 and higher are shown in Table 5. Based on the 
Day 28 bone marrow evaluation, subjects with hypoplastic bone marrow without evidence of persistent leukemia who have Grade ≥ 3 
neutropenia will be followed for an additional 2 weeks for safety monitoring in Cycle 1 (total duration of 42 days; refer to Figure 1).
Table 4:
Table of Events for Cycle 1 in Part A (D1-5 Schedule)
Treatment Period
Cycle 1
Screening
WK1
WK2
WK3
WK4
WK5b
WK6b
Eventsa
D-28 to -1
D1
D2
D3
D4
D5
D6
D7
D8
D15
D22
D28c
D29
D36
Study Entry (Section 6.1)
Informed consent 
X
Inclusion/ exclusion criteria
X
Medical/ oncologic history 
X
Demographics 
X
IRT registration
X
X
Pregnancy risk counseling and 
contraceptive compliance 
confirmation
X
As specified in Section 6.1.1 and the PPP in Appendix L
Prior/ concomitant medications & 
procedures (Section 6.2.1)
X
X
X
X
X
X
X
X
X
X
X
X
X
CC-90009 Administration (Section 7)
Calcium, calcitriol, and vitamin D 
supplements and recording on diary 
card (refer to Section 7.2)
X (D-3 to 
D-1)
X
X
X
X
X
X
X
Xd
Xd
Xd
Provide/ review diary card
X
X
Corticosteroid administration 
(dexamethasone) 
(refer to Section 7.2) for doses 3.6 
mg and above
X
X
X
X
X
IV administration of CC-90009e
X
X
X
X
X
1.0
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Celgene Corporation
CC-90009-AML-001 Amendment 9
Final: 31 Mar 2022
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Table 4:
Table of Events for Cycle 1 in Part A (D1-5 Schedule)
Treatment Period
Cycle 1
Screening
WK1
WK2
WK3
WK4
WK5b
WK6b
Eventsa
D-28 to -1
D1
D2
D3
D4
D5
D6
D7
D8
D15
D22
D28c
D29
D36
Monitoring as inpatient 
X
X
X
X
X
Safety Assessments (Section 6)
Adverse Event Evaluation 
(Section 6.2.2)
X
X
X
X
X
X
X
X
X
X
X
X
X
Height
X
Weight (Section 6.2.3)
X
X
X
X
X
Vital Signs (Section 6.2.3)
X
Xf
Xf
Xf
Xf
Xf
X
X
X
X
X
X
X
Physical Examination (Section 6.2.4)
X
X
X
ECOG PS (Appendix D)
X
X
X
12-lead ECG (in triplicate, 
Section 6.2.5)
X (≥72 hrs 
prior to D1)
Xf
Xf
X
LVEF (ECHO/MUGA scan; 
Section 6.2.6)
X
Pregnancy testing per PPP (FCBP 
only; Section 6.2.7)
Xg
X
X
X
X
Hematology laboratory tests 
(Section 6.2.8)
X (D-14 
to -1)
X
X
X
X
X
X
X
X
X
X
X
X
G6PD (Section 6.2.8)
X
Serum chemistry laboratory tests 
(Section 6.2.8)h
X
(D-3 to -1)
Xi
Xi
Xi
X
X
X
X
X
X
X
X
X
Additional serum Ca, Mg and PTH 
tests (Section 6.2.8)h
Xj
Xj
Xj
Xj
Xj
Serum PTH, P1NP, β-CTx tests 
(Section 6.2.8)
X
X
X
X
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Protocol CC-90009-AML-001
Celgene Corporation
CC-90009-AML-001 Amendment 9
Final: 31 Mar 2022
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Table 4:
Table of Events for Cycle 1 in Part A (D1-5 Schedule)
Treatment Period
Cycle 1
Screening
WK1
WK2
WK3
WK4
WK5b
WK6b
Eventsa
D-28 to -1
D1
D2
D3
D4
D5
D6
D7
D8
D15
D22
D28c
D29
D36
Serum 25-hydroxyvitamin D level 
(Section 6.2.8)
X
X
Urine Ca/ creatinine ratio (random) 
(Section 6.2.8)
X
X
X
X
Amylase, lipase, T-cell subsets 
(CD4+ and CD8+), TSH 
(Section 6.2.8)
X
PT, INR, PTT (Section 6.2.8)k
X
Urinalysis (Section 6.2.8)
X
(D-14 to -1)
X
PK & PD Assessments
Blood, PK (Section 6.5)
Xl
X
Xl
X
Xl
X
Urine, PK (Section 6.5) selected 
subjectsr
X
Pharmacogenomics sample (eg, 
buccal cells or nail clippings), 
(Section 6.6.1)
X
Blood (whole), biomarker flow 
cytometry (Section 6.6.2)
X
(D-14 to -1)
Xl
Xl
Xl
X
X
Blood (PBMCs), PD protein and 
RNA (Section 6.6.2)
X
(D-14 to -1)
Xl
X
X
X
Blood (PBMCs), PD ex vivo 
sensitivity assays, phenotyping & 
sequencing (Section 6.6.2)
X
Blood (plasma), PD cytokines 
(Section 6.6.2)
X
(D-14 to -1)
X
X
X
X
X
1.0
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Protocol CC-90009-AML-001
Celgene Corporation
CC-90009-AML-001 Amendment 9
Final: 31 Mar 2022
62
Table 4:
Table of Events for Cycle 1 in Part A (D1-5 Schedule)
Treatment Period
Cycle 1
Screening
WK1
WK2
WK3
WK4
WK5b
WK6b
Eventsa
D-28 to -1
D1
D2
D3
D4
D5
D6
D7
D8
D15
D22
D28c
D29
D36
Bone marrow aspirate and biopsy, 
PD biomarkers & MRD (Section 
6.6.3)m
X
(D-14 to -1)
Xn
X 
(± 3d)
Efficacy 
Bone marrow aspiration and biopsy, 
complete blood counts and 
examination of peripheral blood 
smears (Section 6.4)o
X 
(D-14 
to -1)p
X 
(± 3d)
X (only 
on D42 
± 3d)q
Abbreviations:  β-CTx = beta C-terminal telopeptide; C = cycle; Ca = calcium; CD = cluster of differentiation; D = day; ECHO = echocardiogram; ECG = electrocardiogram; 
ECOG PS = Eastern Cooperative Oncology Group performance status; FCBP = females of child bearing potential; G6PD = glucose-6-phosphate dehydrogenase; hrs = hours; INR
= international normalized ratio; IRT = integrated response technology; IV = intravenous; LVEF = left ventricular ejection fraction; Mg = magnesium; MRD = Minimal Residual 
Disease; MUGA = multi-gated acquisition scan; P1NP = procollagen type 1 N-terminal propeptide; PBMC = peripheral blood mononuclear cells; PD = pharmacodynamic; PK = 
pharmacokinetic; PPP = pregnancy prevention plan; PT = prothrombin time; PTH = parathyroid hormone; PTT = partial thromboplastin time; RNA = ribonucleic acid; TSH = 
thyroid-stimulating hormone; WK = week. 
a All study visits/procedures will have a ± 2 day window and all laboratory blood samples should be drawn predose (≤ 5 hrs), unless otherwise specified in this table or Section 
6.
b Subjects with hypoplastic bone marrow without evidence of persistent AML at the Day 28 assessment who have Grade ≥ 3 neutropenia will be followed for an additional 
2 weeks for safety monitoring in Cycle 1 (total duration of 42 days; refer to Figure 1). Not all visits are shown as separate columns under Week 6, ie, Day 42 bone marrow 
assessment.
c Eligible subjects continue on to Cycle 2 (refer to Table 5).  Based on the Day 28 bone marrow evaluation, subjects with a hypoplastic bone marrow without evidence of 
persistent leukemia who have Grade ≥ 3 neutropenia will be followed for an additional 2 weeks for safety monitoring in Cycle 1.
d Supplementation may be prolonged if hypocalcemia occurs (refer to Section 7.2.13.2). Subjects are to start supplements at least 3 days prior to Day 1 of Cycle 2 as per 
Section 7.2.
e Subjects will be closely monitored during administration of CC-90009 and for at least one hour after. Subjects should be adequately hydrated to prevent potential tumor lysis 
syndrome (TLS) (eg, 2 to 3 liters of oral or IV fluids per day) starting the day prior to CC-90009 administration and continuing through each day of CC-90009 
administration. Refer to Section 7.2.12 for information on dose interruptions. The SRC may decide to evaluate alternate dosing schedules (eg, increasing from 5 to up to 
10 consecutive days of CC-90009 administration) based on their review of available clinical and laboratory safety data, PK profiles, and PD findings. 
f Multiple measurements performed on this day. 
g Two pregnancy tests (sensitivity of at least 25 mIU/mL) must be performed prior to first dose of CC-90009:  within 10 to 14 days prior and within 24 hours prior. Both tests 
must be negative for CC-90009 dosing to begin.
h A free (ionized) serum calcium test should be obtained at Screening to establish baseline values in addition to the corrected serum calcium test (corrected for albumin) used to 
fulfill the inclusion criteria. In the event of Grade ≥ 2 hypocalcemia or symptoms of hypocalcemia (eg, carpopedal spasm, tetany, seizures, etc), subjects must be hospitalized. 
1.0
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Protocol CC-90009-AML-001
Celgene Corporation
CC-90009-AML-001 Amendment 9
Final: 31 Mar 2022
63
Also, if Grade ≥ 2 hypocalcemia and abnormal levels of serum albumin occurs, a serum ionized calcium test must be performed. Refer to Section 7.2.13.2 for hypocalcemia 
management guidelines.
i
Specific tests for TLS monitoring required predose and 12 hours (± 1 hour) postdose on Days 1, 2, and 3. Refer to Section 6.2.8. 
j
Additional serum calcium/magnesium tests required 6 and 12 hours (± 1 hour) postdose on days of CC-90009 administration. Additional PTH tests required at 6 hours (± 1 
hours) post-dose on days of CC-90009 administration.
k Subsequent coagulation tests only performed for subjects on anticoagulant therapy and as clinically indicated. 
l
Multiple blood samples will be collected for this assay on the specified day. Refer to Sections 6.5 and 6.6.
m Bone marrow samples for biomarker assessment are mandatory. If bone marrow samples are scheduled to be collected on the same day for efficacy, the biomarker samples 
should be collected at the same time. If sufficient bone marrow aspirate specimen is not available, peripheral blood may be submitted in place of the BMA specimen for 
biomarker studies (eg, MRD); see laboratory manual for details.
n Obtained between 4 to 8 hours postdose. The samples may be obtained on Day 4 if necessary due to scheduling difficulties.
o Additional aspirates and biopsies will be collected as clinically indicated (eg, Cycle 1 Day 15 based on Investigator’s medical assessment). 
p Molecular and cytogenetic studies may be omitted at:  Screening, if they were completed within the previous 90 days and the results are available for recording on the electronic 
case report forms and Day 42 (or at hematologic recovery), if a complete response is documented at Day 28.  
q Additional bone marrow assessment performed at the time of hematologic recovery or Day 42 (± 3 days).  Eligible subjects continue on to Cycle 2 (refer to Table 5).
r Urine PK to be performed on approximately 10 selected subjects from Part A and/or Part B. This is a 24-hour collection that starts on C1D1 and ends on C1D2.
1.0
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Protocol CC-90009-AML-001
Celgene Corporation
CC-90009-AML-001 Amendment 9
Final: 31 Mar 2022
64
Table 5:
Table of Events for Cycles ≥ 2 in Part A (D1-5 Schedule), End of Treatment Visit, and Follow-up Period
Treatment Period
Follow-up Period
Cycles ≥ 2
WK1
WK2
WK3
WK4
EOTb
Safetyc
Eventsa
Day 1
Day 2
Day 3
Day 4
Day 5
Day 8
Day 15
Day 22
Day 28
≤ 28 days
28 days 
(± 3 days)
Long 
Term
Review concomitant medications & 
procedures (Section 6.2.1)
X
X
X
X
X
X
X
X
X
X
CC-90009 Administration (Section 7)
Calcium, calcitriol and Vitamin D 
supplements and recording on diary card 
(Section 7.2)
X
X
X
X
Xd
Xd
X (C2 
and C3)d
Provide/ review of diary card
X
X
Corticosteroid administration 
(dexamethasone) (refer to Section 7.2) for 
doses 3.6 mg and above
X
X
X
X
X
IV administration of CC-90009e
X
X
X
X
X
Safety Assessments (Section 6)
Adverse Event Evaluation (Section 6.2.2)
X
X
X
X
X
X
X
X
X
X
Weight (Section 6.2.3)
X
X
Vital Signs (Section 6.2.3)
Xf
Xf
Xf
Xf
Xf
X
X
X
X
Physical Examination (Section 6.2.4)
X
X
ECOG PS (Appendix D)
X
X
12-lead ECG (Section 6.2.5)g
X
X
LVEF (ECHO/MUGA; Section 6.2.6)
X (only 
C2 ± 7d)
X (± 7d)h
Pregnancy test (FCBP only; Section 6.2.7) 
X
Xi
Xi
Xi
Pregnancy risk counseling and contraceptive 
compliance confirmation 
X
As specified in Section 6.1.1 and the PPP in Appendix L
Hematology laboratory (Section 6.2.8)
X
X
X
X
X
X
X
X
X
1.0
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Protocol CC-90009-AML-001
Celgene Corporation
CC-90009-AML-001 Amendment 9
Final: 31 Mar 2022
65
Table 5:
Table of Events for Cycles ≥ 2 in Part A (D1-5 Schedule), End of Treatment Visit, and Follow-up Period
Treatment Period
Follow-up Period
Cycles ≥ 2
WK1
WK2
WK3
WK4
EOTb
Safetyc
Eventsa
Day 1
Day 2
Day 3
Day 4
Day 5
Day 8
Day 15
Day 22
Day 28
≤ 28 days
28 days 
(± 3 days)
Long 
Term
Serum chemistry laboratory tests 
(Section 6.2.8)j
X
X
X
X
X
X
Serum Ca & Mg tests (Section 6.2.8)j
Xj
Xj
Xj
Xj
Xj
Serum PTH, P1NP, β-CTx tests 
(Section 6.2.8)
X
X
X
Serum 25-hydroxyvitamin D level 
(Section 6.2.8)
X
Urine Ca/ creatinine ratio test (random) 
(Section 6.2.8)
X
X
X
Amylase, lipase, T-cell subsets (CD4+ and 
CD8+), TSH (Section 6.2.8)
X
X
PT, INR, PTT (for subjects on anticoagulant 
therapy) (Section 6.2.8)
X
X
Urinalysis (Section 6.2.8)
X
X
PK & PD Assessments
Blood, PK (Section 6.5)o
X
X
X
X
Xo
Blood (whole), biomarker flow cytometry, 
(Section 6.6.2) first cycle of intra-subject 
dose escalation onlyk
Xk
Xk
Xk
Xk
Xk
Blood (PBMCs), PD protein and RNA 
(Section 6.6.2) first cycle of intra-subject 
dose escalation onlyk
Xk
Xk
Xk
Xk
Blood (plasma), PD cytokines 
(Section 6.6.2) first cycle of intra-subject 
dose escalation onlyk
X
X
X
X
X
1.0
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930183898
14.0
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CC-90009
Protocol CC-90009-AML-001
Celgene Corporation
CC-90009-AML-001 Amendment 9
Final: 31 Mar 2022
66
Table 5:
Table of Events for Cycles ≥ 2 in Part A (D1-5 Schedule), End of Treatment Visit, and Follow-up Period
Treatment Period
Follow-up Period
Cycles ≥ 2
WK1
WK2
WK3
WK4
EOTb
Safetyc
Eventsa
Day 1
Day 2
Day 3
Day 4
Day 5
Day 8
Day 15
Day 22
Day 28
≤ 28 days
28 days 
(± 3 days)
Long 
Term
Bone marrow aspirate and biopsy, PD 
biomarkers & MRD (Section 6.6.3)l, m
X (C2 
and C4; 
± 3d)
Xn
Refer to 
Section 
6.3.2
Efficacy 
Complete blood counts and examination of 
peripheral blood smears (Section 6.4)m
X (C2 
and C4; 
± 3d)
Xn
Refer to 
Section 
6.3.2
Bone marrow aspirate and biopsy 
(Section 6.4)m
X (C2 
and C4; 
± 3d)
Xn
Refer to 
Section 
6.3.2
Follow-up 
CC-90009-related AE/SAE follow-up
Refer to Section 6.3.1
Anticancer therapies 
Refer to Section 6.3.2
Survival 
Refer to Section 6.3.3
Abbreviations:  Adverse event = AE; β-CTx = beta C-terminal telopeptide; C = cycle; Ca = calcium; CD = cluster of differentiation; D = day; ECHO = echocardiogram; ECG = 
electrocardiogram; ECOG PS = Eastern Cooperative Oncology Group performance status; EOT = End of Treatment; FCBP = females of child bearing potential; INR = international 
normalized ratio; IV = intravenous; LVEF = left ventricular ejection fraction; Mg = magnesium; MUGA = multi-gated acquisition scan; P1NP = procollagen type 1 N-terminal 
propeptide; PD = pharmacodynamics; PPP = pregnancy prevention plan; PT = prothrombin time; PTH = parathyroid hormone; PTT = partial thromboplastin time; q = every; SAE 
= serious adverse event; TSH = thyroid-stimulating hormone; WK = week. 
a All study visits/procedures will have a ± 2 day window and all laboratory blood samples should be drawn predose (≤ 5 hrs), unless otherwise specified in this table or Section
6. Cycles should start ≤ 7 days after the last day of the previous cycle.
b EOT Visit performed within 28 days after last dose of CC-90009 for subjects that discontinue prior to completing dosing in Cycle 4. For subjects that complete dosing in Cycle 
4, this visit should be completed on Day 28 (± 2 days) of Cycle 4. For subjects who complete dosing after Cycle 4, EOT Visit should be completed within 28 days after the 
last day of the previous cycle. 
c Safety Follow-up Visit is performed 28 days (± 3 days) after the last dose of CC-90009 for all subjects. May be performed by telephone contact if pregnancy testing is not 
required (refer to footnote “i”).
d Supplements to be administered for at least 3 days after the last dose in each cycle. Supplementation may be prolonged if hypocalcemia occurs (refer to Section 7.2.13.2). 
Subjects to start supplements at least 3 days prior to Day 1 of Cycles 3 and 4 as per Section 7.2.
1.0
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Protocol CC-90009-AML-001
Celgene Corporation
CC-90009-AML-001 Amendment 9
Final: 31 Mar 2022
67
e Subjects will be closely monitored during the administration of CC-90009 and for at least 1 hour after. Subjects should be adequately hydrated to prevent potential tumor lysis 
syndrome (TLS) (eg, 2 to 3 liters of oral or IV fluids per day) starting the day prior to CC-90009 administration and continuing through each day of CC-90009 
administration. Refer to Section 7.2.12 for information on dose interruptions. The SRC may decide to evaluate alternate dosing schedules (eg, increasing from 5 to up to 
10 consecutive days of CC-90009 administration) based on their review of available clinical and laboratory safety data, PK profiles, and PD findings. Subjects should be 
administered Cycle ≥ 2 of CC-90009 in a Limited Stay Unit (LSU) or as inpatient. Subjects experiencing Grade ≥ 2 hypocalcemia during any cycle should be administered 
CC-90009 in the inpatient setting for subsequent cycles (an exception can be made for subjects with grade 2 hypocalcemia lasting less than 24 hours that recovers without IV 
calcium [eg, calcium gluconate or calcium chloride] after discussion with the Celgene medical monitor).
f Multiple measurements performed on this day. 
g Triplicate ECGs will be performed on Day 1 of each cycle (refer to Section 6.2.5) and a single ECG obtained at the EOT visit. 
h The EOT Visit LVEF is not required if the prior LVEF was performed within 56 days.
i
Per the PPP, a pregnancy test is required 28 days after the last dose of for all FCBP. For FCBP with irregular menstrual periods, a pregnancy test is required every 14 days (ie, 
Day 15 of Cycles ≥2 and at 14 and 28 days after the last dose of CC-90009).
j
In the event of Grade ≥ 2 hypocalcemia or symptoms of hypocalcemia (eg, carpopedal spasm, tetany, seizures, etc), subjects must be hospitalized. Also, if Grade ≥ 2 
hypocalcemia and abnormal levels of serum albumin occurs, a serum ionized calcium test must be performed. Refer to Section 7.2.13.2 for hypocalcemia management 
guidelines. Refer to Section 6.2.8 for required days and timing of tests. Subjects who experienced Grade ≥ 2 hypocalcemia during Cycle 1, require testing Days 1-5 at 6 and 
12 hours postdose. All other subjects require testing prior to dosing. If intra-subject dose escalation occurs, subjects should be treated as in Cycle 1.
k If intra-subject dose escalation occurs, blood samples for PD assays will be collected during the first cycle only at the increased dose; see laboratory manual for details. Multiple 
blood samples will be collected for this assay on the specified Days 1, 2, 3. Refer to Section 6.6. 
l
Bone marrow samples for biomarker PD assessment are mandatory. When applicable (refer to time points in the table above), bone marrow samples for biomarker PD 
assessment will be obtained at the same time as a scheduled efficacy assessment. If sufficient bone marrow aspirate specimen is not available, peripheral blood may be 
submitted in place of the BMA specimen for biomarker studies (eg, MRD); see laboratory manual for details.
m If end of Cycle 2 (Day 28 ± 3 days) samples are obtained on Day 1 of Cycle 3, they must be obtained prior to CC-90009 administration. Additionally, bone marrow aspirates 
and biopsies may be obtained in both Part A and Part B, after a CR is confirmed, if relapse is suspected, or following treatment discontinuation to elucidate effects of long-
term treatment or resistance mechanisms. Additional aspirates and biopsies will be collected as clinically indicated based on the Investigator’s medical assessment.
n For subjects that complete dosing in Cycle 4, performed/obtained once on Day 28 (± 3 days). For subjects that continue (after consultation with Medical Monitor) beyond 
Cycle 4, efficacy and bone marrow PD assessments may be obtained to confirm a CR, if relapse is suspected, or following treatment discontinuation to elucidate effects of 
long-term treatment or resistance mechanisms. Additional aspirates and biopsies will be collected as clinically indicated based on the Investigator’s medical assessment. Refer 
to Section 6.3.2 and Section 6.4.
o
Blood samples for PK are to be collected in Cycle 2 only; on Day 5 there is a pre-dose and 24 hour postdose sample Section 6.5.1.
Tables of Events for the alternate dosing schedules (eg, D1-3/D8-10 Dosing Schedules, D1-7 Dosing Schedule, and D1-10 Dosing 
Schedule) are located in Appendix K and Appendices M-O. All new dose levels (including dosing schedule changes) require prior 
approval from the SRC before use (Section 3.1). Procedures for Part B (D1-5 Schedule) Cycle 1 are shown in Table 6 and Part B (D1-
5 Schedule) Cycles 2 and higher are shown in Table 7.
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Final: 31 Mar 2022
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Table 6:
Table of Events for Cycle 1 in Part B (D1-5 Schedule)
Eventsa
Treatment Period
Cycle 1
Screening
WK1
WK2
WK3
WK4
D-28 to -1
D1
D2
D3
D4
D5
D6
D7
D8
D15
D22
D28c
Study Entry (Section 6.1)
Informed consent 
X
Inclusion/ exclusion criteria
X
Medicalt/ oncologic history 
X
AML or MDS Disease Assessment and 
Cohort Assignmentb
X
Demographics 
X
IRT registration
X
X
Pregnancy risk counseling and 
contraceptive compliance confirmation
X
As specified in Section 6.1.1 and the PPP in Appendix L
Prior/ concomitant medications & 
procedures (Section 6.2.1)
X
X
X
X
X
X
X
X
X
X
X
CC-90009 Administration (Section 7)
Calcium, calcitriol, and vitamin D 
supplements and recording on diary card 
(refer to Section 7.2)
X (D-3 to 
D-1)
X
X
X
X
X
X
X
Xd
Provide/review diary card
X
X
Corticosteroid administration 
(dexamethasone) (refer to Section 7.2) 
for doses 3.6 mg and above
X
X
X
X
X
IV administration of CC-90009
X
X
X
X
X
Monitoring as an inpatient
X
X
X
X
X
Safety Assessments (Section 6)
Adverse Event Evaluation (Section 6.2.2)
X
X
X
X
X
X
X
X
X
X
X
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Final: 31 Mar 2022
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Table 6:
Table of Events for Cycle 1 in Part B (D1-5 Schedule)
Eventsa
Treatment Period
Cycle 1
Screening
WK1
WK2
WK3
WK4
D-28 to -1
D1
D2
D3
D4
D5
D6
D7
D8
D15
D22
D28c
Height
X
Weight (Section 6.2.3)
X
X
X
X
X
Vital Signs (Section 6.2.3)
X
Xf
Xf
Xf
Xf
Xf
X
X
X
X
X
Physical Examination (Section 6.2.4)
X
X
X
ECOG PS (Appendix D)
X
X
X
SARS-CoV-2 Viral Testingr
X (within 
7 days of 
D1)
12-lead ECG (in triplicate, Section 6.2.5)
X (≥72 
hrs prior 
to D1)
Xf
Xf
X
LVEF (ECHO/MUGA scan; 
Section 6.2.6)
X
Pregnancy testing per PPP (FCBP only; 
Section 6.2.7)
Xg
X
X
X
Hematology laboratory tests 
(Section 6.2.8)
X (D-14 
to -1)
X
X
X
X
X
X
X
X
X
X
G6PD (Section 6.2.8)
X
Serum chemistry laboratory tests 
(Section 6.2.8)h
X
(D-3 
to -1)
Xi
Xi
Xi
X
X
X
X
X
Additional serum Ca, Mg and PTH tests 
(Section 6.2.8)h
Xj
Xj
Xj
Xj
Xj
Serum 25-hydroxyvitamin D level 
(Section 6.2.8)
X
X
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Final: 31 Mar 2022
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Table 6:
Table of Events for Cycle 1 in Part B (D1-5 Schedule)
Eventsa
Treatment Period
Cycle 1
Screening
WK1
WK2
WK3
WK4
D-28 to -1
D1
D2
D3
D4
D5
D6
D7
D8
D15
D22
D28c
Serum PTH test
Urine Ca/ creatinine ratio (random) 
(Section 6.2.8)
X
X
X
X
Serum P1NP and β-CTx tests 
(Section 6.2.8)
X
X
Amylase, lipase, T-cell subsets (CD4+ 
and CD8+), TSH (Section 6.2.8)
X
PT, INR, PTT (Section 6.2.8)k
X
Urinalysis (Section 6.2.8)
X (D-14 
to -1)
X
PK & PD Assessments
Blood, PK (Section 6.5)
Xl
X
Urine, PK (Section 6.5) selected 
subjectsq
X
Pharmacogenomics sample (eg, buccal 
cells or nail clippings), (Section 6.6.1)
X
SARS-CoV-2 serologys (Section 6.6.4)
X
Blood (whole), biomarker flow 
cytometry (Section 6.6.2)
X (D-14 
to -1)
Xl
Xl
X
X
Blood (whole), PD biomarker (Section 
6.6.2)
X (D-14 
to -1)
Xn
X 
(± 3d)
Blood (PBMCs), PD protein and RNA 
(Section 6.6.2)
X (D-14 
to -1)
X
X
X
Blood (PBMCs), PD ex vivo sensitivity 
assays, phenotyping & sequencing 
(Section 6.6.2)
X
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Final: 31 Mar 2022
71
Table 6:
Table of Events for Cycle 1 in Part B (D1-5 Schedule)
Eventsa
Treatment Period
Cycle 1
Screening
WK1
WK2
WK3
WK4
D-28 to -1
D1
D2
D3
D4
D5
D6
D7
D8
D15
D22
D28c
Blood (plasma), PD cytokines 
(Section 6.6.2)
X (D-14 
to -1)
X
X
X
X
X
Bone marrow aspirate and biopsy, PD 
biomarkers & MRD (Section 6.6.3)m
X (D-14 
to -1)
Xn
X 
(± 3d)
Bone marrow aspiration and biopsy, 
complete blood counts and examination 
of peripheral blood smears (Section 6.4)o
X (D-14 
to -1)p
X 
(± 3d)
Abbreviations:  β-CTx = beta C-terminal telopeptide; C = cycle; Ca = calcium; CD = cluster of differentiation; D = day; ECHO = echocardiogram; ECG = electrocardiogram; ECOG 
PS = Eastern Cooperative Oncology Group performance status; FCBP = females of child bearing potential; G6PD = glucose-6-phosphate dehydrogenase; hrs = hours; INR = 
international normalized ratio; IRT = integrated response technology; IV = intravenous; LVEF = left ventricular ejection fraction; Mg = magnesium; MRD = Minimal Residual 
Disease; MUGA = multi-gated acquisition scan; P1NP = procollagen type 1 N-terminal propeptide; PBMC = peripheral blood mononuclear cells; PD = pharmacodynamics; 
PK = pharmacokinetic; PPP = pregnancy prevention plan; PT = prothrombin time; PTH = parathyroid hormone; PTT = partial thromboplastin time; RNA = ribonucleic acid; RT-
PCR = reverse transcriptase polymerase chain reaction; SARS-CoV-2 = severe acute respiratory syndrome coronavirus; TSH = thyroid-stimulating hormone; WK = week.
a All study visits/procedures will have a ± 2 day window and all laboratory blood samples should be drawn predose (≤ 5 hrs), unless otherwise specified in this table or Section 6.
b See Section 6.1 for details regarding collecting BMA/BMB, PBS, and cytogenetics at screening for assessing AML/MDS diagnosis, for potential retrospective confirmation of 
mutational status, and collecting BMA and PB at screening for pharmacodynamics and correlative studies. A bone marrow biopsy can be collected in conjunction with an aspirate 
if it is standard institutional practice.  A bone marrow biopsy must be collected if adequate aspirate sample is not attainable.
c Eligible subjects continue on to Cycle 2 (refer to Table 7).  
d Supplementation may be prolonged if hypocalcemia occurs (refer to Section 7.2.13.2). Subjects are to start supplements at least 3 days prior to Day 1 of Cycle 2 as per Section 7.2.
e Subjects will be closely monitored during administration of CC-90009 and for at least one hour after. Subjects should be adequately hydrated to prevent potential tumor lysis 
syndrome (TLS) (eg, 2 to 3 liters of oral or IV fluids per day) starting the day prior to CC-90009 administration and continuing through each day of CC-90009 administration. Refer 
to Section 7.2.12 for information on dose interruptions. The SRC may decide to evaluate alternate dosing schedules (eg, increasing from 5 to up to 10 consecutive days of CC-
90009 administration) based on their review of available clinical and laboratory safety data, PK profiles, and PD findings. 
f Multiple measurements performed on this day. 
g Two pregnancy tests (sensitivity of at least 25 mIU/mL) must be performed prior to first dose of CC-90009:  within 10 to 14 days prior and within 24 hours prior. Both tests must 
be negative for CC-90009 dosing to begin. 
h A free (ionized) serum calcium test should be obtained at Screening to establish baseline values in addition to the corrected serum calcium test (corrected for albumin) used to 
fulfill the inclusion criteria. In the event of Grade ≥ 2 hypocalcemia or symptoms of hypocalcemia (eg, carpopedal spasm, tetany, seizures, etc), subjects must be hospitalized. 
Also, if Grade ≥ 2 hypocalcemia and abnormal levels of serum albumin occurs, a serum ionized calcium test must be performed. Refer to Section 7.2.13.2 for hypocalcemia 
management guidelines.
i
Specific tests for TLS monitoring required predose and 12 hours (± 1 hour) postdose on Days 1, 2, and 3. Refer to Section 6.2.8. 
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Final: 31 Mar 2022
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j
Additional serum calcium/magnesium tests required 6 and 12 hours (± 1 hour) postdose on days of CC-90009 administration. Additional PTH tests required at 6 hours (± 1 hours) 
post-dose on days of CC-90009 administration.
k Subsequent coagulation tests only performed for subjects on anticoagulant therapy and as clinically indicated.
l
Multiple blood samples will be collected for this assay on the specified day. Refer to Sections 6.5 and 6.6.
m Bone marrow samples for biomarker assessment are mandatory. If bone marrow samples are scheduled to be collected on the same day for efficacy, the biomarker samples should 
be collected at the same time. If sufficient bone marrow aspirate specimen is not available, peripheral blood may be submitted in place of the BMA specimen for biomarker studies 
(eg, MRD); see laboratory manual for details.
n Obtained between 4 to 8 hours postdose. The samples may be obtained on Day 4 if necessary due to scheduling difficulties. 
o Additional aspirates and biopsies will be collected as clinically indicated (eg, Cycle 1 Day 15 based on Investigator’s medical assessment). 
p Molecular and cytogenetic studies may be omitted at:  Screening, if they were completed within the previous 90 days and the results are available for recording on the electronic 
case report forms; see Section 6.1 for details on sending samples to the central laboratory.  
q Urine PK to be performed on approximately 10 selected subjects from Part A and/or Part B.  This is a 24-hour collection that starts C1D1 and ends C1D2.
r RT-PCR testing for SARS-CoV-2 is mandatory within 7 days prior to first dose of CC-90009 (C1D1). The RT-PCR test should be based on institutional or local guidelines. Please 
see Section 6.1 in the event of a positive result.
s Serum will be collected at predose on Cycle 1 Day 1 (or at screening), approximately every 6 months during study treatment and at EOT to be used for possible measurements of 
anti-SARS-CoV-2 serology (anti-SARS-CoV-2 total or IgG). Results will not be used to determine eligibility. Serum should also be collected approximately 4 weeks after a 
documented or suspected SARS-CoV-2 infection.
t Medical history will also include COVID-19 vaccines, toxicities of prior treatments, and known allergies. 
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Final: 31 Mar 2022
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Table 7:
Table of Events for Cycles ≥ 2 in Part B (D1-5 Schedule), End of Treatment Visit, and Follow-up Period
Eventsa
Treatment Period
Follow-up Period
Cycles ≥ 2
Safetyc
Long 
Term
WK1
WK2
WK3
WK4
EOTb
Day 1
Day 2
Day 3
Day 4
Day 5
Day 8
Day 15
Day 22
Day 28
≤ 28 days
28 days 
(± 3 days)
Review concomitant medications & 
procedures (Section 6.2.1)
X
X
X
X
X
X
X
X
X
X
X
CC-90009 Administration (Section 7)
Calcium, calcitriol and Vitamin D 
supplements and recording on diary 
card (Section 7.2)
X
X
X
X
Xd
Xd
X (C2 and 
C3)d
Provide/ review of diary card
X
X
Corticosteroid administration 
(dexamethasone) (refer to Section 7.2) 
for doses 3.6 mg and above
X
X
X
X
X
IV administration of CC-90009e
X
X
X
X
X
Safety Assessments (Section 6)
Adverse Event Evaluation (Section 
6.2.2)
X
X
X
X
X
X
X
X
X
X
Weight (Section 6.2.3)
X
X
Vital Signs (Section 6.2.3)
Xf
Xf
Xf
Xf
Xf
X
X
X
X
Physical Examination (Section 6.2.4)
X
X
ECOG PS (Appendix D)
X
X
12-lead ECG (Section 6.2.5)g
X
X
LVEF (ECHO/MUGA; Section 6.2.6)
X 
(only 
C2 ± 
7d)
X (± 7d)h
Pregnancy test (FCBP only; 
Section 6.2.7) 
X
Xi
Xi
Xi
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Final: 31 Mar 2022
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Table 7:
Table of Events for Cycles ≥ 2 in Part B (D1-5 Schedule), End of Treatment Visit, and Follow-up Period
Eventsa
Treatment Period
Follow-up Period
Cycles ≥ 2
Safetyc
Long 
Term
WK1
WK2
WK3
WK4
EOTb
Day 1
Day 2
Day 3
Day 4
Day 5
Day 8
Day 15
Day 22
Day 28
≤ 28 days
28 days 
(± 3 days)
Pregnancy risk counseling and 
contraceptive compliance confirmation
X
As specified in Section 6.1.1 and the PPP in Appendix L
Hematology laboratory (Section 6.2.8)
X
X
X
X
X
X
X
X
X
Serum chemistry laboratory tests 
(Section 6.2.8)j
X
X
X
X
X
X
Serum Ca & Mg tests (Section 6.2.8)j
Xj
Xj
Xj
Xj
Xj
Serum PTH test (Section 6.2.8)
X
X
X
Serum P1NP and β-CTx tests 
(Section 6.2.8)
X
X
Serum 25-hydroxyvitamin D level 
(Section 6.2.8)
X
Urine Ca/ creatinine ratio test 
(random) (Section 6.2.8)
X
X
X
Amylase, lipase, T-cell subsets (CD4+ 
and CD8+), TSH (Section 6.2.8)
X
X
PT, INR, PTT (for subjects on 
anticoagulant therapy) (Section 6.2.8)
X
X
Urinalysis (Section 6.2.8)
X
X
PK & PD Assessments
Blood, PK (Section 6.5)o
Xo
Xo
Blood (whole), PD biomarker (Section 
6.6.2)
X (C2 and 
C4; ± 3d)
Xn
Refer to 
Section 
6.3.2
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Final: 31 Mar 2022
75
Table 7:
Table of Events for Cycles ≥ 2 in Part B (D1-5 Schedule), End of Treatment Visit, and Follow-up Period
Eventsa
Treatment Period
Follow-up Period
Cycles ≥ 2
Safetyc
Long 
Term
WK1
WK2
WK3
WK4
EOTb
Day 1
Day 2
Day 3
Day 4
Day 5
Day 8
Day 15
Day 22
Day 28
≤ 28 days
28 days 
(± 3 days)
Bone marrow aspirate and biopsy, PD 
biomarkers & MRD (Section 6.6.3)l, m
X (C2 and 
C4; ± 3d)
Xn
Refer to 
Section 
6.3.2
SARS-CoV-2 Serologyp
(Section 6.6.4)
Serum collected every 6 months during study treatment (eg, C6D1, C12D1, etc)
X
Efficacy
Complete blood counts and 
examination of peripheral blood 
smears (Section 6.4)m
X (C2 and 
C4; ± 3d)
Xn
Refer to 
Section 
6.3.2
Bone marrow aspirate and/or biopsy 
(Section 6.4)m
X (C2 and 
C4; ± 3d)
Xn
Refer to 
Section 
6.3.2
Follow-up
CC-90009-related AE/SAE follow-up
Refer to Section 6.3.1
Anticancer therapies 
Refer to Section 6.3.2
Survival 
Refer to Section 6.3.3
Transformation to AML for MDS 
After signing ICF and until death, lost to follow-up, withdrawal of consent for further data collection, or end of trial.
Abbreviations:  Adverse event = AE; AML = acute myeloid leukemia; β-CTx = beta C-terminal telopeptide; C = cycle; Ca = calcium; CD = cluster of differentiation; D = day; 
ECHO = echocardiogram; ECG = electrocardiogram; ECOG PS = Eastern Cooperative Oncology Group performance status; EOT = End of Treatment; FCBP = females of child 
bearing potential; INR = international normalized ratio; IV = intravenous; LVEF = left ventricular ejection fraction; MDS = myelodysplastic syndromes; Mg = magnesium; MUGA 
= multi-gated acquisition scan; P1NP = procollagen type 1 N-terminal propeptide; PD = pharmacodynamic; PK = pharmacokinetic; PPP = pregnancy prevention plan; PT = 
prothrombin time; PTH = parathyroid hormone; PTT = partial thromboplastin time; q = every; SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome 
coronavirus 2; TSH = thyroid-stimulating hormone; WK = week. 
a All study visits/procedures will have a ± 2 day window and all laboratory blood samples should be drawn predose (≤ 5 hrs), unless otherwise specified in this table or Section 6. 
Cycles should start ≤ 7 days after the last day of the previous cycle. 
b EOT Visit performed within 28 days after last dose of CC-90009 for subjects that discontinue prior to completing dosing in Cycle 4. For subjects that complete dosing in Cycle 4, 
this visit should be completed on Day 28 (± 2 days) of Cycle 4.  For subjects who complete dosing after Cycle 4, EOT Visit should be completed within 28 days after the last day 
of the previous cycle. 
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c Safety Follow-up Visit is performed 28 days (± 3 days) after the last dose of CC-90009 for all subjects. May be performed by telephone contact if pregnancy testing is not required 
(refer to footnote “i”). 
d
Supplements to be administered for at least 3 days after the last dose in each cycle. Supplementation may be prolonged if hypocalcemia occurs (refer to Section 7.2.13.2). Subjects 
to start supplements at least 3 days prior to Day 1 of Cycles 3 and 4 as per Section 7.2.
e Subjects will be closely monitored during the administration of CC-90009 and for at least 1 hour after. Subjects should be adequately hydrated to prevent potential tumor lysis 
syndrome (TLS) (eg, 2 to 3 liters of oral or IV fluids per day) starting the day prior to CC-90009 administration and continuing through each day of CC-90009 administration. Refer 
to Section 7.2.12 for information on dose interruptions. The SRC may decide to evaluate alternate dosing schedules (eg, increasing from 5 to up to 10 consecutive days of CC-
90009 administration) based on their review of available clinical and laboratory safety data, PK profiles, and PD findings. Subjects should be administered Cycle ≥ 2 of CC-90009 
in a Limited Stay Unit (LSU) or as inpatient. Subjects experiencing Grade ≥ 2 hypocalcemia during any cycle should be administered CC-90009 in the inpatient setting for 
subsequent cycles (an exception can be made for subjects with grade 2 hypocalcemia lasting less than 24 hours that recovers without IV calcium [eg, calcium gluconate or calcium 
chloride] after discussion with the Celgene medical monitor).
f Multiple measurements performed on this day. For subjects who are administered as in-patient in Cycles ≥ 2, on days that CC-90009 is administered, vital signs will be obtained 
prior to dosing (≤3 hours), and 60 minutes (± 15 minutes) and 6 hours (± 1 hr) after the end of the administration of the dose. Starting in Cycle 2 in the outpatient setting, vital 
signs will be obtained prior to dosing (≤3 hours) and at 60 minutes (± 15 minutes) after the end of the administration of the dose. Additional vital signs should be obtained as 
clinically indicated per the Investigator’s medical assessment.
g Triplicate ECGs will be performed on Day 1 of each cycle (refer to Section 6.2.5) and a single ECG obtained at the EOT visit. 
h The EOT Visit LVEF is not required if the prior LVEF was performed within 56 days. 
i
Per the PPP, a pregnancy test is required 28 days after the last dose of for all FCBP. For FCBP with irregular menstrual periods, a pregnancy test is required every 14 days (ie, 
Day 15 of Cycles ≥ 2 and at 14 and 28 days after the last dose of CC-90009).
j
In the event of Grade ≥ 2 hypocalcemia or symptoms of hypocalcemia (eg, carpopedal spasm, tetany, seizures, etc), subjects must be hospitalized. Also, if Grade ≥ 2 hypocalcemia 
and abnormal levels of serum albumin occurs, a serum ionized calcium test must be performed. Refer to Section 7.2.13.2 for hypocalcemia management guidelines. Refer to 
Section 6.2.8 for required days and timing of tests. Subjects who experienced Grade ≥ 2 hypocalcemia during Cycle 1, require testing Days 1-5 at 6 and 12 hours postdose. All 
other subjects require testing prior to dosing. 
k If intra-subject dose escalation occurs, blood samples for PD assays will be collected during the first cycle only at the increased dose; see laboratory manual for details. Multiple 
blood samples will be collected for this assay on the specified Days 1, 2, 5. Refer to Section 6.6. 
l
Bone marrow samples for biomarker PD assessment are mandatory. When applicable (refer to time points in the table above), bone marrow samples for biomarker PD assessment 
will be obtained at the same time as a scheduled efficacy assessment. If sufficient bone marrow aspirate specimen is not available, peripheral blood may be submitted in place of 
the BMA specimen for biomarker studies (eg, MRD); see laboratory manual for details. A bone marrow biopsy can be collected in conjunction with an aspirate if it is standard 
institutional practice. A bone marrow biopsy must be collected if adequate aspirate sample is not attainable; see for details on sending samples to the central laboratory for disease 
assessment.
m If end of Cycle 2 (Day 28 ± 3 days) samples are obtained on Day 1 of Cycle 3, they must be obtained prior to CC-90009 administration. Additionally, bone marrow aspirates and 
biopsies may be obtained after a CR is confirmed, if relapse is suspected, or following treatment discontinuation to elucidate effects of long-term treatment or resistance 
mechanisms. Additional aspirates and biopsies will be collected as clinically indicated based on the Investigator’s medical assessment.
n For subjects that complete dosing in Cycle 4, performed/obtained once on Day 28 (± 3 days). For subjects that continue (after consultation with Medical Monitor) beyond Cycle 
4, efficacy and bone marrow PD assessments may be obtained to confirm a CR, if relapse is suspected, or following treatment discontinuation to elucidate effects of long-term 
treatment or resistance mechanisms. Additional aspirates and biopsies will be collected as clinically indicated based on the Investigator’s medical assessment. Refer to Section 
6.3.2 and Section 6.4.
o Predose blood sample for both intensive and sparse sampling schedule in Cycles 2-4. Refer to Sections 6.5 and 6.6.
p Serum will be collected approximately every 6 months during study treatment and at EOT to be used for possible measurements of anti-SARS-CoV-2 serology (anti-SARS-CoV-
2 total or IgG). Serum should also be collected approximately 4 weeks after a documented or suspected SARS-CoV-2 infection.
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6
PROCEDURES
Any questions regarding the protocol should be directed to the Celgene Medical Monitor or 
designee. The procedures conducted for each subject enrolled in the study are outlined in Table 4
and Table 5 for Part A and Table 6 and Table 7 for Part B. All study visits will have a ± 2 day 
window unless otherwise specified below or in the Table of Events. All laboratory blood samples 
should be drawn predose unless otherwise specified (eg, PK samples). For subjects enrolled on an 
alternate schedule (eg, D1-3/D8-10, D1-7, or D1-10 dosing schedules), please refer to Table of 
Events in Appendix K and Appendices M-O.
The study procedures should be recorded in the source document and the electronic case report 
forms (eCRF). In the event subjects fail Screening, minimal information will be documented on 
the eCRFs, per database instructions.
6.1
Screening Period
The Screening window starts 28 days prior to first dose of CC-90009.  Refer to Table 4 –Table 7,
this section, and Section 6.2 for detailed information on procedures performed and the schedule.  
For subjects enrolled on an alternate schedule (eg, D1-3/D8-10, D1-7, or D1-10), please refer to 
Table of Events in Appendix K and Appendices M-O.
Waivers to the protocol will not be granted during the conduct of this trial, under any 
circumstances.
Safety laboratory analyses will be performed locally. Screening laboratory values must 
demonstrate subject eligibility, but may be repeated within the screening window, if necessary.
The ICD will be administered at the Screening visit to all subjects by qualified study staff.  It must 
be signed and dated by the subject and the administering staff prior to the start of any other study 
procedures and its completion documented in source documents and in the eCRF.  All screening 
tests and procedures must be completed within 28 days prior to the first dose of CC-90009
according to the schedule shown in Table 4, Table 6, Table 31, Table 33, Table 35, and Table 37.  
Adequate contraceptive methods as specified in the CC-90009 PPP (refer to Appendix L) must be 
used for at least 28 days before starting CC-90009, while participating in the study, during dose 
interruptions, and for at least 28 days for FCBP and 28 days for males after the last dose of CC-
90009.  The PPP applies to all subjects receiving CC-90009 therapy and will be given to sites as a 
separate document. Subjects will be counseled about appropriate contraception during Screening 
(refer to Section 6.1.1).  Counseling should be documented in source documents.
The following will be performed at Screening, after signed informed consent has been obtained:

Inclusion and exclusion criteria will be assessed at Screening and recorded in the source 
documents and the eCRF.  

Pregnancy prevention counseling (refer to Section 6.1.1).

Medical (including surgical, COVID-19 vaccines, toxicities of prior treatments, known 
allergies) history, oncologic history, and demographic data (including each subject’s date of 
birth, sex, race, and ethnicity) will be collected during Screening as consistent with local 
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regulations (eg, if the full date of birth will not be collected but only month and year, age at 
screening will be collected). Oncologic history will include a detailed history of the primary 
diagnosis and date, therapies, and responses.  

Information on prior and concomitant medications and procedures will be collected (refer to 
Section 6.2.1).

Registration in the integrated response technology system (IRT).

Adverse event monitoring (refer to Section 10).

Height and weight measured.

Vital signs assessed (refer to Section 6.2.3).

Physical examination (source documented only) and ECOG PS (refer to Section 6.2.4).

RT-PCR testing for SARS-CoV-2 is mandatory within 7 days prior to first dose of CC-90009 
(C1D1). The RT-PCR test should be based on institutional or local guidelines. 

If a subject is identified to have SARS-CoV-2 infection during the screening period, subjects
may be considered eligible for the study after meeting all inclusion/exclusion criteria related 
to active infection, and after meeting the following criteria: 

At least 10 days (20 days for severe/critical illness) have passed since symptoms first 
appeared or positive RT-PCR or viral antigen test result, and 

at least 24 hours have passed since last fever without the use of fever-reducing medications, 
and 

acute symptoms (eg, cough, shortness of breath) have resolved, and 

in the opinion of the investigator, there are no COVID-19 sequelae that may place the 
participant at a higher risk of receiving investigational treatment.

In the instance of a SARS-CoV-2 infection during Screening, the Screening period may be 
extended beyond the 28-day timeframe with Sponsor Medical Monitor approval; Any 
Screening tests already performed which could potentially be affected by the SARS-CoV-
2 infection or its complications on an individual basis and agreed upon with the Sponsor 
Medical Monitor (eg, hematology and chemistry labs) should be repeated closer to C1D1.

A 12-lead ECG in triplicate (refer to Section 6.2.5) will be performed ≥72 hours prior to the 
first dose of CC-90009 with results received from the central read prior to dosing to fulfill the 
eligibility criteria.

Left Ventricular Ejection Fraction (LVEF) assessment (refer to Section 6.2.6).

Pregnancy β-subunit of human chorionic gonadotropin (β-hCG) test for FCBP as per PPP 
(refer to Appendix L and Section 6.2.7).

As per the PPP, FCBP must have two negative pregnancy tests (sensitivity of at least 25 
mIU/mL) prior to starting CC-90009.  The first pregnancy test must be performed within 
10-14 days prior to the start of CC-90009 and the second pregnancy test performed within 
24 hours prior to the start of CC-90009.  The results must be confirmed to be negative prior 
to dosing. 

Clinical laboratory tests [hematology, serum chemistry, glucose-6-phosphate dehydrogenase 
(G6PD), 25-hydroxyvitamin D level, PT, INR, PTT, and urinalysis; refer to Section 6.2.8] are 
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to be completed within the timeframe specified in Table 4, Table 6, Table 31, Table 33,
Table 35, and Table 37.

Both a free (ionized) serum calcium test and a corrected serum calcium test (corrected for 
albumin) should be obtained at Screening to establish baseline values; either may be used
to fulfill the inclusion criteria (refer to Section 4.2).

Creatinine clearance is determined at Screening.

Disease (efficacy) assessments (refer to Section 6.4) with the bone marrow aspiration and/or
biopsy are collected during Screening within 14 days (Day -14 through Day -1) prior to the 
first dose of CC-90009. Pharmacodynamic bone marrow biomarker samples are obtained at 
the same time (refer to Section 6.6.3).

In Part A, both bone marrow aspirate and biopsy are mandatory at all time points.

In Part B, both a bone marrow aspirate and biopsy should be performed at Screening. 
Thereafter, bone marrow aspirates are sufficient; a bone marrow biopsy can be collected 
in conjunction with an aspirate if it is standard institutional practice. A bone marrow biopsy 
must be collected if adequate aspirate sample is not attainable. 

In Part B, bone marrow aspirate and/or biopsy, peripheral blood smear, and relevant 
clinical documentation will be sent to a central lab for analysis and to confirm diagnosis 
and baseline disease characteristics. Details on timing and quantity of material required 
will be specified in the laboratory manual. All hematology and bone marrow pathology 
reports generated by central laboratories and used to establish subject’s eligibility will be 
sent for sponsor review ahead of cohort assignment (if timing allows based on clinical 
urgency) to provide  for any deficiencies in documentation to be addressed. 

In Part B, on a case-by-case basis and after consultation with the Medical Monitor, it will 
be determined if local pathology reports can be used to support R/R AML and R/R HR-
MDS subjects’ eligibility and cohort assignment. Please note that a bone marrow aspirate 
and/or biopsy sample is still required to be sent to the central laboratory prior to enrollment. 

Pharmacodynamic biomarker blood samples will be collected during Screening within 14 days 
(Day -14 through Day -1) prior to the first dose of CC-90009 (refer to Section 6.6.2). It is 
preferable to collect and process these samples on the same day that the bone marrow samples 
are obtained.

Eligible subjects will start calcium, calcitriol, and vitamin D supplementation at least 3 days 
prior to the first dose of CC-90009 in Cycle 1 (refer to Section 7.2). Subjects will be provided 
with a diary card to record the date and time they take the supplements.
6.1.1
Pregnancy Risk Counseling
The CC-90009 PPP for Celgene Clinical Trials (refer to Appendix L) applies to all subjects 
receiving CC-90009 therapy and will be given to sites as a separate document.
Qualified healthcare professionals will be trained by Celgene, or designee, in the requirements 
specific to contraceptive counseling of subjects.  Once trained these healthcare staff will counsel 
subjects prior to the administration of CC-90009 and at the beginning of each subsequent cycle to 
ensure that the subject has complied with all requirements including use of birth control and that 
the subject understands the risks associated with CC-90009.  This step will be documented with a 
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completed Education and Counseling Guidance Document, and CC-90009 will not be 
administered until this step occurs.
Per the PPP, the Investigator must confirm with the subject at each visit that their methods of birth 
control follow the PPP or confirm the subject’s commitment to complete abstinence.
A CC-90009 Information Sheet will be provided to each subject before the first dose of CC-90009.
6.2
Treatment Period
All subjects who fulfill the inclusion/exclusion criteria who are continuing in the study will be 
registered in the IRT system prior to receiving CC-90009 on Day 1 of Cycle 1.
All subjects will be required to start calcium, calcitriol, and vitamin D supplementation at least 
3 days prior to the first dose of CC-90009 in each cycle and continue until ≥3 days after the last 
dose of CC-90009 in each cycle (eg, ≥ Day 8 when CC-90009 is administered on Days 1-5, ≥ Day 
10 when CC-90009 is administered on Days 1-7, or ≥ Day 13 when CC-90009 is administered on 
Days 1-3/8-10 or Days 1-10).  Supplementation may be extended if hypocalcemia occurs (refer to 
Section 7.2.13.2). Subjects will document taking the supplements on diary cards that will be 
reviewed on Day 1 of each cycle and at the EOT visit. Subjects should be adequately hydrated (eg, 
2 to 3 liters of oral or IV fluids per day) starting the day prior to CC-90009 administration and 
continuing through each day of CC-90009 administration. Refer to Section 7.2 and Section 8.3
for detailed information.
6.2.1
Concomitant Medication and Procedures
All concomitant medications and procedures taken or conducted beginning when the subject signs 
the ICD, throughout the study, and until 28 days after the last dose of CC-90009 will be recorded 
in the source documents and eCRF.
6.2.2
Adverse Event Monitoring
Adverse events (AEs) and serious adverse events (SAEs) will be recorded from the time a subject 
signs the ICD until 28 days after the last dose of CC-90009.  
Subjects experiencing AEs will be monitored with relevant clinical assessments and laboratory 
tests, as determined by the Investigator (refer to Section 10 for detailed information).  Every 
attempt will be made to document resolution dates for ongoing AEs.  The AEs will be recorded on 
the AE page of the eCRF and in the subject’s source documents.  
6.2.3
Vital Signs and Weight 
Vital signs include body temperature, blood pressure, pulse rate, and respiration rate and will be 
recorded at Screening and during the study at various time points for safety monitoring as 
described in Table 4 – Table 7, Events in Appendix K and Appendices M-O.
In Cycle 1 and for subjects who are administered as in-patient in Cycles ≥ 2, on days that CC-90009 
is administered, vital signs will be obtained prior to dosing (≤3 hours), and at 60 minutes (± 15 
minutes) and 6 hours (± 1 hr) after the end of the administration of the dose. Starting in Cycle 2 in 
the outpatient setting, vital signs will be obtained prior to dosing (≤3 hours) and at 60 minutes (± 
15 minutes) after the end of the administration of the dose. Additional vital signs should be 
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obtained as clinically indicated per the Investigator’s medical assessment. Recorded measurements 
will be captured in the source document and eCRF.  The subject’s weight will be recorded in the 
source document and eCRF at the visits listed in Table 4 – Table 7, Events in Appendix K and
Appendices M-O.
6.2.4
Physical Examination and ECOG Performance Status
Complete physical examination and ECOG PS (refer to Appendix C) will be performed at the 
visits listed in Table 4 – Table 7, Appendix K, and Appendices M-O. Results for both will be 
recorded in the source document.  Results for the ECOG PS will also be collected on the eCRF. 
Physical examination findings will be classified as either normal or abnormal.  If abnormal, a 
description of the abnormality and clinical importance will be provided in the source documents.  
Clinically significant changes from baseline will be recorded in the AE section of the eCRF.  
6.2.5
12-Lead Electrocardiograms
Triplicate standard 12-lead ECGs will be recorded at the visits listed in Table 4 –Table 7,
Appendix K, and Appendices M-O.  The 12-lead ECGs (12-lead at 25 mm/sec reporting rhythm, 
ventricular rate, PR interval, QRS complex, QT interval, and QTc interval) will be performed after 
the subject has been in the supine position for at least 5 minutes.  If the scheduled time for an ECG 
coincides with a PK blood collection, the blood draw should be performed as scheduled, with the 
ECG being performed prior to the blood collection.
Triplicate ECGs (3 recordings within 2 ± 1 minute intervals) will be performed at:

Screening (≥72 hours prior to Day 1 with results received from the central ECG laboratory 
prior to the first dose of CC-90009)

Cycle 1, Day 1

Predose (≤ 60 minutes prior), 

Post-end of infusion (EOI) at 30 minutes (± 5 minutes), 2 hours, 4 hours, and 8 hours (each 
± 30 minutes) [timings are given in reference to the end of the infusion]

Cycle 1, Day 5 (D1-5 schedule only) or Cycle 1 Day 7 (D1-7 schedule only)

If C1D5 or C1D7 is a dosing day, predose (≤ 60 minutes prior) and 30 minutes (± 5 
minutes) after the EOI

If C1D5 or C1D7 is not a dosing day (eg, D1-3/D8-10 schedule), no ECG done

If enrolled on the D1-10 schedule, no ECG done on C1D5 or C1D7

Cycle 1, Day 8 (C1D8)

If C1D8 is a dosing day, predose (≤ 60 minutes prior) and 30 minutes (± 5 minutes) after 
the EOI

If C1D8 is not a dosing day, single time point

Cycle 1, Day 10 (C1D10)

If C1D10 is a dosing day, predose (≤ 60 minutes prior) and 30 minutes (± 5 minutes) after 
the EOI

If C1D10 is not a dosing day (eg, D1-5 or D1-7 schedules), no ECG done
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
Cycles ≥ 2, Day 1

predose (≤ 60 minutes prior)
A single ECG will be performed at the EOT visit. 
During the Treatment Period, Investigators will make immediate clinical decisions based on their 
interpretation of the ECG results and provide their overall assessment of the ECG in the eCRF. 
Clinically significant changes from baseline will be recorded in the AE section of the eCRF.  
The ECG outputs will also be uploaded to the central ECG laboratory for definitive analysis and 
interpretation.  
6.2.6
Left Ventricular Ejection Fraction
Left ventricular ejection fraction (LVEF) will be assessed by MUGA scan or ECHO at Screening 
in all subjects (not required if an assessment has been performed within 28 days prior to the start 
of study treatment).  Follow-up assessments are required as indicated in Table 5, Table 7, Table 32,
Table 34, Table 36, or Table 38. Follow-up assessments should use the same procedure used at the 
screening assessment.  A clinically significant reduction is defined as either a ≥ 20% absolute 
reduction in LVEF or drop to below 45%.
6.2.7
Pregnancy Testing
A FCBP is defined as a female who:  1) has achieved menarche at some point, 2) has not undergone 
a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal 
(amenorrhea following cancer therapy does not rule out childbearing potential) for at least 
24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months).  
The Investigator will classify a female subject as a FCBP according to this definition.  Pregnancy 
testing is not required for non-FCBP subjects but justification must be recorded in the eCRF and 
the source document.  Pregnancy testing will be conducted by the local laboratory.
For a FCBP, pregnancy testing will be conducted at the visits listed in Table 4 – Table 7, Appendix 
K, or Appendices M-O as outlined in the PPP (refer to Appendix L).
Results for pregnancy tests will be recorded in the source document and eCRF.  
6.2.8
Clinical Laboratory Tests
The following laboratory assessments will be performed at the Screening visit and during the study 
at the time points as described in Table 4 – Table 7, Appendix K, and Appendices M-O.  All 
samples on dosing days should be drawn predose (≤ 5 hours prior) unless otherwise specified.  
Laboratory assessments will be recorded in the source document and eCRF and are the following: 

Hematology:  CBC including hemoglobin, hematocrit, red blood cell count with indices, WBC 
count with absolute differential (including blast count) and platelet count.

Serum chemistry:  albumin, total protein, bicarbonate or carbon dioxide (CO2), corrected 
calcium (corrected for albumin), C-reactive protein (CRP), ferritin, magnesium, phosphorus, 
creatinine, urea/blood urea nitrogen (BUN), glucose (fasting ≥ 4 hours), potassium, sodium, 
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chloride, total bilirubin (fractionate if outside normal range), alkaline phosphatase, AST 
(SGOT), ALT (SGPT), LDH, and uric acid.

Additional monitoring for TLS (bicarbonate or CO2, phosphorous, creatinine, urea/BUN, 
potassium, sodium, chloride, LDH, and uric acid) performed in Cycle 1 on Days 1, 2, and 
3 at 12 hours (± 1 hour) postdose.

Additional serum Ca (corrected for albumin) and Mg tests performed in Cycle 1 on dosing 
days at 6 and 12 hours (± 1 hour) postdose and in Cycles ≥2 prior to dosing. For subjects 
experiencing Grade ≥ 2 hypocalcemia in Cycle 1, additional serum Ca (corrected for 
albumin) and Mg tests will be performed all dosing days at 6 and 12 hours (± 1 hour) 
postdose in Cycles ≥2. Additional serum PTH tests performed in Cycle 1 on dosing days 
at 6 hours (± 1 hour) postdose.  
NOTE:  In the event of Grade ≥ 2 hypocalcemia and abnormal levels of serum albumin, a 
serum ionized calcium test and more frequent calcium monitoring must be performed (refer 
to Section 7.2.13.2). Hypocalcemia adverse event grading should be reported as the 
highest grade determined.

G6PD at Screening only

Special calcium metabolism monitoring tests:

serum PTH, total P1NP, and serum β-CTx

urine calcium/creatinine ratio obtained from spot (random) urine collection

Serum 25-hydroxyvitamin D level 

Special chemistry:  amylase, lipase, T-cell subsets (cluster of differentiation [CD]4+ and 
CD8+), thyroid-stimulating hormone (TSH; if abnormal reflex to free thyroxine)

Coagulation:  PT, INR, and PTT at Screening and only repeated during the study for subjects 
on anticoagulation therapy as shown in Table 5, Table 7, Table 32, Table 34, Table 36, or
Table 38 and as clinically indicated.

Urinalysis: dipstick

microscopy in the event of a positive (1+ or greater) blood or protein

24-hour collection for creatinine clearance and protein quantification in the event of 2+ or 
greater protein

Creatinine clearance determination required at Screening to fulfill inclusion criteria (refer to 
Section 4.3).
6.2.9
End of Treatment 
An EOT evaluation (refer to Table 5, Table 7, Table 32, Table 34, Table 36, or Table 38 for 
procedures) will be performed for subjects who are withdrawn from treatment for any reason as 
soon as possible (≤28 days) after the decision to permanently discontinue treatment has been 
made. For subjects who complete dosing in Cycle 4, this visit should be completed on Day 28 (± 2 
days) of Cycle 4.
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6.3
Follow-up Period
6.3.1
Safety Follow-up
All subjects will be followed for 28 days after the last dose of CC-90009 for AE reporting and 
concomitant medication information. The 28-day (± 3 days) safety follow-up contact may be by 
telephone. In addition, any SAEs made known to the Investigator at any time thereafter that are 
suspected of being related to CC-90009 will be reported as described in Section 10.1. Subjects will 
be followed for all SAEs and all AEs (SAEs and non-serious AEs) associated with confirmed or 
suspected SARS-CoV-2 infection until resolution, the condition stabilizes, the event is otherwise 
explained, the event is deemed irreversible, the subject is lost to follow-up, or for suspected cases, 
until SARS-CoV-2 infection is ruled-out.  
Pregnancy testing will be performed per the PPP and Table 5, Table 7, Table 32, Table 34, 
Table 36, or Table 38.
6.3.2
Efficacy Long Term Follow-up
Subjects without documented progression of disease (or relapse) or start of new anti-cancer 
therapies will have efficacy evaluations of complete blood counts and peripheral blood smears
performed every subsequent 8 weeks (± 1 week) for the 1st year and every 12 weeks (± 2 weeks) 
for the 2nd year or until progression of disease (or relapse), initiation of a new anticancer therapy, 
withdrawal from the study, death, or the End of Trial, whichever comes first. A bone marrow 
evaluation will be completed at the end of the 1st year and as clinically indicated during the Follow-
up Period.
Information (including dates) on new anticancer therapies initiated will be collected until 
progression of disease (or relapse), withdrawal from the study, death, or the End of Trial, 
whichever comes first.
Information will also be collected on any study drug-related SAEs.  
6.3.3
Survival Follow-up
After the Safety Follow-up visit, all subjects will be followed according to the schedule for the 
efficacy long term follow-up (refer to Section 6.3.2) for survival for up to 2 years or until death, 
lost to follow-up, or the End of Trial, whichever occurs first. Survival follow-up may be conducted 
by record review (including public records) and/or telephone contact with the subject, family, or 
the subject’s treating physician.
6.4
Efficacy Assessment 
Disease assessments by bone marrow aspiration and biopsy, along with complete blood counts and 
examination of peripheral blood smears will be performed as indicated in Table 4 – Table 7, 
Appendix K, or Appendices M-O.
In addition, bone marrow aspirates and biopsies must be 
collected in order to confirm CR or morphologic CR with incomplete blood recovery (CRi) and
morphologic CR with partial hematologic recovery (CRh), relapse after CR, CRi, or CRh (as 
assessed by the Investigator based on CBC with WBC differential results), or disease progression.  
If disease progression features are observed following the bone marrow evaluation, a repeat bone 
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marrow evaluation should be performed one month later to confirm disease progression (as 
described below).  Additional aspirates and/or biopsies will be collected as clinically indicated (eg, 
Cycle 1 Day 15, based on Investigator’s medical assessment).  
Progressive disease will be defined as:

A > 50% increase in bone marrow blast count percentage from the baseline (screening) bone 
marrow blast count that persists for at least 2 bone marrow assessments separated by at least 1 
month, unless the baseline bone marrow blast count is > 70%, in which case, a finding of > 
70% blasts that persists for 2 post baseline bone marrow assessments separated by at least 1 
month would be considered progression, or

A doubling of the baseline absolute peripheral blood blast count that persists for ≥7 days and 
the final absolute peripheral blood blast count is > 10 x 109/L.
The date of progressive disease is defined as the first date that there was either a > 50% increase 
in bone marrow blast count from baseline, a persistence of bone marrow blasts > 70% in subject 
with a baseline bone marrow blast count of > 70%, or a doubling of the peripheral blood blast 
count.
Treatment failure will be defined as progressive disease or not achieving at least partial remission 
(PR) by the end of the treatment period. In the absence of progressive disease (as defined above) 
or unacceptable toxicity, subjects may continue treatment with CC-90009 through Cycle 4 if they 
are deriving benefit, as judged by the Investigator. Failure to achieve a response and not meeting 
the criteria for progressive disease will be considered stable disease. Additional cycles of treatment 
beyond Cycle 4 may be allowed after discussion with the Medical Monitor if the subject is 
demonstrating clinical benefit (stable disease or PR or CR) and if tolerating the study drug without 
unacceptable toxicity.
Bone marrow aspirates and biopsies are to be evaluated for morphology, flow cytometry, 
karyotype, and molecular studies (eg, FLT3, KIT, NPM1, CEBPα mutational status if positive on 
previous bone marrow biopsies). In Part B, bone marrow analyses will be performed at a central 
laboratory. Molecular and cytogenetic studies may be omitted at the:

Screening bone marrow evaluation, if they were completed within the prior 90 days and the 
results are available to enter on the eCRFs,

Part A, Cycle 1 Day 42 ± 3 days (or at time of hematologic recovery) bone marrow evaluation
for subjects with extended safety monitoring in Cycle 1 if a complete response is documented 
on Day 28.
The marrow aspiration and core sampling (biopsy) should be performed according to the standard 
of care and analyzed at the local site’s laboratory in accordance with the International Council for 
Standardization in Hematology (ICSH) Guidelines (Lee, 2008).  
The clinical activity of CC-90009 will be evaluated by the Investigator by assessing response to 
treatment according to the IWG Response Criteria in AML (Cheson, 2003; refer to Appendix C). 
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Treatment decisions will be based on Investigator’s assessment. MDS response will be based on 
the IWG Response Criteria for Myelodysplasia (Cheson, 2006; refer to Appendix G).
Subjects who discontinue treatment for reasons other than disease progression (or relapse), start of 
a new anticancer therapy, or withdrawal of consent from the entire study will have disease 
assessments performed up to a maximum of 2 years according to the specified assessment schedule 
(refer to Section 6.3.2) until progression and/or initiation of new systemic anticancer therapies.
6.5
Pharmacokinetics 
6.5.1
Blood Collection for PK Analysis
In Part A, intensive blood samples will be collected from all subjects for evaluation of PK of 
CC-90009 in plasma at time points specified in Table 40, Table 41, Table 42, or Table 43. In 
Part B, intensive blood samples will be collected from approximately 10 selected subjects in each 
cohort for evaluation of PK of both CC-90009 and hydroxypropyl-β-cyclodextrin in plasma; sparse 
blood samples will be collected from the remaining subjects for evaluation of PK of CC-90009.  
Time points are specified for intensive and sparse PK sampling, respectively in Table 44 or 
Table 8.
The concentration of R- and S-enantiomers of CC-90009, ie CC0782618 (R-enantiomer) and
CC0782619 (S-enantiomer), in plasma will be determined by LC/MS. The CC-90009 
concentration will be calculated as a sum of its R- and S-enantiomers. An exploratory analysis of 
CC-90009 metabolites in plasma may be performed utilizing the blood samples collected for PK 
evaluation.
The blood PK samples at 2, 15, and 30 minutes after the EOI MUST be collected from the arm 
contralateral to the arm used for CC-90009 administration.  If a peripheral IV catheter is used for 
the CC-90009 IV administration, the PK samples should be obtained from the opposite arm. In 
general, blood for PK samples should not be drawn from a central line. If a peripheral line is not 
accessible, blood for PK samples drawn from a central line MUST be collected after the lumen is 
flushed with saline, and the non-dosing lumen of a dual/triple lumen catheter should be used. 
Administration and PK blood draw locations will be recorded in the database.
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Table 8:
Blood Pharmacokinetic Sampling Schedule in Part B: 2.4 and 3.0 
mg Days 1-7 Schedule
Time Relative to CC-90009 
Administration
Collection Window
Intensive
Sparse
Cycle 1 Day 1 and Cycle 1 Last Dose
0
≤ 30 minutes prior to start
X
Mid-infusion (eg, at 15 minutes in a 
30 minute infusion)a
± 1 minute
X
15 minutes after EOI
± 5 minutes
X
30 minutes after EOI
± 5 minutes
X
X
1 hour after EOI
± 5 minutes
X
X
2 hours after EOI
± 10 minutes
X
4 hours after EOI
± 10 minutes
X
X
8 hours after EOI
± 30 minutes
X
12 hours after EOI
± 2 hours
X
24 hours after EOI
± 3 hours
Xb
Xb
Cycles 2-4
Second to last dosing day, pre-dose
≤ 30 minutes prior to start
X
X
Last dosing day, pre-dose
≤ 30 minutes prior to start
X
X
Abbreviation: EOI = end of infusion/injection. 
a In cases where the only access for drug administration is the central line, mid-infusion PK draws may be omitted.
b 24 hours after EOI on day 1 occurs on Day 2. Must be drawn prior to the administration of CC-90009 on Day 2.
The following information must be captured in the eCRFs:

The dose level and total dose administered.

The actual clock time of the start of the CC-90009 IV administration.

The actual clock time of the EOI.

The actual clock time of each PK sample collection.

The location of drug administration and PK sample collection.
The Sponsor may conduct additional analyses on the PK samples in order to follow-up the safety 
of the study treatment or to better understand the progression of the disease or the disease’s 
response to the study treatment.  
See the Laboratory Manual for sample collection, handling, and processing instructions.
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6.5.2
Urine Collection for PK Analysis
Urine will be collected in approximately 10 evaluable subjects in Part A and/or Part B.  Collection 
will occur on Cycle 1 Day 1. Urine will be collected predose (within approximately 60 minutes 
prior to dosing; spot collection to serve as the blank control) and then pooled as a single block over 
the intervals of 0 to 4, 4 to 8, 8 to 12, and 12 to 24 hours postdose.  Within approximately 15 
minutes of ending each collection interval, subjects should empty their bladder prior to the start of 
each new collection interval.  This urine should be added to the pooled urine for the current 
collection interval.  During each collection interval, all urine voided must be collected (ie, no urine 
should be allowed to pass into the toilet).  Incomplete collection or missed samples will be recorded 
as a deviation.  
The concentration of CC-90009 and hydroxypropyl--cyclodextrin in urine will be determined. 
An exploratory analysis of CC-90009 metabolites in urine may be performed utilizing the urine 
samples collected for PK evaluation.
The following information must be captured in the eCRFs:

The dose level and total dose administered.

The actual clock time of the start and end of the CC-90009 IV administration.

The actual clock time of the start and end of each urine collection interval.

The weight of urine collected during each collection interval (eg, 200 g during the 0 to 4 hours 
postdose collection interval). 
See the Laboratory Manual for sample collection, handling, and processing instructions.
6.6
Biomarkers, Pharmacodynamics, Pharmacogenomics 
6.6.1
Pharmacogenomics Sample
A sample (eg, buccal swab or nail clippings) will be collected prior to dosing on Cycle 1 Day 1
for assessment of potential pharmacogenomics markers of CC-90009 safety, activity or exposure.  
6.6.2
Pharmacodynamic Biomarker Blood Samples
The schedules for blood collections for pharmacodynamic biomarkers are provided in Table 9 and 
Table 10.
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Table 9:
Sample Collection of Blood for Pharmacodynamic Biomarkers on D1-5 
Schedule and Alternative Schedules with up to 10 consecutive dosing 
days (eg, D1-7 and D1-10) for Part A or Part B
Screeni
ng
Cycle 1a
Day 1
Day 2
Day 3
Day 4
Last 
Day of 
Dosing
Day 
8b
Day 
15
Day 
28d
Sample
Day -
14 
to -1c
Pred
ose 
(≤ 3 
hrs)
6 hours  
(± 15 
min) 
after 
EOI
Predose 
(≤ 3 hrs)
6 hours 
(± 15 
min) 
after 
EOI
Predose 
(≤ 3 hrs)
6 hours 
(± 15 
min) 
after 
EOI
Predose 
(≤ 3 hrs)
6 hours  
(± 2 hr) 
after 
EOI
AM
AM
AM
Whole blood, flow 
cytometrya
X
X
X
Xg
Xg
X
X
X
Xg
X
Whole blood, PD 
biomarkers
Xd
Xd,e
Xd,e
Blood for PBMC, 
PD protein & 
RNAa
X
X
Xg
X
X
Blood for PBMCs, 
ex vivo sensitivity 
assays, 
phenotyping & 
sequencing
X
Blood for plasma, 
cytokine assays
X
X
X
X
X
X
SARS-CoV-2 
Serologyf
X
Abbreviations:  AM = morning; EOI = end of infusion/injection; PBMC = peripheral blood mononuclear cells; PD = 
pharmacodynamic; RNA = ribonucleic acid; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.
a If intra-subject dose escalation occurs, blood samples for PD assays will also be collected during the first cycle at the increased 
dose on Days 1, 2, 3, 4, 8 and 15; see laboratory manual for details.
b If Day 8 is a dosing day due to use of an alternate schedule per the SRC, obtain samples pre-dose.
c Obtaining the Screening samples on the same day as the Screening bone marrow aspirate and biopsy is preferred.
d For subjects in Part B only. Last day of dosing is defined as the last consecutive planned day (eg, Day 5 on the Days 1-5 schedule
or Day 7 of the Days 1-7 schedule). See also footnote e and Section 6.6.3 for allowable days for the Cycle 1 Last Day of Dosing 
sample collection (ie, on Days 1-5 schedule, Day 4 or 5; on Days 1-7 schedule, Day 6, 7, or 8). 
e Collected the same day the bone marrow samples are collected for PD or response assessments in Cycles 1, 2 and 4
f
Serum collected to be used for possible measurements of anti-SARS-CoV-2 serology (anti-SARS-CoV-2 total or IgG (see 
Table 6)
g For Part A only.
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Table 10:
Sample Collection of Blood for Pharmacodynamic Biomarkers using 
the Alternate D1-3/D8-10 Schedule for Part A or Part B
Screening
Cycle 1
Day 1
Day 2
Day 3
Day 4
Day 8
Day 9
Day 
15
Day 
22
Sample
Day -14 
to -1a
Predose 
(≤ 3 hrs)
6 hours 
(± 15 min) 
after EOI
Predose (≤ 
3 hrs)
Predose 
(≤ 3 hrs)
AM
Predose 
(≤ 3 hrs)
Predose 
(≤ 3 hrs)
AM
AM
Whole blood, 
flow cytometrya
X
X
X
X
X
X
X
X
X
Blood for 
PBMC, PD 
protein & RNAa
X
X
X
X
X
X
Blood for 
PBMCs, ex vivo 
sensitivity 
assays, 
phenotyping & 
sequencing
X
Blood for 
plasma, cytokine 
assays
X
X
X
X
X
X
X
X
Abbreviations:  EOI = end of infusion/injection; PD = pharmacodynamic; RNA = ribonucleic acid.
a Obtaining the Screening samples on the same day as the Screening bone marrow aspirate and biopsy is preferred.  
6.6.3
Pharmacodynamic Biomarker Bone Marrow Samples
Bone marrow aspirates and biopsy for PD and prognostic/predictive biomarkers will be collected 
at the time points indicated in Table 4 – Table 7, Appendix K, or Appendices M-O. Exploratory 
tests may be performed to determine Minimal Residual Disease (MRD) status at efficacy time
points. In Cycle 1 on Day 5 on the D1-5 dosing schedule, the PD samples will be collected between 
4 to 8 hours after CC-90009 is administered. If necessary due to scheduling conflicts, the PD 
samples may be collected on Day 4 (4 to 8 hours after dosing). If the dosing interval (schedule) is 
extended, then samples will be obtained on the last day ± 1 day (ie, if extended to consecutive 7 
days or 10 days, the PD bone marrow sample can be collected on Day 6-8 [Appendix M] or 9-11 
[Appendix O]). For the D1-3/D8-10 schedule, the PD bone marrow sample is collected on Day 9 
or 10 (Appendix K).
Additionally, bone marrow aspirates and/or biopsies may be obtained in both Part A and Part B, 
after a CR is confirmed, if relapse is suspected, or following treatment discontinuation to elucidate 
effects of long-term treatment or resistance mechanisms, or as clinically indicated based on the 
Investigator’s medical assessment. When obtained for any of the reasons above, samples for 
biomarker assessments will also be collected at the same time.
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6.6.4
SARS-CoV-2 Serology Samples
Serum and plasma samples may be assessed by enzyme-linked immunosorbent assay, seromics, 
ctDNA measurements, metabolomics, and/or other relevant multiplex-based protein assay 
methods for immune-related factors that may be associated with efficacy or AEs; such factors may 
include, but are not limited to, assessments of cytokines, chemokines, inflammatory factors, 
SARS-CoV-2 serologic status, and ctDNA. Serum will be collected predose on Cycle 1 Day 1 (or 
at screening), approximately every 6 months during study treatment and at EOT to be used for
possible measurements of anti-SARS-CoV-2 serology (anti-SARS-CoV-2 total or IgG). Serum 
should also be collected approximately 4 weeks after documented or suspected SARS-CoV-2 
infection (see Table 6 – Table 7 and Table 35 – Table 36). 
6.6.5
All Pharmacodynamic and Pharmacogenomics Samples 
Refer to the Laboratory Manual for sample collection, handling, and processing instructions.  
The Sponsor may conduct additional analyses on the biomarker samples in order to follow up the 
safety of the study treatment or to better understand the progression of the disease or the disease’s 
response to the study treatment or the subject’s predisposition to therapeutic response to CC-
90009. 
6.7
Additional and Optional Research
Additional and optional research as described below may be performed using left-over samples 
originally collected for another test required in this study or using samples collected specifically 
for biomarker testing. The research may involve genetic tests using DNA or RNA and may lead to 
the development of new diagnostic tests.
6.7.1
Additional Research
Additional research related to the study drug and/or disease may be performed. The results of this 
additional research could help to improve the diagnosis and/or the treatment of this disease in the 
future. 
6.7.2
Optional Research
Optional research not related to the study drug or the subject’s disease may be performed. The 
subject’s decision to participate in this optional research will not impact their ability to participate 
in the main study.
6.8
Subject Reported Outcomes
Not Applicable
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7
DESCRIPTION OF STUDY TREATMENT
7.1
Description of Investigational Product
7.1.1
Physical Properties
CC-90009 has a molecular weight of 461.85 g/mole. It is a white to off-white powder. 
7.1.2
Formulation
Celgene Corporation will supply CC-90009 clinical drug product as a lyophilized powder for 
reconstitution to solution in single-use vials and it should be stored per the product label. The drug 
product is available in two different formulations: Gen 1 and Gen 2b. The study will initially 
employ Gen 1 (DL1: 0.3 mg, DL2: 0.6 mg, and DL3: 1.2 mg), and then during dose escalation, 
Gen 2b was introduced at DL4 (2.4 mg) to replace the Gen 1 formulation. Each vial of Gen 1 CC-
90009 contains 1.05 mg of CC-90009, 18.6 mg anhydrous citric acid, 18.5 mg anhydrous sodium 
citrate, and 252.0 mg of Kleptose™hydroxypropyl beta-cyclodextrin (HPBCD) as a freeze dried 
powder.  CC-90009 is slightly hygroscopic. Each vial of Gen 2b formulation of CC-90009 contains 
1 mg CC-90009 and 800 mg hydroxypropyl-beta-cyclodextrin (HPBCD) as a freeze dried powder. 
CC-90009 clinical drug product is packaged in a 20 mL US Pharmacopeia (USP) Type I glass vial 
or local equivalent. The CC-90009 vial does not contain any preservative and is for single use 
only. CC-90009 should be prepared according to the package instructions, the CC-90009 
Pharmacy Manuals, and local practice regulations. Gen 1 formulation is reconstituted in sterile 
Water for Injection (SWFI). Gen 2b formulation is reconstituted in 0.45% sodium chloride (half 
strength normal saline) and further diluted in 0.9% sodium chloride (normal saline) for injection
(eg, for infusion doses between 0.6 and 10 mg, Gen2b formation is reconstituted with 4.5 mL of 
0.45% sodium chloride [half strength normal saline] to a concentration of 0.2 mg/mL The 
reconstituted solution can be further diluted in 0.9% sodium chloride [normal saline] to achieve a 
50 mL volume.)
DMA is a process solvent used during manufacture of Gen 1 formulation of CC-90009 that is 
removed during processing. The daily dose of DMA residual solvent in Gen 1 CC-90009 must not 
exceed the ICH permitted daily exposure limit (10.9 mg/day) to proceed with dose escalation
above a CC-90009 daily dose of 2.4 mg. Gen 2b CC-90009 was developed to enable doses above 
the limits imposed on Gen 1 formulation. Gen 2b CC-90009 is permitted at doses up to 20 mg CC-
90009 per day. The SRC determined the dose cohort for introduction of Gen 2b CC-90009 during 
Part A of the study to be DL4: 2.4 mg on Days 1-5.
Females of childbearing potential and fertile males should not handle or administer CC-90009 
unless they are wearing gloves.
7.2
Treatment Administration and Schedule
CC-90009 will be administered QD on Days 1 to 5 (on the D1-5 dosing schedule) of Cycles 1 to 
4. Subjects will be closely monitored throughout the administration of CC-90009 and for 1 hour 
following each administration.  In addition, subjects will be admitted as inpatients for each 
administration of CC-90009 and monitoring in Cycle 1. For Cycles ≥ 2, subjects will either be 
admitted as inpatients or treated/monitored in a LSU per Investigator’s discretion. Subjects with 
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Grade ≥ 2 hypocalcemia in any cycle should be treated as inpatients in subsequent cycles (an 
exception can be made for subjects with grade 2 hypocalcemia lasting less than 24 hours that 
recovers without IV calcium [eg, calcium gluconate or calcium chloride] after discussion with the 
Celgene medical monitor). The SRC may evaluate modified dosing schedules (eg, increasing from 
5 to up to 10 consecutive days of dosing, intermittent schedules or longer infusion times) in 
additional cohorts, if necessary, based on toxicity, PK profiles, and PD findings. 
For CC-90009 doses at or above 3.6 mg, all subjects will receive a dose of steroids (eg,
dexamethasone 10 mg IV (or by mouth [PO] or equivalent) 30 min to 3 hrs prior to each daily dose 
of CC-90009 (Table 4 –Table 7, Appendix K, or Appendices M-O). For CC-90009 dosed at 3.0 
mg on the Days 1-7 and Days 1-10 dosing schedules, steroid premedication is recommended for 
each of the dosing days. On these schedules with longer dosing days, a lower dose of 
dexamethasone may be given (minimum of 4 mg) per Investigator’s judgement based on the 
subject’s expected tolerability of corticosteroids. The frequency and/or the dose of dexamethasone 
(or equivalent) administration may be modified based on evaluation and recommendation by the 
SRC (eg, D1-5, D1-7, D1-10, or D1, D3, D5).
All subjects will be required to start calcium, calcitriol, and vitamin D supplementation at least 
3 days prior to the first dose of CC-90009 in each cycle and continue until ≥ 3 days after the last 
dose of CC-90009 in each cycle (eg, ≥ Day 8 when CC-90009 is administered on Days 1-5, ≥Day 
10 when CC-90009 is administered on Days 1-7, or ≥ Day 13 when CC-90009 is administered on 
Days 1-3/8-10 or Days 1-10).  Supplementation may be extended if hypocalcemia occurs (refer to 
Section 7.2.13.2). The time and date of administration will be recorded on a diary card.
The calcium/calcitriol/vitamin D supplementation regimen is:

Calcium carbonate 500 mg elemental calcium PO 3 times a day (TID) (taken after meals to 
increase absorption)

Alternative preparations of calcium can be substituted but they must equal at least 1200 
mg of elemental calcium per day given in divided doses (eg, TID).

If the subject is on a proton pump inhibitor (PPI) or has gastric achlorhydria, then 
administer calcium citrate 630 mg elemental calcium PO TID 

Calcitriol 0.25 micrograms PO QD

Vitamin D supplementation is based on the Screening serum 25-hydroxyvitamin D level:

Level < 12 ng/mL – excluded from the study

Level 12 – 20 ng/mL – Vitamin D3 or D2 50,000 IU weekly

Level > 20 ng/mL– Vitamin D3 or D2 1000 IU QD
The risk of TLS with CC-90009 is unknown.  Subjects should be adequately hydrated (eg, 2 to 
3 liters of oral or IV fluids per day) starting the day prior to CC-90009 administration and 
continuing through each day of CC-90009 administration.  Medications to prevent or treat TLS 
are permitted (refer to Section 8.1).  
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In the absence of progressive disease (as defined in Section 6.4) or unacceptable toxicity, subjects 
may continue treatment with CC-90009 for a maximum of 4 cycles if they are deriving benefit, as 
judged by the Investigator.  
7.2.1
CC-90009 Preparation and Administration
Prior to administration, CC-90009 must be reconstituted using aseptic technique.  The 
reconstituted solution for IV administration may be stored at 5°C for up to 8 hours or room 
temperature for up to 4 hours. Total storage time of final diluted product in syringe or IV bag 
should not exceed 4 hours at room temperature (20-25ºC). Administration must be completed 
within the allowed storage time after reconstitution. If you store CC-90009, source documentation 
must be kept to demonstrate correct temperature was maintained during the storage period and the 
storage time after reconstitution was within the protocol limits.
Gen 1 CC-90009 is administered as an IV push (≤ 1 minute). Gen 2b CC-90009 should be
administered as an IV infusion (eg, 30 ± 5 minutes). The SRC may recommended alternate 
administration guidelines based on review of available clinical and laboratory safety data, PK 
profiles, and PD findings. Refer to the CC-90009 Pharmacy Manuals for detailed information on 
the preparation and administration of CC-90009. The start time, stop time, and infusion rate (if 
applicable) of each CC-90009 administration will be recorded in the source documents and on the 
eCRF.
7.2.2
Dose Escalation Criteria
Cohorts of one or more subjects each will be given CC-90009 at doses that will increase in 100% 
increments per cohort until ≥ 2 subjects experience a CC-90009-related Grade ≥2 adverse event 
(may be different cohorts) in the DLT window, or ≥ 1 subject experiences a DLT within the DLT 
window. At that time the current cohort and all subsequent cohorts will be expanded enrolling 3 
to 6 subjects (mandatory increase to 6 subjects if a DLT occurs). A dose escalation schedule with 
dose increments not to exceed 50% will concurrently be initiated in order to establish the NTD 
and MTD.  The number of cohorts depends on incidence of DLT.  A subject may experience more 
than one DLT.  Dose escalation decisions are based on the number of subjects experiencing DLT 
events.  The initial dose will be 0.3 mg. 
Dose escalation decisions will be made at the discretion of the SRC. The SRC may decide to 
evaluate a higher dose cohort, additional subjects within a dose cohort, intermediate dose cohorts, 
smaller dose increments, alternate dosing schedules (eg, increasing from 5 to up to 10 consecutive 
days of CC-90009 administration), and/or declare an MTD based on their review of available 
clinical and laboratory safety data, PK profiles, and PD findings. 
In the event that an alternate dosing schedule is evaluated, the starting dose and schedule will not 
exceed the dose intensity of a dose cohort that has previously met the criteria for dose escalation
(Figure 3). Refer to Section 3.1. 
Dose reduction and temporary delay of CC-90009 dosing due to toxicity is allowed, but dose 
reduction during Cycle 1 will constitute DLT.  
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7.2.3
Definition of a Subject Evaluable for DLT
All subjects who receive at least one dose of CC-90009 will be evaluable for safety.
After the first dose is administered in any cohort of subjects during dose escalation, subjects in 
each cohort are observed for at least 28 days and up to 42 days (Cycle 1, DLT window) before the 
next higher, protocol-specified dose cohort can begin.  A subject evaluable for DLT is defined as 
one that: 

Has received at least 80% of the total planned Cycle 1 dose (eg, ≥ 4 CC-90009 doses for the 
Days 1-5 schedule to be completed on or before Day 10, ≥ 6 CC-90009 doses for the Days 1-
7 schedule to be completed on or before Day 10, ≥8 doses by Day 14 for the Days 1-10 
schedule, or ≥ 5 doses by Day 14 for the D1-3/D8-10 schedule) of CC-90009 during Cycle 1 
without experiencing a DLT,
Or

Experienced a DLT after receiving at least one dose (or fraction thereof) of CC-90009.  
In the event that an alternate dose schedule (eg, increasing from 5 days to up to 10 consecutive 
days of dosing) is evaluated in Part A, the same criteria for determining DLT-evaluable subjects 
will be applied. Subjects who are non-evaluable for DLT will be replaced. Additional subjects 
within any dose cohort may be enrolled at the discretion of the SRC. In the event a subject is re-
enrolled/re-treated upon relapse (Section 3.1), the subject would only be considered DLT 
evaluable during the first cycle of their initial enrollment in Part A.  
7.2.4
Definition of Non-Tolerated Dose 
The NTD is defined as a dose level at which 2 or more of up to 6 evaluable subjects in any dose 
cohort experience a DLT in Cycle 1 during dose escalation.
If 2 or more of up to 6 subjects experience a DLT in the first dose cohort, a lower dose cohort may 
be explored at the discretion of the SRC (ie, 0.1 mg CC-90009).  
7.2.5
Definition of Maximum Tolerated Dose 
The MTD is defined as the last dose level(s) below the NTD with 0 or 1 out of 6 evaluable subjects 
experiencing a DLT in Cycle 1 during dose escalation.  An intermediate dose cohort of CC-90009
(one between the NTD and the last dosing schedule before the NTD) or a variable dose cohort (eg, 
less frequent dosing) may be evaluated to accurately determine the MTD at the discretion of the 
SRC.  
7.2.6
Definition of Dose-Limiting Toxicity 
During dose escalation, the DLT assessment period is Cycle 1 (at least 28 days and up to 42 days). 
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), 
Version 4.03 are used as a guide for the grading of severity of adverse events.  
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A DLT is defined as any of the following toxicities occurring within the DLT assessment unless 
the event can clearly be determined to be unrelated to CC-90009. Dose-limiting toxicities are 
described below:

Any non-hematologic toxicity Grade ≥ 3 EXCEPT for:  

Grade ≥ 3 nausea, vomiting, dehydration, or diarrhea that responds to standard of care.

Grade ≥ 3 fatigue which resolves to Grade ≤ 2 within 7 days (with optimal medical 
management).

Grade ≥ 3 infection.

Grade 3 TLS, if controlled by medical management.

Grade 3 electrolyte abnormalities other than hypocalcemia (see below) correctable with 
supportive therapy.

Grade 3 laboratory evidence of hypocalcemia of < 24 hours duration in the absence of 
Grade ≥ 3 clinical symptoms of hypocalcemia.

Grade ≥ 3 AST or ALT elevation lasting ≤ 7 days.
o
NOTE:  any Grade ≥ 3 AST or ALT in the setting of bilirubin elevation > 2xULN
(> 2x baseline for subjects with Gilbert’s syndrome) will be a DLT.

Hematological toxicities as follows:

Prolonged myelosuppression, ie, marrow cellularity < 5% or persistent Grade ≥ 3 
neutropenia at Cycle 1 Day 42 in the absence of leukemia. 

Any AE, unless clearly determined to be unrelated to the drug, and necessitating dose-level 
reduction during Cycle 1. 
Isolated laboratory changes without associated clinical signs or symptoms (eg, hypomagnesemia, 
hypermagnesemia, hypoalbuminemia, hypophosphatemia, and lymphocyte count increased or 
decreased) may not be included in this definition.  These findings will be discussed and reviewed 
by the SRC.
7.2.7
Criteria for Dose Escalation in the Next Cohort of Subjects
Upon completion of the accelerated phase (eg, at least 1 subject in each cohort), cohorts will consist 
of up to 6 evaluable subjects. The SRC will make dose escalation decisions.  The decision criteria 
for dose escalation are:

If no more than 0 of 3 or 1 of 6 evaluable subjects experience DLT within the DLT window in 
a dose cohort, dose escalation to the next higher dose cohort may occur. Additional subjects 
will be enrolled to expand the cohort to 6 evaluable subjects if less than 6 subjects are evaluable 
when the DLT is observed.

If 2 or more of up to 6 evaluable subjects experience a DLT within the DLT window in a dose 
cohort, any further recruitment will cease and this dose will be defined as the NTD.

SRC will determine if additional subjects will be enrolled at lower dose cohorts to have 6 
evaluable subjects in order to define MTD, or whether an intermediate dose cohort or 
alternative schedule will be explored in up to 6 newly enrolled subjects.  
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The number of cohorts depends on incidence of DLT.  A subject may experience more than 
one DLT.  Dose escalation decisions are based on the number of subjects experiencing DLT 
events.
7.2.8
Definition of Stopping Criteria
During Part A, dose escalation stops when ≥ 2 of up to 6 evaluable subjects in any dose cohort 
experience DLT during the DLT window. 
During Part B, non-binding Bayesian stopping rules will be used to continuously monitor for 
excess toxicity defined as the occurrence of AEs during any cycle that would fulfill the DLT 
criteria specified in Part A or AEs leading to dose reduction or treatment discontinuation or AEs 
of sepsis. Details regarding the stopping rules are described in Section 9.9.3.
The SRC will convene regularly to review all the available safety, PK, PD, and efficacy data as 
well as the results of the Bayesian analysis of excess toxicity and in the event of the following:

Bayesian stopping criteria are met.

Unanticipated SAEs that are related to study treatment are reported.

Death attributable to study treatment is reported.

The sponsor or IRB/EC decides that subject safety may be compromised by continuing the 
study.
Decisions to stop the enrollment or terminate the study will be communicated promptly to 
investigators, to the Institutional Review Boards (IRBs)/Ethics Committees (ECs), Institutional 
Biosafety Committees ([IBCs], if applicable), and to the appropriate regulatory authorities.
7.2.9
Permitted Study Drug Adjustments
Dose reductions are permitted in any cycle, including Cycle 1.  Dose reductions that occur in Cycle 
1 during dose escalation will constitute DLT as outlined in Section 7.2.6, but subjects will be 
allowed to continue on CC-90009 at a reduced dose.  
When a dose reduction is indicated, the CC-90009 dose from the next lower dose cohort will be 
selected or a less frequent dosing schedule after discussion with the Medical Monitor. Subjects 
will dose reduce using the same formulation to which they are currently assigned (eg, Gen 1 
CC-90009 → Gen 1 CC-90009 and Gen 2b CC-90009 → Gen 2b CC-90009).  Two dose 
reductions are allowed.  Once the dose has been reduced, it can be escalated when toxicity reaches 
Grade ≤ 1.  If toxicity recurs at the higher dose, the dose will be reduced a second time, but no re-
escalation is then permitted. If any subject continues to experience unacceptable toxicity after two 
dose reductions (one for the starting dose), CC-90009 will be discontinued permanently.
Intra-subject dose escalation of CC-90009 is not permitted during Cycle 1, but escalation to a dose 
subsequently deemed to be tolerated in a higher dosing cohort may be permitted in later cycles if 
approved by the SRC.
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7.2.10
Criteria for Dose Reduction
Any AE meeting the definition of DLT will require dose reduction and/or interruption.  Doses 
should be delayed if any Grade ≥ 2 toxicities are not resolved to Grade ≤ 1 or baseline by the time 
of the next dose.  Chronic Grade 2 toxicity may warrant dose reduction of CC-90009.  Such cases 
should be discussed with the Sponsor before dosing changes are made.  Dose reductions should 
maintain the subject’s current CC-90009 formulation.
7.2.11
Criteria for Dose Increase
In Part A (escalation phase), intra-subject dose escalation beyond the doses initially assigned to a 
subject is not permitted in Cycle 1.  Those continuing to take CC-90009 beyond Cycle 1 may, 
following approval by the SRC, have the dose increased providing the alternative dose has been 
shown to be well tolerated by at least one cohort of subjects in this study. 
In Part B (expansion phase), no dose escalation beyond the MTD is allowed. 
7.2.12
Treatment Interruption/Delay for Adverse Events
In Cycle 1, all CC-90009 doses must be completed on or before Day 10 for the Days 1-5 and 
Days 1-7 schedule and Day 14 for a Days 1-10 dose schedule (80% of the total planned Cycle 1 
dose, eg, ≥ 4 doses for a Days 1-5, ≥ 6 doses for a Days 1-7, or ≥ 8 doses for a Days 1-10 dosing 
schedule in order to be evaluable for DLT during dose escalation). On the alternate D1-3/D8-10 
schedule, doses must be completed on or before the end of Day 14; 80% of the planned total Cycle 
1 dose, ≥5 doses in order to be evaluable for DLT during Part A).
If CC-90009 dosing is interrupted/delayed during the dosing days of Cycles ≥ 2, the doses of CC-
90009 may still be completed within the first 14 calendar days of that cycle. Dosing delays beyond 
Day 14 of Cycles ≥ 2 will require resuming CC-90009 dosing in the next cycle (if planned). 
Treatment cycles with CC-90009 may be interrupted up to 8 weeks until toxicity reaches either 
Grade ≤1 or baseline levels.  
Treatment may restart either at the same, or a reduced dose, at the Investigator’s discretion or as 
described in Section 7.2.9. Any such treatment interruptions/delays must be discussed with the 
Sponsor medical monitor.
7.2.13
Management of Select Adverse Events
7.2.13.1
Prophylaxis and Management of Tumor Lysis Syndrome
Treatment with cytolytic cancer therapies in the setting of high tumor burden may cause rapid 
tumor lysis and associated electrolyte and renal disturbance with risk of cardiac arrhythmia and 
sudden death.  
Tumor lysis syndrome (TLS) is manifested by rapid release of large amounts of potassium, 
phosphate 
and 
nucleic 
acids 
into 
the 
circulation 
with 
associated 
hyperkalemia, 
hyperphosphatemia, hyperuricemia, and hypocalcemia.  Precipitation of uric acid and calcium 
phosphate crystals in the renal tubules can result in acute kidney injury and electrolyte disturbances 
can trigger cardiac arrhythmias, seizures and sudden death.
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Final: 31 Mar 2022
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The risk of TLS with CC-90009 is unknown.  As a pre-emptive measure, subjects will be 
monitored closely for TLS following the administration of each dose of CC-90009.  Subjects 
should be admitted as inpatients during dosing in Cycle 1 and either admitted as inpatients
(Investigator’s discretion) or monitored in a LSU during dosing days of Cycle ≥2.  Subjects should 
be adequately hydrated (eg, 2 to 3 liters of oral or IV fluids per day) starting the day prior to CC-
90009 administration and continuing through each day of CC-90009 administration. Medications 
to prevent or treat TLS are permitted.  Medications may include hypouricemic agents (eg, 
allopurinol, rasburicase), diuretics, and phosphate and potassium binders.  Rasburicase is 
contraindicated in subjects with baseline G6PD deficiency.
Subjects with laboratory abnormalities suspicious for TLS should be managed with hypouricemic 
agents (eg, allopurinol or rasburicase), intravenous hydration and diuretics as necessary to 
maintain urine output, and correction of hyperkalemia and hyperphosphatemia, according to 
standard medical practice (refer to Appendix I).  Subjects with laboratory abnormalities suspicious 
for clinically significant TLS should be managed as inpatients.
7.2.13.2
Hypocalcemia
Alterations in serum chemistry parameters in the cynomolgus monkey studies included decreased 
serum protein, albumin, and calcium. Subjects will start calcium, calcitriol, and vitamin D 
supplements at least 3 days prior to starting CC-90009 and continue until ≥ 3 days after the last 
dose of CC-90009 in each cycle. Guidelines for the management of hypocalcemia are presented in
Table 11. If Grade ≥ 2 hypocalcemia or symptoms of hypocalcemia (eg, carpopedal spasm, tetany, 
seizures, etc) occur, the subject must be hospitalized. Also, if Grade ≥ 2 hypocalcemia and 
abnormal levels of serum albumin occurs, a serum ionized calcium test must be performed. If 
Grade ≥ 3 hypocalcemia persists for greater than 24 hours despite medical management or if any 
Grade ≥ 3 symptoms of hypocalcemia occur, study drug will be held until the hypocalcemia 
resolves to Grade ≤ 1. Study drug should be restarted at the next lower dose.
If Grade ≥ 2 hypocalcemia occurs in any cycle, subjects should be admitted as inpatients for the 
administration of CC-90009 during subsequent cycles (an exception can be made for subjects with 
grade 2 hypocalcemia lasting less than 24 hours that recovers without IV calcium [eg, calcium 
gluconate or calcium chloride] after discussion with the Celgene medical monitor). For these 
subjects, additional calcium monitoring on dosing days (eg, Days 1-5, Days 1-7, or Days 1-10) at 
6 and 12 hours (± 1 hour) postdose should be performed during Cycle ≥2.
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Table 11:
Management of Hypocalcemia
Corrected Serum Total Calciuma
Grade ≤ 1
Grade 2
Grade ≥ 3
≥ 8.0 mg/dL 
(≥2.0 mmol/L)
(ionized 
≥1.0 mmol/L)
< 8.0 – 7.5 mg/dL 
(< 2.0 – 1.88 
mmol/L)
(ionized < 1.0 –
0.95 mmol/L)
< 7.5 – 7.0 mg/dL 
(< 1.88 –
1.75 mmol/L)
(ionized < 0.95 –
0.9 mmol/L)
< 7.0 mg/dL 
(< 1.75 mmol/L)
(ionized 
< 0.9 mmol/L)
Hospitalization 
for monitoring
Not required
Monitor calcium as 
inpatient Q6 hours 
or as clinically 
indicated  until 
trending upwardb
Monitor calcium as 
inpatient Q6 hours 
or as clinically 
indicated until 
trending upwardb
Monitor calcium as 
inpatient Q6 hours 
or as clinically 
indicated until 
trending upwardb
IV calcium 
gluconatec
Not required
Administer as 
needed for acute 
symptomsd or 
prolonged QT
Administer as 
needed for acute 
symptomsd or 
prolonged QT
(consider in absence 
of symptoms if rapid 
decrease)
Administer as 
needed for acute 
symptomsd or 
prolonged QT
(consider in absence 
of symptoms if rapid 
decrease)
Oral calcium
1200-1500 mg of 
elemental calcium 
per day in divided 
doses
1200-1500 mg of 
elemental calcium 
per day in divided 
doses
2400-2500 mg of 
elemental calcium 
per day in divided 
doses
2400-2500 mg of 
elemental calcium 
per day in divided 
doses
Vitamin D 
therapy
calcitriol 0.25 μg 
QD
calcitriol 0.25 μg 
BID
calcitriol 0.5 μg BID
calcitriol 0.5 μg BID
AC = before meals; BID = twice a day; IV = intravenous; PO = by mouth; TID = three times a day.
a Corrected Ca (mg/dL) = Total Ca (mg/dL) – 0.8 [albumin (g/dL) – 4].
b Also check for concurrent hypomagnesemia and correct with supplementation if present.
c One to 2 g of calcium gluconate (= 90-180 mg elemental calcium), in 50 mL of saline infused over 10-20 min. This dose of 
calcium gluconate will raise the serum calcium for only 2-3 hours.  It should be followed by a slow infusion of calcium in 
patients with persistent hypocalcemia.
d For example, carpopedal spasms, tetany, seizures, etc.
7.2.13.3
Neutropenia and Anemia
Hematopoietic growth factors or other hematologic support, such as erythropoietin, darbepoetin, 
granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating 
factor, RBC- or platelet- transfusions are allowed in the study with therapeutic intent. Therapeutic 
use of G-CSF is allowed at any time for subjects experiencing Grade 3/4 neutropenia or any grade 
febrile neutropenia.  Prophylactic use of granulocyte (or granulocyte-macrophage) growth factors 
is not allowed during Cycle 1.
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Final: 31 Mar 2022
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Subjects with Grade 3 or 4 neutropenia should be monitored frequently with laboratory tests until 
resolution to Grade ≤ 1. Antimicrobial, antifungal, and antiviral prophylaxis should be considered
and provided per institutional standard medical practice.
7.2.13.4
Infection
Vigilance for the signs and symptoms of infection should be practiced and managed according to 
institutional standard medical practice.  Routine infectious disease prophylaxis including 
appropriate prophylactic antibiotic, antiviral, antipneumocystis, antifungal, or other prophylaxis 
should be implemented during the study according to institutional standard medical practice.
7.2.13.4.1
SARS-CoV-2 Infection
Subjects with confirmed SARS-CoV-2 infection following the start of CC-90009 administration 
must have treatment interrupted.
For confirmed SARS-CoV-2 infection, treatment may be resumed after:
1) at least 10 days (20 days for severe/critical illness) have passed since symptoms first appeared, 
positive RT-PCR test result, or positive viral antigen test result, 
2) resolution of acute symptoms (including at least 24 hours has passed since last fever without 
fever reducing medications), 
3) evaluation by the Investigator with confirmation that there are no sequelae that would place 
the participant at a higher risk of receiving investigational treatment, and 
4) consultation by the Sponsor Medical Monitor.
For suspected cases, treatment may resume if SARS-CoV-2 infection is ruled-out and other criteria 
to resume treatment are met. Prior to re-initiating on-study treatment in a subject with a dosing 
delay lasting more than 8 weeks due to SARS-CoV-2 infection, the Medical Monitor/designee 
must be consulted.
7.2.13.5
Pain
Tumor pain or treatment-induced pain can be controlled with opioid and opioid-related analgesics, 
such as codeine, meperidine, propoxyphene or morphine, administered at the clinician’s discretion, 
and as dictated by medical need. The risk of bleeding, especially in the setting of 
thrombocytopenia, should be considered prior to use of non-steroidal anti-inflammatory drugs and 
aspirin.
7.2.13.6
Diarrhea
It is recommended that subjects experiencing diarrhea be managed according to the guideline 
provided in Appendix J.  Antidiarrheal medication may be administered as prophylaxis and for 
treatment of diarrhea.  
7.2.13.7
Infusion Reactions
Infusion of a chemotherapeutic product may cause infusion reactions ranging from localized 
injection site reactions to severe and life-threatening reactions.  Infusion reactions may occur with 
the first or subsequent infusions and typically develop within 24 hours of infusion (Vogel, 2010).  
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Symptoms may include hypotension, tachycardia, dyspnea and respiratory symptoms 
(eg, bronchospasm, throat irritation, wheezing, and laryngeal edema).  Other possible symptoms 
include nausea, vomiting, diarrhea, hypertension, flushing, skin rash, urticaria, headache, fever 
and chills.  Full emergency resuscitation facilities should be immediately available and subjects 
should be under close supervision of the Investigator or appropriately trained staff during 
administration of CC-90009 and for at least 1 hour after.
Medical management of infusion reactions should be instituted according to standard medical 
practice using glucocorticoids, epinephrine, oxygen, intravenous fluids and other medications as 
medically indicated.  
7.2.13.8
Hypotension
Grade 2 and 3 hypotension TEAEs have occurred in subjects treated with CC-90009. Hypotension 
has been typically observed on or within 24 hours of the days of dosing. Standard CC-90009 dose 
interruption and modification guidance for non-hematologic toxicity Grade 3/4 AEs should be 
followed (Section 7.2.9).

Infection should be considered in all subjects presenting with hypotension (with or without 
fever) and appropriate cultures must be obtained and empiric antibiotic therapy initiated per 
institution standard of care. 

Grading of hypotension for this protocol has been clarified, as subjects are already hospitalized 
during days of dosing (Table 12 and Lee, 2014).

Management of Grade 2 hypotensiona:

IV fluids (eg, initially 500 to 1000 mL or per institutional guidance)

Addition of anakinra 100 mg administered by subcutaneous injection (recombinant, 
nonglycosylated human interleukin-1 receptor antagonist [IL-1Ra]). Anakinra should be 
administered Q12 hours (or per institutional practice for management of CRS) until 
resolution of CC-90009-related hypotension

Consider adding dexamethasone (eg, 10 mg IV, Q12 hours until resolution or per 
institutional guidance)

Management of Grade ≥3 hypotensiona:

If unresponsive to IV fluids and anakinra, consider escalation to higher level of medical 
care (eg, intensive care unit) and adding single low-dose vasopressor

Addition of high-dose or multiple vasopressors if unresponsive to single low-dose 
vasopressor (Table 13)
a The management of Grade ≥ 2 CC-90009 associated hypotension should be as per local institution clinical practice 
guidelines. 
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Celgene Corporation
CC-90009-AML-001 Amendment 9
Final: 31 Mar 2022
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Table 12:
Modified Grading for Hypotension for CC-90009
Systolic 
Blood 
Pressure (SBP) 
< 90 mm Hg
Grade 1
Grade 2
Grade 3
Grade 4
Study Specific 
Grading
Asymptomatic, 
intervention not 
indicated 
Responds to 
intravenous (IV) 
fluids and/or anti-
cytokine therapy 
(eg, anakinra, 
steroids)
Needs IV 
vasopressor(s)
Life-threatening
Table 13:
High-dose Vasopressors (all doses are required for ≥ 3 hours)
Pressor
Dose
Norepinephrine monotherapy
≥ 20 μg/min
Dopamine monotherapy
≥ 10 μg/kg/min
Phenylephrine monotherapy
≥ 200 μg/min
Epinephrine monotherapy
≥ 10 μg/min
If on vasopressin
Vasopressin + norepinephrine equivalent
of ≥10 μg/min*
If on combination vasopressors (not vasopressin)
Norepinephrine equivalent of ≥20 μg/min*
Source: Lee, 2014.
* VASST Trial vasopressor equivalent equation: norepinephrine equivalent dose = [norepinephrine (μg/min)/2] +
[dopamine (μg/kg/min) / 2] + [epinephrine (μg/min)] + [phenylephrine (μg/min) /10].
7.2.14
Definition of Overdose
Overdose, as defined for this protocol, refers to CC-90009 dosing only. On a per dose basis, an 
overdose is defined as the following amount over the protocol-specified dose of CC-90009
assigned to a given subject, regardless of any associated adverse events or sequelae:

10% over the protocol-specified dose
On a schedule or frequency basis, an overdose is defined as anything more frequent than the 
protocol required schedule or frequency.  
Complete data about drug administration, including any overdose, regardless of whether the 
overdose was accidental or intentional, should be reported in the case report form. Refer to 
Section 10 for the reporting of adverse events associated with overdose.
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7.2.15
Dosage Modifications for Concomitant Use of Strong CYP3A4 Inhibitors
in Part B Dose Expansion
In Part B, dosage modification of CC-90009 based on concomitant use with a strong CYP3A4
inhibitor (See Section 8.2 for list of example CYP3A4 inhibitors) will be as follows: 

For 3.0 mg Days 1-7 cohort, reduce CC-90009 dose to 2.0 mg

For 2.4 mg Days 1-7 cohort, reduce CC-90009 dose to 1.5 mg
Resume the CC-90009 dosage that was used prior to concomitant use of a strong CYP3A4 inhibitor 
3 days after discontinuation of the inhibitor.
No dose modification is required for concomitant use of moderate CYP3A4 inhibitors.
7.3
Method of Treatment Assignment
Subjects will be enrolled sequentially in Part A with no more than one subject enrolled per day 
into dose escalation cohorts.  Enrollment in Part B will be stratified by disease cohort and dosing 
schedule, as applicable.
An IRT system will be used to track subject assignments to the dose levels in dose escalation (Part 
A) and cohorts in dose expansion (Part B).
7.4
Packaging and Labeling
The label(s) for CC-90009 will include sponsor name, address and telephone number, the protocol 
number, dosage form and strength (where applicable), lot number, expiry date (where applicable), 
medication identification/kit number, dosing instructions, storage conditions, and required caution 
statements and/or regulatory statements as applicable. Additional information may be included on 
the label as applicable per local regulations. Gen 2b material will be clearly labeled as Gen 2b.  
Labeling for each formulation will be color coded as per the Pharmacy Manual for that 
formulation.
7.5
Investigational Product Accountability and Disposal 
Celgene (or designee) will review with the Investigator and relevant site personnel the process for 
investigational product return, disposal, and/or destruction including responsibilities for the site 
versus Celgene (or designee).
7.6
Investigational Product Compliance
Only the pharmacist or the Investigator’s designee will dispense CC-90009.  A record of the total 
dose (and number of vials used) of CC-90009 administered to each subject must be maintained.
The pharmacist or Investigator’s designee will document the doses dispensed/administered in the 
appropriate study records and the appropriate eCRF.
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8
CONCOMITANT MEDICATIONS AND PROCEDURES
All medications (excluding prior cancer therapy for the tumor under evaluation) taken beginning 
when the subject signs the ICD and all concomitant therapy during the study until 28 days after 
treatment discontinuation, together with dose, dose frequency and reasons for therapy use will be 
documented in the source documents and on the concomitant medication eCRF.  
All prior cancer therapy for the tumor under evaluation, including chemotherapy, biologic, 
immunologic, irradiation, and surgery, will be documented on dedicated prior cancer treatment 
eCRFs. 
The Investigator will instruct subjects to notify the study staff about any new medications taken 
after signing the ICD.  All medications and significant non-drug therapies (herbal medicines, 
physical therapy, etc.) and any changes in dosing with existing medications will be documented 
on the eCRFs.
8.1
Permitted Concomitant Medications and Procedures
Subject to the precautions described in Section 8.2, the use of any concomitant 
medication/therapies deemed necessary for the care of the subject should be used.  Repeat PK 
evaluations may be conducted if changes are made to concomitant medications suspected of 
affecting drug absorption or metabolism.
Medications to prevent or treat TLS are permitted.  Medications may include hypouricemic agents 
(eg, allopurinol, rasburicase), diuretics, and phosphate and potassium binders.  Rasburicase is 
contraindicated in subjects with screening G6PD deficiency.
Medications to treat infusion reactions are permitted.  Medications may include antihistamines, 
H2-blockers, anti-pyretics, corticosteroids, bronchodilators and other medications as medically 
indicated.
Routine prophylaxis with granulocyte colony stimulating factor or granulocyte-macrophage 
colony stimulating factor is allowed at the Investigator’s discretion after Cycle 1.  
Subjects receiving recombinant erythropoietin or darbepoetin alfa for at least 4 weeks prior to 
starting the CC-90009 may continue their pretreatment doses throughout the study.
Leukapheresis to control leukocytosis is permitted unless it is within the 2 weeks prior to the first 
dose of CC-90009. In Cycles 1-4, leukapheresis cannot be performed the same day as CC-90009 
dosing.
Hydroxyurea to control leukocytosis is permitted during screening and Cycle 1 at the Investigator’s
discretion.
Parenteral flu vaccination is permitted.  
Routine infectious disease prophylaxis including appropriate prophylactic antibiotic, antiviral, 
antipneumocystis, antifungal, or other prophylaxis should be implemented during the study 
according to institutional standard medical practice.  
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Subjects may receive approved or authorized COVID-19 vaccines while continuing on study 
treatment at the discretion of the Investigator. COVID-19 vaccines that are NOT live are allowed 
and should be handled in the same manner as other vaccines. Administration may occur during the 
study, including during the administration of the BMS study treatment and after the last 
administration of the BMS study treatment.
Treatment of active SARS-CoV-2 infections or high risk exposures, including use of 
investigational therapies, is allowed and should be discussed with the Sponsor Medical Monitor.
Even though CC-90009 is not anticipated to cause drug interactions when administered with 
CYP2C9 and CYP2C19 substrates at clinically relevant concentrations, caution should be used 
with narrow therapeutic index substrates such as warfarin, clopidogrel, voriconazole, phenytoin, 
fluindione and acenocoumarol, consistent with general clinical practice.
8.2
Prohibited Concomitant Medications and Procedures
Other investigational therapies must not be used while the subject is on the study.
Anticancer therapy (chemotherapy, biologic or investigational therapy, and surgery), other than 
the study treatments and hydroxyurea during Cycle 1, must not be given to subjects while the 
subject is on the study.  If such treatment is required the subject must be discontinued from the 
study.  Focal palliative radiotherapy for treatment of cancer-related symptoms is allowed during 
study treatment at the discretion of the Investigator.  Maintenance hormonal therapies are allowed 
in subjects with a history of breast or prostate cancer.
Treatment with chronic, therapeutic dosing of anti-coagulants (eg, warfarin, low molecular weight 
heparin, Factor Xa inhibitors) should be used with caution based on an overall risk-benefit 
assessment.  Short-term, prophylactic dosing of anticoagulants may be considered in subjects if 
medically indicated (eg, hospitalized patients, post-operatively).
Administration of investigational (not approved or authorized by relevant health authorities) 
COVID-19 vaccines is not allowed during the study. Live COVID-19 vaccines should not be 
administered to a subject during the study, including during the treatment, safety follow-up period 
and within 3 months following the last dose of study drug. In addition, the administration of a live 
COVID-19 vaccine is prohibited at least 14 days prior to initiation of study treatment.
Concomitant use with a strong CYP3A4 inhibitor increases CC-90009 exposure, which may 
increase CC-90009 toxicities, including the risk of sepsis. Avoid concomitant use of CC-90009 
with strong CYP3A4 inhibitors if possible. Alternative treatments for anti-fungal prophylaxis or 
medication (eg, micafungin, caspofungin, or amphotericin) should be considered. If concomitant 
use of strong CYP3A4 inhibitors is unavoidable during study treatment, CC-90009 dose reductions 
are required (Section 7.2.15) and subjects should be monitored closely for signs of toxicities. 
Subjects can resume CC-90009 at the dose used prior to initiation of the concomitant strong 
CYP3A4 inhibitor 3 days after discontinuation of the inhibitor.

Examples of strong CYP3A4 inhibiting medications: Atazanavir, boceprevir, clarithromycin, 
cobicistat, conivaptan, danoprevir/ritonavir, darunavir, elvitegravir/ritonavir, indinavir, 
itraconazole, ketoconazole,
lonafarnib,
lopinavir/ritonavir, 
mibefradil, 
mifepristone, 
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nefazodone, nelfinavir, paritaprevir/ritonavir combinations, posaconazole, ritonavir, 
saquinavir, telaprevir, telithromycin, tipranavir/ritonavir, troleandomycin, voriconazole 
Concomitant use with a strong or moderate CYP3A4 inducer may decrease CC-90009 efficacy. 
Avoid concomitant use of CC-90009 with strong or moderate CYP3A4 inducers. Alternative 
treatments with less CYP3A4 induction should be considered.

Strong CYP3A4 inducers: avasimibe, carbamazepine (Tegretol®), enzalutamine, mitotane, 
phenytoin (Dilantin®), rifampin (Rifadin®), St. John’s wort

Moderate CYP3A4 inducers: bosentan, efavirenz, etravirine, modafinil, nafcillin
8.3
Required Concomitant Medications and Procedures
All subjects will be required to start calcium, calcitriol, and vitamin D supplementation at least 
3 days prior to the first dose of CC-90009 in each cycle and continue until ≥ 3 days after the last 
dose of CC-90009 in each cycle. Supplementation may be extended if hypocalcemia occurs (refer 
to Section 7.2.13.2). Subjects will document (date and time) taking the supplements on diary cards 
that will be reviewed on Day 1 of each cycle and at the EOT visit.
The calcium/calcitriol/vitamin D supplementation regimen is:

Calcium carbonate 500 mg elemental calcium PO 3 TID (taken after meals to increase 
absorption)

Alternative preparations of calcium can be substituted but they must equal at least 1200 
mg of elemental calcium per day given in divided doses (eg, TID).

If the subject is on a proton pump inhibitor (PPI) or has gastric achlorhydria, then 
administer calcium citrate 630 mg elemental calcium PO TID or closest higher dose based 
on available strengths.

Calcitriol 0.25 micrograms PO QD

Vitamin D supplementation is based on the Screening serum 25-hydroxyvitamin D level:

Level < 12 ng/mL – excluded from the study

Level 12 – 20 ng/mL – Vitamin D3 or D2 50,000 IU weekly

Level > 20 ng/mL– Vitamin D3 or D2 1000 IU QD
The risk of TLS with CC-90009 is unknown.  Subjects should be adequately hydrated (eg, 2 to 
3 liters of oral or IV fluids per day) starting the day prior to CC-90009 administration and 
continuing through each day of CC-90009 administration.
Subjects given CC-90009 at daily doses ≥ 3.6 mg will be administered concurrent dexamethasone
per Section 7.2. Subjects enrolled on other dose levels may be administered corticosteroid 
premedication as per SRC recommendation (eg, at the 3.0 mg dose level on the Days 1-7 and Days 
1-10 schedules).
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Routine infectious disease prophylaxis including appropriate prophylactic antibiotic, antiviral, 
anti-pneumocystis, antifungal, or other prophylaxis should be implemented during the study 
according to institutional standard medical practice.
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9
STATISTICAL CONSIDERATIONS
9.1
Overview
The primary objectives of this Phase 1 study are to determine the safety and tolerability of 
CC-90009, and to define the NTD, MTD, and/or the RP2D of CC-90009.  The secondary 
objectives are to provide information on the preliminary efficacy of CC-90009 in R/R AML and 
R/R HR-MDS, and to characterize the PK of CC-90009 in plasma and urine.
Data summaries/statistical analyses will be performed by study phase, dose level/dosing regimen 
and cohort as needed or applicable in the dose escalation phase (Part A) and dose expansion phase 
(Part B) separately, as well as at dosing regimen(s) used for expansion that include the subjects 
from both study phases. For retreated subjects, the safety data collected during the initial and the 
retreated period will be combined for the analysis. The efficacy data will be analyzed and reported 
for the initial treatment period only.  
9.2
Study Population Definitions
The study population definitions are as follows: 

Enrolled Population – All subjects who meet all the inclusion/exclusion criteria and are eligible 
for the study. 

Treated Population – All subjects who enroll and receive at least one dose of CC-90009.

Efficacy Evaluable (EE) Population – All subjects who enroll in the study, meet eligibility 
criteria, complete at least one cycle treatment or receive at least 80% of scheduled dose in 
Cycle 1, have a baseline leukemia assessment evaluation and at least one valid post-baseline 
leukemia assessment. 

Pharmacokinetic (PK) Evaluable Population – all subjects who enroll and receive at least one 
dose of CC-90009 and have at least one measurable concentration of CC-90009.

Biomarker Evaluable (BE) Population – all subjects who enroll, receive at least one dose of 
study drug, and have at least one biomarker assessment, excluding disqualified assessments.
9.3
Sample Size and Power Considerations
During Part A (dose escalation) of the study, a modified accelerated titration design (Simon, 1997) 
will be used for dose escalation as described in Section 7.2.  The total number of subjects in Part 
1 will depend on the number of dose escalations required to reach the NTD and cannot be 
determined in advance.  However, the anticipated number of subjects will be approximately 40 to 
60.
Following completion of dose escalation (Part A), one or more dosing regimens may be selected 
with up to approximately 20 evaluable subjects each for R/R AML or R/R HR-MDS at each 
selected dosing regimen for an expansion phase (Part B).  Expansion may occur at the MTD and 
schedule established in the dose escalation phase, and/or at an alternative tolerable dose and 
schedule, based on review of safety, PK, and PD data from Part A.  Sample sizes are not determined 
based on power calculation but rather on clinical, empirical and practical considerations 
traditionally used for exploratory studies of this kind.  
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At least 13 efficacy evaluable subjects with R/R AML in Part B will be accrued. If the response 
rate is 30% or more, the probability of seeing no response in the first 13 R/R AML subjects will 
be less than 1% (Gehan, 1961).  If no response is observed out of 13 R/R AML subjects, the 
enrollment for this cohort will stop for futility.  Otherwise, the enrollment will be expanded to up 
to approximately 20 evaluable subjects each for R/R AML or R/R HR-MDS for this cohort. The 
2-sided 95% confidence interval for 20% and 30% response rate is tabulated in Table 14 for 
different sample size scenarios.
Table 14:
Confidence Interval for 20% and 30% Response Rate for Different 
Scenarios of Sample Size (Wilson score interval)
CI
Response rate
Sample size
13
20
30
40
0.95
0.2
(0.066 ,0.471)
(0.081 ,0.416)
(0.095 ,0.373)
(0.105 ,0.348)
0.95
0.3
(0.122 ,0.569)
(0.145 ,0.519)
(0.167 ,0.479)
(0.181 ,0.454)
CI = confidence interval.
Source:  Gehan, 1961.
9.4
Background and Demographic Characteristics
Subjects’ age, weight, height and other continuous demographic and baseline variables will be 
summarized using descriptive statistics.  Gender, race and other categorical variables will be 
summarized with frequency tabulations.  Medical history data will be summarized using frequency 
tabulations by system organ class and preferred term.  Prior therapies will be summarized by 
frequency tabulation, if available.  Supportive corresponding subject listings will also be provided.
9.5
Subject Disposition
Subject disposition (analysis population allocation, on-going, discontinued from treatment and/or 
study, along with primary reason for discontinuation) will be summarized using frequency and 
percent.  A summary of subjects enrolled by site will be provided.  Protocol violations will be 
summarized using frequency tabulations.  Supportive corresponding subject listings will also be 
provided.
9.6
Efficacy Analysis
Efficacy analyses will be based on the Treated Population and certain efficacy analyses will also 
be performed on the EE Population.  Leukemia response will be determined by the Investigator 
based on the IWG Response Criteria in AML (Cheson, 2003; refer to Appendix C). MDS response 
will be based on the IWG Response Criteria for Myelodysplasia (Cheson, 2006; refer to Appendix 
G). Efficacy endpoints include complete remission rate (CRR), objective response rate (ORR), 
and time-to-event efficacy variables.
9.6.1
Complete Remission Rate and Objective Response Rate
The CRR is defined as the rate for any type of CR.  The ORR is defined as the rate for all response 
categories, including all types of CRs, MLFS, and PR for AML. For MDS, the ORR includes all 
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responses (CR, mCR and PR).  The efficacy variable of focus will be ORR and CRR. Other 
measures of clinical activity including overall survival (OS), relapse-free survival (RFS), 
progression-free survival (PFS), event-free survival, duration of remission, duration of response, 
time to transformation to AML (HR-MDS subjects only) and time to remission/response will be 
summarized. Overall response rate and CRR will be summarized using frequency tabulation.  Two-
sided 95% Clopper-Pearson exact confidence intervals (Clopper, 1934) will be provided for ORR 
and CRR estimates.
9.6.2
Time to Event Variables
Other measures of clinical activity including overall survival (OS), relapse-free survival (RFS), 
progression-free survival (PFS), event-free survival, duration of remission, duration of response 
and time to remission/response will be summarized.  Subjects who have completed the treatment 
phase without documented progression of disease will have efficacy evaluations performed as 
specified in Section 6.3.2. Subjects will be followed for overall survival as specified in 
Section 6.3.3.
The Kaplan-Meier estimate of the median of RFS, PFS, and OS along with their 95% confidence 
interval will be provided (Brookmeyer, 1982).  The RFS, PFS, and OS rates at selected time points
will be computed using the Kaplan-Meier estimates, along with standard errors of rate 
(Greenwood’s formula, Klein, 2003).  Duration of remission/response and time to 
remission/response will also be reported in subjects who achieve remission/response, using tumor 
specific evaluation criteria.
MDS cohort in Part B
For the HR-MDS cohort, transformation to AML and time to transformation to AML will be 
summarized. 
Listings and graphical displays will be provided where useful for the interpretation of results.
Full details on the efficacy analysis are described in the Statistical Analysis Plan (SAP).
9.7
Safety Analysis
Adverse events, including treatment-emergent adverse events (TEAEs), laboratory assessments, 
vital signs, ECG results, ECOG performance status, LVEF assessments, physical examinations, 
vital signs, exposure to study treatment, assessment of concomitant medications, and pregnancy 
testing for females of child bearing potential will be summarized for the Treated Population.
Adverse events observed will be classified using the Medical Dictionary for Regulatory Activities 
(MedDRA).  The severity of the toxicities will be graded according to the NCI CTCAE (Version 
4.03) whenever possible.  The frequencies of adverse events will be tabulated by MedDRA 
(Version 17.1 or higher) System Organ Class and Preferred Term.  In the by-subject analysis, a 
subject having the same AE more than once will be counted only once.  Adverse events will also 
be summarized by NCI CTCAE grade.  Adverse events leading to dose reduction/interruption or 
permanent discontinuation of study treatment, events classified as CTCAE Grade 3 or 4, study 
drug-related AEs, deaths, and SAEs will be tabulated.  By-subject listings of all AEs, deaths, and 
SAEs and their attribution will be provided.  
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Clinical laboratory results will be summarized descriptively, which will include a display of 
change from baseline.  Bidirectional shift tables (low and high) demonstrating the change of 
CTCAE grades from baseline to the worst post-baseline severity grade during the treatment period 
will also be presented for applicable tests.  Listings of abnormal clinical laboratory data according 
to NCI CTCAE severity grades (if applicable), abnormal flags (low or high) and clinical 
significance of the latter will be provided.  Graphical displays (eg, “spaghetti” plots or box plots) 
will be provided for key laboratory tests.
Descriptive statistics for ECG, vital sign and LVEF measurement, both observed values and 
changes from baseline, will be summarized.  Shift tables demonstrating the changes from baseline 
to the worst post-baseline qualitative assessment of abnormality will be displayed in cross-
tabulations.  Post-baseline abnormal ECG and LVEF values will be summarized using frequency 
tabulations.  ECG, vital sign and LVEF measurements will be listed by subject. 
Graphical displays will be provided where useful in the interpretation of results.
9.8
Interim Analysis
No formal interim analysis is planned.  Data will be reviewed on an ongoing basis.
9.9
Other Topics
9.9.1
Assessment of Pharmacokinetics
Noncompartmental plasma PK parameters of CC-90009, such as Cmax, AUC24, CL, Vss, and t1/2, 
will be estimated and summarized by dose level and visit, when feasible. Selected plasma PK 
parameters (eg, Cmax, AUC24, and t1/2,) will be estimated and summarized for the R- and S-
enantiomers of CC-90009, respectively. Urine PK parameters of CC-90009, such as Fe and CLR, 
will be estimated and summarized for the RP2D.  Main plasma and urine PK parameters as 
described above will also be estimated for hydroxypropyl-β-cyclodextrin at the RP2D. Other PK 
parameters may be calculated as appropriate.
Descriptive statistics (number of subjects [N], mean, standard deviation [SD], coefficient of 
variation [CV%], geometric mean, geometric CV%, median, minimum, and maximum) will be 
provided for drug concentration data and PK parameters. Results will be presented in tabular 
and/or graphic forms as appropriate.
A population PK analysis for CC-90009 may be conducted using both intensive and sparse PK 
samples to explore the inter-individual variability of plasma drug exposure and the contributing 
factors (covariates).  The relationship between CC-90009 doses, plasma exposures, and selected 
clinical endpoints (eg, measures of toxicities, effectiveness, and/or biomarkers) may be explored
as appropriate. The population PK model, in combination with the knowledge on exposure-
response, may be used to explore dosing regimens for Part B or phase 2 studies.
9.9.2
Assessment of Pharmacodynamics
Descriptive statistics (N, mean, standard deviation, median, min, and max) will be provided for 
baseline, post-baseline values, and changes from baseline or percent change from baseline of each 
biomarker.  Subjects’ biomarker results changing over time will be plotted.  Comparison of 
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biomarker levels before and during treatment will be performed by Wilcoxon signed rank test.  If 
sufficient and valid results from biomarker assays can be obtained, the relationship between 
biomarker levels and PK or clinical endpoints including CRR, ORR and time-to-event variables 
will be explored.
9.9.3
Stopping Rules Regarding Toxicity in Part B Dose Expansion
During dose expansion phase (Part B), a non-binding Bayesian method will be utilized to monitor 
excess toxicities defined as the occurrence of AEs during any cycle that would fulfill the DLT 
criteria specified in Part A or treatment related AEs leading to dose reduction or discontinuation
or the occurrence of sepsis. The enrollment in the corresponding expansion cohort will pause to 
ensure the posterior probability of excess toxicity rate exceeding 25% is not more than 70%, ie, 
when
Prob (rate of AEs that fulfill the DLT criteria or treatment-related AEs leading to dose reduction 
or discontinuation or rate of sepsis >0.25|data, a, b) > 0.7.
Where a, b are parameters of Beta distribution. Weakly informative priors, ie, Beta (0.5, 0.5), may 
be used to calculate the posterior probability. The excess toxicity rate of 25% is established based 
on clinical inputs with threshold of 70% based on empirical data analysis.
After a minimum of 8 subjects have enrolled and taken at least one cycle of study treatment for a 
cohort, the posterior distributions of excess toxicity will be calculated on a continuous basis for
every subject enrolled (Table 15).
The operating characteristics of the proposed Bayesian safety monitoring plan are detailed in 
Appendix P.
Table 15:
Stop Boundaries Based on Stopping Criteria for Each Expansion 
Cohort
Number of Subjects
Number of Subjects with AEs fulfilling DLT or 
other criteria that would prompt potential 
enrollment pause
8
3
10
4
13
5
17
6
21
7
24
8
28
9
32
10
35
11
39
12
AE = adverse event; DLT = dose limiting toxicity
Note: Only unique stopping boundaries are presented up to the estimated maximum enrollment of 40 subjects in an 
expansion cohort.
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The SRC will convene regularly (eg, monthly) to review the overall safety/tolerability data and to 
assess the Bayesian analysis output. Each subject that experiences an AE that meets the above 
criteria will be reviewed by the SRC, and the overall Bayesian Analysis will be run at that time to 
guide the SRC on cohort decisions. If the stopping rule is triggered, the SRC will conduct a 
comprehensive review of available safety, PK, PD, and preliminary efficacy data to make 
continuation decisions. Decisions to pause enrollment of specific expansion cohort(s) or terminate 
the study will be determined by the SRC and communicated properly to Investigators, IRBs, and 
appropriate regulatory authorities.  
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10
ADVERSE EVENTS
10.1
Monitoring, Recording and Reporting of Adverse Events
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in 
a subject during the course of a study. It may be a new intercurrent illness, a worsening 
concomitant illness, an injury, or any concomitant impairment of the subject’s health, including 
laboratory test values (as specified by the criteria in Section 10.3), regardless of etiology. Any 
worsening (ie, any clinically significant adverse change in the frequency or intensity of a pre-
existing condition) should be considered an AE. A diagnosis or syndrome should be recorded on 
the AE page of the eCRF rather than the individual signs or symptoms of the diagnosis or 
syndrome. 
Abuse, withdrawal, sensitivity or toxicity to an investigational product should be reported as an 
AE. Overdose, accidental or intentional, whether or not it is associated with an AE should be 
reported on the overdose eCRF (refer to Section 7.2.14 for the definition of overdose). Any sequela 
of an accidental or intentional overdose of an investigational product should be reported as an AE 
on the AE eCRF. If the sequela of an overdose is an SAE, then the sequela must be reported on an 
SAE report form and on the AE eCRF. The overdose resulting in the SAE should be identified as 
the cause of the event on the SAE report form and eCRF but should not be reported as an SAE 
itself.
In the event of overdose, the subject should be monitored as appropriate and should receive 
supportive measures as necessary. There is no known specific antidote for CC-90009 overdose. 
Actual treatment should depend on the severity of the clinical situation and the judgment and 
experience of the treating physician.
All subjects will be monitored for AEs during the study. Assessments may include monitoring of 
any or all of the following parameters:  the subject’s clinical symptoms, laboratory, pathological, 
radiological or surgical findings, physical examination findings, or findings from other tests and/or 
procedures.
All AEs will be recorded by the Investigator from the time the subject signs informed consent until 
28 days after the last dose of CC-90009 as well as those SAEs made known to the Investigator at 
any time thereafter that are suspected of being related to CC-90009. AEs and SAEs will be 
recorded in the eCRF and in the subject’s source documents. Refer to Section 10.5 for instructions 
on how to report SAEs to Celgene Drug Safety.
Subjects will be followed for all SAEs, and all AEs (SAEs and non-serious AEs) associated with 
confirmed or suspected SARS-CoV-2 infection until resolution, the condition stabilizes, the event 
is otherwise explained, the event is deemed irreversible, the subject is lost to follow-up, or for 
suspected cases, until SARS-CoV-2 infection is ruled-out.  
10.2
Evaluation of Adverse Events
A qualified Investigator will evaluate all adverse events as to: 
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10.2.1
Seriousness 
An SAE is any AE occurring at any dose that:

Results in death;

Is life-threatening (ie, in the opinion of the Investigator, the subject is at immediate risk of 
death from the AE);

Requires inpatient hospitalization or prolongation of existing hospitalization (hospitalization 
is defined as an inpatient admission, regardless of length of stay);

Results in persistent or significant disability/incapacity (a substantial disruption of the subject’s 
ability to conduct normal life functions);

Is a congenital anomaly/birth defect;

Constitutes an important medical event.
Important medical events are defined as those occurrences that may not be immediately life-
threatening or result in death, hospitalization, or disability, but may jeopardize the subject or 
require medical or surgical intervention to prevent one of the other outcomes listed above.  Medical 
and scientific judgment should be exercised in deciding whether such an AE should be considered
serious.
Events not considered to be SAEs are hospitalizations for:

a standard procedure for protocol therapy administration.  However, hospitalization or 
prolonged hospitalization for a complication of therapy administration will be reported as an 
SAE. 

routine treatment or monitoring of the studied indication not associated with any deterioration 
in condition.

the administration of blood or platelet transfusion as routine treatment of studied indication.  
However, hospitalization or prolonged hospitalization for a complication of such transfusion 
remains a reportable SAE.

a procedure for protocol/disease-related investigations (eg, surgery, scans, endoscopy, 
sampling for laboratory tests, bone marrow sampling).  However, hospitalization or prolonged 
hospitalization for a complication of such procedures remains a reportable SAE.

hospitalization or prolongation of hospitalization for technical, practical, or social reasons, in 
absence of an AE.

a procedure that is planned (ie, planned prior to start of treatment on study); must be 
documented in the source document and the eCRF.  Hospitalization or prolonged 
hospitalization for a complication remains a reportable SAE.

an elective treatment of or an elective procedure for a pre-existing condition, unrelated to the 
studied indication that has not worsened from baseline. 

emergency outpatient treatment or observation that does not result in admission, unless 
fulfilling other seriousness criteria above.
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If an AE is considered serious, both the AE page/screen of the eCRF and the SAE Report Form 
must be completed.
For each SAE, the Investigator will provide information on severity, start and stop dates, 
relationship to the IP, action taken regarding the IP, and outcome.
10.2.2
Severity/Intensity
For both AEs and SAEs, the Investigator must assess the severity/ intensity of the event. 
The severity/intensity of AEs will be graded based upon the subject’s symptoms according to the 
current 
active 
minor 
version 
of 
the 
CTCAE, 
Version 
4.03; 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40
AEs that are not defined in the CTCAE should be evaluated for severity/intensity according to the 
following scale:

Grade 1 = Mild – transient or mild discomfort; no limitation in activity; no medical 
intervention/therapy required

Grade 2 = Moderate – mild to moderate limitation in activity, some assistance may be needed; 
no or minimal medical intervention/therapy required

Grade 3 = Severe – marked limitation in activity, some assistance usually required; medical 
intervention/therapy required, hospitalization is possible

Grade 4 = Life-threatening – extreme limitation in activity, significant assistance required; 
significant medical intervention/therapy required, hospitalization or hospice care probable

Grade 5 = Death – the event results in death
The term “severe” is often used to describe the intensity of a specific event (as in mild, moderate 
or severe myocardial infarction); the event itself, however, may be of relatively minor medical 
significance (such as severe headache).  This criterion is not the same as “serious” which is based 
on subject/event outcome or action criteria associated with events that pose a threat to a subject’s 
life or functioning.  
Seriousness, not severity, serves as a guide for defining regulatory obligations.
10.2.3
Causality
The Investigator must determine the relationship between the administration of the CC-90009 and 
the occurrence of an AE/SAE as Not Suspected or Suspected as defined below:
Not suspected:
a causal relationship of the adverse event to CC-90009
administration is unlikely or remote, or other medications, 
therapeutic interventions, or underlying conditions provide a 
sufficient explanation for the observed event.
Suspected:
there is a reasonable possibility that the administration of 
CC-90009 caused the adverse event.  ‘Reasonable possibility’ 
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means there is evidence to suggest a causal relationship between 
the IP and the adverse event.
Causality should be assessed and provided for every AE/SAE based on currently available 
information.  Causality is to be reassessed and provided as additional information becomes 
available.
If an event is assessed as suspected of being related to a comparator, ancillary or additional 
CC-90009 that has not been manufactured or provided by Celgene, please provide the name of the 
manufacturer when reporting the event.
10.2.4
Duration
For both AEs and SAEs, the Investigator will provide a record of the start and stop dates of the 
event.
10.2.5
Action Taken
The Investigator will report the action taken with IP as a result of an AE or SAE, as applicable (eg, 
discontinuation, interruption, or dose reduction of IP, as appropriate) and report if concomitant 
and/or additional treatments were given for the event. 
10.2.6
Outcome
The Investigator will report the outcome of the event for both AEs and SAEs.
All SAEs that have not resolved upon discontinuation of the subject’s participation in the study 
must be followed until recovered (returned to baseline), recovered with sequelae, or death (due to 
the SAE).
10.3
Abnormal Laboratory Values
An abnormal laboratory value is considered to be an AE if the abnormality:

results in discontinuation from the study;

requires treatment, modification/ interruption of CC-90009 dose, or any other therapeutic 
intervention; or

is judged to be of significant clinical importance, eg, one that indicates a new disease process 
and/or organ toxicity, or is an exacerbation or worsening of an existing condition.
Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness criterion need 
to be documented as a serious adverse event.
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the diagnosis 
or syndrome should be recorded on the AE page/screen of the eCRF.  If the abnormality was not 
a part of a diagnosis or syndrome, then the laboratory abnormality should be recorded as the AE. 
If possible, the laboratory abnormality should be recorded as a medical term and not simply as an 
abnormal laboratory result (eg, record thrombocytopenia rather than decreased platelets).
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10.4
Pregnancy
All pregnancies or suspected pregnancies occurring in either a female subject of childbearing 
potential or partner of childbearing potential of a male subject are immediately reportable events. 
In the event of a pregnancy occurring in a female subject of childbearing potential or female partner 
of a male subject, Celgene will follow up with the clinical investigator each trimester of pregnancy 
and for 1 year following the birth of the infant (if applicable). Please reference the pregnancy 
information consent (permission) forms for data collection for additional information. 
The exposure of any pregnant female (eg, caregiver, pharmacist, study coordinator or monitor) to 
CC-90009 is also an immediately reportable event.
10.4.1
Females of Childbearing Potential:
Pregnancies and suspected pregnancies (including elevated β-hCG or positive pregnancy test in a 
female subject of childbearing potential regardless of disease state) occurring while the subject is 
on CC-90009, or within 28 days of the subject’s last dose of CC-90009, are considered 
immediately reportable events.  Investigational product is to be discontinued immediately. The 
pregnancy, suspected pregnancy, or positive pregnancy test must be reported to Celgene Drug 
Safety immediately by email, phone or facsimile, or other appropriate method, using the Pregnancy 
Initial Report Form, or approved equivalent form.
The female subject should be referred to an obstetrician-gynecologist, preferably one experienced 
in reproductive toxicity for further evaluation and counseling.  The Investigator will follow the 
female subject until completion of the pregnancy, and must notify Celgene Drug Safety 
immediately about the outcome of the pregnancy (either normal or abnormal outcome) using the 
Pregnancy Follow-up Report Form, or approved equivalent form.
If the outcome of the pregnancy was abnormal (eg, spontaneous abortion), the Investigator should 
report the abnormal outcome as an AE.  If the abnormal outcome meets any of the serious criteria, 
it must be reported as an SAE to Celgene Drug Safety by facsimile, or other appropriate method, 
within 24 hours of the Investigator’s knowledge of the event using the SAE Report Form, or 
approved equivalent form.
All neonatal deaths that occur within 28 days of birth should be reported, without regard to 
causality, as SAEs.  In addition, any infant death after 28 days that the Investigator suspects is 
related to the in utero exposure to the CC-90009 should also be reported to Celgene Drug Safety 
by facsimile, or other appropriate method, within 24 hours of the Investigator’s knowledge of the 
event using the SAE Report Form, or approved equivalent form.
10.4.2
Male Subjects
If a female partner of a male subject taking CC-90009 becomes pregnant, the male subject taking 
CC-90009 should notify the Investigator, and the pregnant female partner should be advised to call 
their healthcare provider immediately.  Where applicable, the CC-90009 may need to be 
discontinued in the male subject, but may be resumed later at the discretion of the Investigator and 
medical monitor.
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10.5
Reporting of Serious Adverse Events
Any AE that meets any serious criterion requires reporting as an SAE within 24 hours of the 
Investigator’s knowledge of the event.  This instruction pertains to initial SAE reports as well as
any follow-up reports.
This requirement applies to all SAEs (regardless of relationship to CC-90009) that occur during 
the study (from the time the subject signs informed consent until 28 days after the last dose of CC-
90009) or any SAE made known to the Investigator at any time thereafter that are suspected of 
being related to CC-90009.  Serious adverse events occurring prior to treatment (after signing the 
ICD) are to be recorded within the CRF, but do not require reporting to Celgene Drug Safety.
The SAE is reported directly to Celgene Drug Safety by facsimile, or other appropriate method 
using the SAE Report Form or approved equivalent form. The SAE report should provide a 
detailed description of the SAE and include a concise summary of hospital records and other 
relevant documents.  If a subject died and an autopsy has been performed, results of the autopsy 
report and/or death certificate are to be reported to Celgene Drug Safety as soon as these become 
available.  Any follow-up data, including responses to safety queries, should be detailed in a 
subsequent SAE Report Form, or approved equivalent form, and sent to Celgene Drug Safety. 
Queries pertaining to SAEs will be communicated from Celgene Drug Safety to the site via 
facsimile or electronic mail. Urgent queries (eg, missing causality assessment) may be handled by 
phone.
Where required by local legislation, the Investigator is responsible for informing the Institutional 
Review Board/Ethics Committee (IRB/EC) of the SAE and providing them with all relevant initial 
and follow-up information about the event. The Investigator must keep copies of all SAE 
information on file including correspondence with Celgene and the IRB/EC.
10.6
Expedited Reporting of Adverse Events
For the purpose of regulatory reporting, Celgene Drug Safety will determine the expectedness of 
events suspected of being related to CC-90009 based on the Investigator Brochure.
In the United States, expedited reports sent to the FDA by the sponsor based on the reasonable 
possibility threshold are known as ‘IND safety reports’ and will be reported in accordance with 21 
CFR 312.32.
For reporting to the FDA, events that are not suspected to be causally related to CC-90009 by the 
sponsor will not be considered adverse reactions. As per FDA regulations, events that are 
anticipated in the study population (refer to Section 7.2.13 and the CC-90009 Investigator’s 
Brochure Section 6.3.8 Reference Safety Information) will not be considered adverse reactions on 
individual assessment and will be reviewed on an aggregate basis for assessment of frequency.
For countries within the European Economic Area (EEA), Celgene or its authorized representative 
will report in an expedited manner to Regulatory Authorities and Ethics Committees concerned, 
suspected unexpected serious adverse reactions (SUSARs) in accordance with Directive 
2001/20/EC and the Detailed Guidance on collection, verification and presentation of adverse 
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reaction reports arising from clinical trials on investigational products for human use (ENTR/CT3) 
and also in accordance with country-specific requirements.
Celgene or its authorized representative shall notify the Investigator of the following information:

Any AE suspected of being related to the use of CC-90009 in this study or in other studies that 
is both serious and unexpected (eg, SUSAR);

Any finding from tests in laboratory animals that suggests a significant risk for human subjects 
including reports of mutagenicity, teratogenicity, or carcinogenicity.
Where required by local legislation, the Investigator shall notify his/her IRB/EC promptly of these 
new serious and unexpected AE(s) or significant risks to subjects.
The Investigator must keep copies of all pertinent safety information on file including 
correspondence with Celgene and the IRB/EC.  (See Section 14.3 for record retention 
information).
Celgene Drug Safety Contact Information:
For Celgene Drug Safety contact information, please refer to the Serious Adverse Event Report 
Form Completion Guidelines or to the Pregnancy Report Form Completion Guidelines.
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11
DISCONTINUATIONS
11.1
Treatment Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the 
investigational product:

Adverse Event

Withdrawal by subject

Treatment failure

Physician decision

Protocol violation

Progressive disease

Death

Lost to follow-up

Pregnancy

Lack of efficacy

Other (to be specified on the eCRF)
The reason for discontinuation of treatment should be recorded in the eCRF and in the source 
documents.
The decision to discontinue a subject from treatment remains the responsibility of the treating 
physician, which will not be delayed or refused by the Sponsor.  Subjects with progressive disease 
who, in the opinion of the Investigator, are deriving clinical benefit may remain on study after 
discussion with the Medical Monitor. However, prior to discontinuing a subject, the Investigator 
may contact the Medical Monitor and forward appropriate supporting documents for review and 
discussion.
11.2
Study Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the study:

Screen failure

Withdrawal by subject

Physician decision

Protocol violation

Death

Lost to follow-up

Other (to be specified on the eCRF)
The reason for study discontinuation should be recorded in the eCRF and in the source documents.
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12
EMERGENCY PROCEDURES
12.1
Emergency Contact
In emergency situations, the Investigator should contact the responsible Clinical Research 
Physician/Medical Monitor or designee by telephone at the number(s) listed on the Emergency 
Contact Information page of the protocol (after title page).
In the unlikely event that the Clinical Research Physician/Medical Monitor or designee cannot be 
reached, please contact the global Emergency Call Center by telephone at the number listed on the 
Emergency Contact Information page of the protocol (after title page). This global Emergency Call 
Center is available 24 hours a day and 7 days a week. The representatives are responsible for 
obtaining your call-back information and contacting the on-call Celgene/contract research 
organization Medical Monitor, who will then contact you promptly.
Note: The back-up 24-hour global emergency contact call center should only be used if you are 
not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for emergency 
calls. 
12.2
Emergency Identification of Investigational Products
This is an open-label study; therefore, CC-90009 will be identified on the package labeling.
Subjects enrolled in this study will be issued an identification card showing the name of this study 
and an emergency contact number.  This can be used by health care professionals seeking 
emergency information about a subject’s participation in the study.
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13
REGULATORY CONSIDERATIONS
13.1
Good Clinical Practice
The procedures set out in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study are designed to ensure that Celgene, its authorized representative, and 
Investigator abide by GCP, as described in ICH Guideline E6 and in accordance with the general 
ethical principles outlined in the Declaration of Helsinki. The study will receive approval from an 
IRB/EC prior to commencement. The Investigator will conduct all aspects of this study in 
accordance with applicable national, state, and local laws of the pertinent regulatory authorities.
13.2
Investigator Responsibilities
Investigator responsibilities are set out in the ICH Guideline for GCP and in the local regulations.  
Celgene staff or an authorized representative will evaluate and approve all Investigators who in 
turn will select their staff.
The Investigator should ensure that all persons assisting with the study are adequately informed 
about the protocol, amendments, study treatments, as well as study-related duties and functions, 
including obligations of confidentiality of Celgene information. The Investigator should maintain 
a list of Sub-investigators and other appropriately qualified persons to whom he or she has 
delegated significant study-related duties.
The Investigator is responsible for keeping a record of all subjects who sign an informed consent 
form (ICF) and are screened for entry into the study.  Subjects who fail screening must have the 
reason(s) recorded in the subject’s source documents.
The Investigator, or a designated member of the Investigator’s staff, must be available during 
monitoring visits to review data, resolve queries and allow direct access to subject records 
(eg, medical records, office charts, hospital charts, and study-related charts) for source data 
verification.  The Investigator must ensure timely and accurate completion of eCRFs and queries.
The information contained in the protocol and amendments (with the exception of the information 
provided by Celgene on public registry websites) is considered Celgene confidential information.  
Only information that is previously disclosed by Celgene on a public registry website may be 
freely disclosed by the Investigator or its institution, or as outlined in the Clinical Trial Agreement.  
Celgene protocol, amendment and IB information is not to be made publicly available (for example 
on the Investigator’s or their institution’s website) without express written approval from Celgene.  
Information proposed for posting on the Investigator’s or their institution’s website must be 
submitted to Celgene for review and approval, providing at least 5 business days for review.
At the time results of this study are made available to the public, Celgene will provide Investigators 
with a summary of the results that is written for the lay person. The Investigator is responsible for 
sharing these results with the subject and/or their caregiver as agreed by the subject.
13.3
Subject Information and Informed Consent
The Investigator must obtain informed consent of a subject and/or a subject’s legal representative 
prior to any study related procedures.
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Documentation that informed consent occurred prior to the study subject’s entry into the study and 
of the informed consent process should be recorded in the study subject’s source documents 
including the date.  The original ICF signed and dated by the study subject and by the person 
consenting the study subject prior to the study subject’s entry into the study, must be maintained 
in the Investigator’s study files and a copy given to the study subject.  In addition, if a protocol is 
amended and it impacts on the content of the informed consent, the ICF must be revised.  Study 
subjects participating in the study when the amended protocol is implemented must be re-
consented with the revised version of the ICF.  The revised ICF signed and dated by the study 
subject and by the person consenting the study subject must be maintained in the Investigator’s 
study files and a copy given to the study subject.
13.4
Confidentiality
Celgene affirms the subject’s right to protection against invasion of privacy and to be in 
compliance with ICH and other local regulations (whichever is most stringent). Celgene requires 
the Investigator to permit Celgene’s representatives and, when necessary, representatives from 
regulatory authorities, to review and/or copy any medical records relevant to the study in 
accordance with local laws.
Should direct access to medical records require a waiver or authorization separate from the 
subject’s signed ICF, it is the responsibility of the Investigator to obtain such permission in writing 
from the appropriate individual.
13.5
Protocol Amendments
Any amendment to this protocol must be approved by the Celgene Clinical Research 
Physician/Medical Monitor.  Amendments will be submitted to the IRB/EC for written approval.  
Written approval must be obtained before implementation of the amended version occurs.  The 
written signed approval from the IRB/EC should specifically reference the Investigator name, 
protocol number, study title and amendment number(s) that is applicable. Amendments that are 
administrative in nature do not require IRB/IEC approval but will be submitted to the IRB/IEC for 
information purposes.
13.6
Institutional Review Board/Independent Ethics Committee Review and 
Approval
Before the start of the study, the study protocol, ICF, and any other appropriate documents will be 
submitted to the IRB/EC with a cover letter or a form listing the documents submitted, their dates 
of issue, and the site (or region or area of jurisdiction, as applicable) for which approval is sought. 
If applicable, the documents will also be submitted to the authorities in accordance with local legal 
requirements.
IP can only be supplied to an Investigator by Celgene or its authorized representative after 
documentation on all ethical and legal requirements for starting the study has been received by 
Celgene or its authorized representative. This documentation must also include a list of the 
members of the IRB/EC and their occupation and qualifications. If the IRB/EC will not disclose 
the names, occupations and qualifications of the committee members, it should be asked to issue 
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a statement confirming that the composition of the committee is in accordance with GCP. For 
example, the IRB General Assurance Number may be accepted as a substitute for this list. Formal 
approval by the IRB/EC should mention the protocol title, number, amendment number (if 
applicable), study site (or region or area of jurisdiction, as applicable), and any other documents 
reviewed. It must mention the date on which the decision was made and must be officially signed 
by a committee member. Before the first subject is enrolled in the study, all ethical and legal 
requirements must be met.
The IRB/EC and, if applicable, the authorities, must be informed of all subsequent protocol 
amendments in accordance with local legal requirements. Amendments must be evaluated to 
determine whether formal approval must be sought and whether the ICF should also be revised.
The Investigator must keep a record of all communication with the IRB/EC and, if applicable, 
between a Coordinating Investigator and the IRB/EC. This statement also applies to any 
communication between the Investigator (or Coordinating Investigator, if applicable) and 
regulatory authorities.
Any advertisements used to recruit subjects for the study must be reviewed by Celgene and the 
IRB/EC prior to use.  
13.7
Ongoing Information for Institutional Review Board/ Ethics Committee
If required by legislation or the IRB/EC, the Investigator must submit to the IRB/EC:

Information on serious or unexpected adverse events as soon as possible; 

Periodic reports on the progress of the study;

Deviations from the protocol or anything that may involve added risk to subjects.
13.8
Termination of the Study
Celgene reserves the right to terminate this study prematurely at any time for reasonable medical 
or administrative reasons. Any premature discontinuation will be appropriately documented 
according to local requirements (eg, IRB/EC, regulatory authorities, etc).
In addition, the Investigator or Celgene has the right to discontinue a single site at any time during 
the study for medical or administrative reasons such as:

Unsatisfactory enrollment;

GCP noncompliance;

Inaccurate or incomplete data collection;

Falsification of records;

Failure to adhere to the study protocol.
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14
DATA HANDLING AND RECORDKEEPING 
14.1
Data/Documents
The Investigator must ensure that the records and documents pertaining to the conduct of the study 
and the distribution of the investigational product are complete, accurate, filed and retained.  
Examples of source documents include: hospital records; clinic and office charts; laboratory notes; 
memoranda; subject’s diaries or evaluation checklists; dispensing records; recorded data from 
automated instruments; copies or transcriptions certified after verification as being accurate copies; 
microfiche; x-ray film and reports; and records kept at the pharmacy, and the laboratories, as well 
as copies of eCRFs or CD-ROM.
14.2
Data Management
Data will be collected via eCRF and entered into the clinical database per Celgene SOPs. This data 
will be electronically verified through use of programmed edit checks specified by the clinical 
team.  Discrepancies in the data will be brought to the attention of the clinical team, and 
investigational site personnel, if necessary.  Resolutions to these issues will be reflected in the 
database.  An audit trail within the system will track all changes made to the data.
14.3
Record Retention
Essential documents must be retained by the Investigator according to the period of time outlined 
in the clinical trial agreement. The Investigator must retain these documents for the time period 
described above or according to local laws or requirements, whichever is longer. Essential 
documents include, but are not limited to, the following:

Signed ICFs for all subjects;

Subject identification code list, screening log (if applicable), and enrollment log;

Record of all communications between the Investigator and the IRB/EC;

Composition of the IRB/EC;

Record of all communications between the Investigator, Celgene, and their authorized 
representative(s);

List of Sub-investigators and other appropriately qualified persons to whom the Investigator 
has delegated significant study-related duties, together with their roles in the study, curriculum 
vitae, and their signatures;

Copies of CRFs (if paper) and of documentation of corrections for all subjects;

CC-90009 accountability records;

Record of any body fluids or tissue samples retained;

All other source documents (subject records, hospital records, laboratory records, etc.); 

All other documents as listed in Section 8 of the ICH consolidated guideline on GCP (Essential 
Documents for the Conduct of a Clinical Trial).
The Investigator must notify Celgene if he/she wishes to assign the essential documents to 
someone else, remove them to another location or is unable to retain them for a specified period.  
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The Investigator must obtain approval in writing from Celgene prior to destruction of any records. 
If the Investigator is unable to meet this obligation, the Investigator must ask Celgene for 
permission to make alternative arrangements. Details of these arrangements should be 
documented. 
All study documents should be made available if required by relevant health authorities. 
Investigator or institution should take measures to prevent accidental or premature destruction of 
these documents.
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15
QUALITY CONTROL AND QUALITY ASSURANCE
All aspects of the study will be carefully monitored by Celgene or its authorized representative for 
compliance with applicable government regulations with respect to current GCP and SOPs.
15.1
Study Monitoring and Source Data Verification
Celgene ensures that appropriate monitoring procedures are performed before, during and after the 
study.  All aspects of the study are reviewed with the Investigator and the staff at a study initiation 
visit and/or at an Investigators’ Meeting.  Prior to enrolling subjects into the study, a Celgene 
representative will review the protocol, eCRFs, procedures for obtaining informed consent, record 
keeping, and reporting of AEs/SAEs with the Investigator.
Monitoring details describing strategy, including definition of study critical data items and 
processes (eg, risk-based initiatives in operations and quality such as risk management and 
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques (central, 
remote, or on-site monitoring) are provided in the monitoring plan.
Accuracy will be checked by performing source data verification that is a direct comparison of the 
entries made onto the eCRFs against the appropriate source documentation.  Any resulting 
discrepancies will be reviewed with the Investigator and/or his/her staff.  Any necessary 
corrections will be made directly to the eCRFs or via queries by the Investigator and/or his/her 
staff. Monitoring procedures require that informed consents, adherence to inclusion/exclusion 
criteria and documentation of SAEs and their proper recording be verified.  Additional monitoring 
activities may be outlined in a study-specific monitoring plan.
15.2
Audits and Inspections
In addition to the routine monitoring procedures, a Good Clinical Practice Quality Assurance unit 
exists within Celgene.  Representatives of this unit will conduct audits of clinical research activities 
in accordance with Celgene SOPs to evaluate compliance with Good Clinical Practice guidelines 
and regulations.
The Investigator is required to permit direct access to the facilities where the study took place, 
source documents, eCRFs and applicable supporting records of study subject participation for 
audits and inspections by IRB/ECs, regulatory authorities (eg, FDA, EMA, Health Canada) and 
company authorized representatives.  The Investigator should make every effort to be available for 
the audits and/or inspections.  If the Investigator is contacted by any regulatory authority regarding 
an inspection, he/she should contact Celgene immediately.
15.3
Investigational Medicinal Product Quality Issues
Issues that call into question IP safety, purity, potency, quality and identity (eg, evidence of 
suspected tampering of product) must be reported as soon as possible to the study Clinical Trial 
Monitor and/or Clinical Trial Manager or designee. Report an issue or concern with all sponsor 
supplied IP suspected to have occurred before the product was transferred to the responsibility of 
the investigational site (eg, during manufacturing, packaging and labeling, storage, and/or 
distribution).
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This includes suspected quality issues of components co-packaged with the drug, labelling, and IP 
device/drug combination products, and medical devices. 
In the event of a suspected product quality issue, the immediate action to be taken by site is to 
quarantine the affected product. Do not dispose of the product unless retention presents a risk to 
personnel (eg, cytotoxic, risk of injury from broken glass or sharps).
When reporting, provide as much product information as possible. Suspected IP quality issues will 
be investigated and a response will be provided back to the investigational site.
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16
PUBLICATIONS
As described in Section 13.2, all protocol- and amendment-related information, with the exception 
of the information provided by Celgene on public registry websites, is considered Celgene 
confidential information and is not to be used in any publications.  Celgene protocol-related 
information proposed for use in a publication must be submitted to Celgene for review and 
approval, and should not be utilized in a publication without express written approval from 
Celgene, or as described in the Clinical Trial Agreement.  
Celgene will ensure Celgene-sponsored studies are considered for publication in the scientific 
literature in a peer-reviewed journal, irrespective of the results.  At a minimum, this applies to 
results from all Phase 3 clinical studies, and any other study results of significant medical 
importance.  This also includes results relating to investigational medicines whose development 
programs have been discontinued.
Study results may also be presented at one or more medical congresses, and may be used for 
scientific exchange and teaching purposes.  Additionally, this study and its results may be 
submitted for inclusion in all appropriate health authority study registries, as well as publication 
on health authority study registry websites, as required by local health authority regulations.  
Eligibility for external authorship, as well as selection of first authorship, will be based on several 
considerations, including, but not limited to, contribution to protocol development, study 
recruitment, data quality, participation in data analysis, participation in study steering committee 
(when applicable) and contribution to abstract, presentation and/or publication development.
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17
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recommendations of the International Working Group for diagnosis, standardization of response 
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azacitidine compared with that of conventional care regimens in the treatment of higher-risk 
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Klein, JP, Moeschberger ML. Nonparametric estimation of basic quantities for right-censored and 
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Kurzrock R.  Myelodysplastic syndrome overview.  Semin Hematol 2002;39(3 Suppl 2):18-25.
Lee DW, Gardner R, Porter DL, Louis CJ, Ahmed N, Jensen M, et al. Current concepts in the 
diagnosis and management of cytokine release syndrome. Blood:124(2): 188-195.
Lee SH, Erber WN, Porwit A, Tomonaga M, Peterson LC. ICSH guidelines for the standardization 
of bone marrow specimens and reports. Int Jnl Lab Hem 2008;30:349-364.
Leith CP, Kopecky KJ, Godwin J, McConnell T, Slovak ML, et al. Acute myeloid leukemia in the 
elderly: assessment of multidrug resistance (MDR1) and cytogenetics distinguishes biologic 
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Storer BE. Design and analysis of phase I clinical trials. Biometrics. 1989;45(3):925–937.
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18
APPENDICES
Appendix A:
Table of Abbreviations
Table 16:
Abbreviations and Specialist Terms
Abbreviation or 
Specialist Term
Explanation
AC
Before meals
ADL
Activity of daily life
AE
Adverse event
ALT
Alanine aminotransferase (SGPT)
AML
Acute myeloid leukemia
ANC
Absolute neutrophil count
AST
Aspartate aminotransferase (SGOT)
AUC
Area under the plasma concentration-time curve
AUCt
AUC calculated to the last observable concentration at time t 
β-CTx
β-C-terminal telopeptide 
β-hCG
β-subunit of human chorionic gonadotropin
BID
Two times a day
BUN
Blood urea nitrogen
C
Cycle
C5min
Plasma concentration at 5 minutes
Ca
Calcium
CBC
Complete blood count
CD
Cluster of differentiation
CEBPα
CCAAT/enhancer binding protein alpha
CHO
Chinese hamster ovary
CI
Confidence interval
CL
Clearance
Cmax
Maximum observed concentration of drug
CNS
Central nervous system
CO2
Carbon dioxide
CR
Complete remission
CRBN
Cereblon
CRc
Cytogenetic complete remission
CRF
Case report form
CRh
Morphologic CR with partial hematologic recovery
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Table 16:
Abbreviations and Specialist Terms
Abbreviation or 
Specialist Term
Explanation
CRi
Morphologic CR with incomplete blood recovery
CRL
Cullin ring ligase
CRm
molecular CR
CRR
Complete remission rate
CTCAE
Common Terminology Criteria for Adverse Events
CV%
Coefficient of variation
CYP
Cytochrome P450
D
Day
DLT
Dose-limiting toxicity
DMA
N,N,-Dimethylacetamide
EC
Ethics Committee
ECG
Electrocardiogram
ECHO
Echocardiogram
ECOG PS
Eastern Cooperative Oncology Group Performance Status
eCRF
Electronic case report form
EEA
European Economic Area
EFS
Event-free survival
Emax
Maximum possible effect
EMD
Extra medullary disease
EOI
End of injection
EOT
End of treatment
FCBP
Females of child bearing potential
FDA
Food and Drug Administration
FISH
Fluorescence in situ hybridization
FLT3
Fms-related tyrosine kinase 3
G6PD
Glucose-6-phosphate dehydrogenase
GCP
Good Clinical Practice
G-CSF
Granulocyte-colony stimulating factor 
GLP
Good Laboratory Practice
GVHD
Graft-versus-host disease
HBV
Hepatitis B virus
HCV
Hepatitis C virus
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Table 16:
Abbreviations and Specialist Terms
Abbreviation or 
Specialist Term
Explanation
HED
Human equivalent dose
HPBCD
Hydroxypropyl beta-cyclodextrin 
HIV
Human immunodeficiency virus
HMA
Hypomethylating agent
HNSTD
Highest non-severely toxic dose
HR MDS
Higher-risk myelodysplastic syndromes
HPB
Hydroxypropyl beta-cyclodextrin
HSCT
Hematopoietic stem cell transplant
IC50
Half maximal inhibitory concentration
ICD
Informed consent document
ICF
Informed consent form
ICH
International Council for Harmonisation
ICSH
International Council for Standardization in Hematology 
IgG
Immunoglobulin G
ImiD
Immunomodulatory drug
IND
Investigational New Drug
INR
International normalized ratio
IP
Investigational Product
IPSS-R
Revised International Prognostic Scoring System score
IRB
Institutional Review Board
IRT
Integrated Response Technology
IV
Intravenous
IWG
International working group
KIT
Stem cell factor receptor
LDH
Lactate dehydrogenase
LSU
Limited stay unit
LVEF
Left ventricular ejection fraction
mCR
Marrow complete remission
MDS
Myelodysplastic syndromes
MedDRA
Medical Dictionary for Regulatory Activities
MLFS
Morphologic leukemia-free state
Mg
Magnesium
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Table 16:
Abbreviations and Specialist Terms
Abbreviation or 
Specialist Term
Explanation
MRC
Medical research council
MRD
Minimal residual disease
mRNA
Messenger RNA
MTD
Maximum tolerated dose
MUGA
Multi-gated acquisition
N
Number
NCI
National Cancer Institute
NMD
Nonsense-mediated decay
NOAEL
No observed adverse effect level
NOEL
No observable effect level
NPM1
Nucleophosmin 1
NTD
Non-tolerated dose
O2
Oxygen
ORR
Objective response rate
OS
Overall survival
P1NP
Procollagen type 1 N-terminal propeptide
PBMC
Peripheral blood mononuclear cells
PD
Pharmacodynamic or disease progression
PFS
Progression-free survival
PK
Pharmacokinetics
PO
By mouth
PPI
Proton pump inhibitor
PPP
Pregnancy prevention plan
PR
Partial remission
PT
Prothrombin time
PTH
Parathyroid hormone
PTT
Partial thromboplastin time
Q
Every
QD
Once a day
RFS
Relapse-free survival
RP2D
Recommended Phase 2 Dose
R/R
Relapsed or refractory
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Table 16:
Abbreviations and Specialist Terms
Abbreviation or 
Specialist Term
Explanation
RT-PCR
Reverse transcription-polymerase chain reaction
SAE
Serious adverse event
SAP
Statistical analysis plan
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
SD
Standard deviation
SE
Standard error
SGOT
Serum glutamic oxaloacetic transaminase 
SGPT
Serum glutamic pyruvic transaminase
SOP
Standard operating procedure
SRC
Safety review committee
STD
Severely toxic dose
STD10
Severely toxic dose in 10%
SUSAR
Suspected unexpected serious adverse reaction
t1/2
Terminal half-life
tmax
Time to peak plasma concentration
T4
Thyroxine
TEAE
Treatment-emergent adverse event
TEASAE
Treatment-emergent serious adverse event
TID
Three times a day
TK
Toxicokinetics
TLS
Tumor lysis syndrome
TSH
Thyroid-stimulating hormone
TTR
Time to remission/response
TTT
Time to transformation
ULN
Upper limit of normal
UPR
Unfolded protein response
US
United States 
USP
US Pharmacopeia
Vss
Volume of distribution
WBC
White blood cell count
WK
Week
WNL
Within normal limits
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Appendix B:
The World Health Organization (WHO) Classification of Acute 
Myeloid Leukemia (AML)
Table 17:
WHO classification of AML
AML with recurrent genetic abnormalities
AML with t(8;21)(q22;q22.1);RUNX1-RUNX1T1
AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22);CBFB-MYH11
APL with PML-RARA
AML with t(9;11)(p21.3;q23.3);KMT2A-MLLT3
AML with t(6;9)(p23;q34.1);DEK-NUP214
AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOM
AML (megakaryoblastic) with t(1;22)(p13.3;q13.3);RBM15-MKL1
Provisional entity: AML with BCR-ABL1
AML with mutated NPM1
AML with biallelic mutations of CEBPA
Provisional entity: AML with mutated RUNX1
AML with myelodysplasia-related changes
Therapy-related myeloid neoplasms
AML, NOS
AML with minimal differentiation
AML without maturation
AML with maturation
Acute myelomonocytic leukemia
Acute monoblastic/monocytic leukemia
Pure erythroid leukemia
Acute megakaryoblastic leukemia
Acute basophilic leukemia
Acute panmyelosis with myelofibrosis
AML = acute myelogenous leukemia; NOS = not otherwise specified.
Source: Arber, 2016.
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Appendix C:
Response Criteria for Acute Myeloid Leukemia 
The revised recommendations of the International Working Group for diagnosis, standardization 
of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute 
myeloid leukemia (Cheson, 2003).
Table 18:
Hematologic Response According to IWG Criteria for AML
Response Criterion
Time of Assessment
Neutrophils 
(µL)
Platelets 
(µL)
Bone 
Marrow 
Blasts (%)
Other
Early Treatment assessment 
7-10 days after therapy
NA
NA
< 5
Morphologic Leukemia-free 
State 
Varies by protocol 
NA
NA
< 5
Flow cytometry 
EMD 
Morphologic CR 
Varies by protocol 
≥1,000
≥100,000
< 5
Transfusion EMD 
Cytogenetic CR (CRc) 
Varies by protocol 
≥ 1,000
≥100,000
< 5
Cytogenetics—
normal, EMD 
Molecular CR (CRm)
Varies by protocol 
≥ 1,000
≥100,000
< 5
Molecular—negative, 
EMD 
Morphologic CR with 
incomplete blood recovery 
(CRi)
Varies by protocol
Fulfill all criteria for CR except for residual neutropenia 
(< 1,000/µL) or thrombocytopenia (< 100,000/µL).
Morphologic CR with partial 
hematologic recovery (CRh)
Per protocol
>500
>50,000
< 5
Partial Remission 
Varies by protocol 
≥1,000
≥100,000
Decrease 
≥50 resulting 
in 5 to 25
Blasts ≤5% if Auer 
rod positive 
Relapse after CR 
Varies by protocol
Reappearance of leukemic blasts in the peripheral blood or ≥ 5% 
blasts in the bone marrow not attributable to any other cause (eg, 
bone marrow regeneration after consolidation therapy).
AML = acute myelogenous leukemia; CR = complete remission; EMD = extramedullary disease; IWG = International Working 
Group; NA = not applicable.
Source: Cheson, 2003, Bloomfield, 2018.
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Appendix D:
Performance Status Criteria
Table 19:
Eastern Cooperative Oncology Group (ECOG) Performance Status 
(PS)
Score
Description
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a 
light or sedentary nature, eg, light housework, office work.
2
Ambulatory and capable of all self-care but unable to carry out any work activities.  Up and 
about more than 50% of waking hours.
3
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
4
Completely disabled.  Cannot carry on any self-care.  Totally confined to bed or chair
5
Dead
Source: Oken, 1982.
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Appendix E:
The World Health Organization (WHO) Classification of the 
Myelodysplastic Syndromes
Table 20:
WHO classifications for MDS
WHO myeloid neoplasm and acute 
leukemia classification
Dysplastic 
findings
Cytopeniasa
PB and BM findings and cytogenetics
MDS with single lineage dysplasia 
(MDS-SLD)
1
1 or 2
BM <5%, PB <1%, no Auer Rods
Any cytogenetics, unless fulfills all 
criteria for MDS with isolated del(5q)
MDS with ring sideroblasts (MDS-RS)b
    MDS-RS and single lineage dysplasia
    MDS-RS and multilineage dysplasia
1
2 or 3
1 or 2
3
BM <5%, PB <1%, no Auer Rods
Any cytogenetics, unless fulfills all 
criteria for MDS with isolated del(5q)
MDS with multilineage dysplasia (MDS-
MLD)
2 or 3
1-3
BM <5%, PB <1%, no Auer Rods
Any cytogenetics, unless fulfills all 
criteria for MDS with isolated del(5q)
MDS with excess blasts (MDS-EB)
     MDS-EB-1
0-3
1-3
BM 5-9% or PB 2-4%, no Auer Rods
Any cytogenetics
     MDS-EB-2
0-3
1-3
BM 10-19% or PB 5-19% or Auer 
Rods
Any cytogenetics
MDS with isolated del(5q)
1-3
1-2
BM <5%, PB <1%, no Auer Rods
del(5q) alone or with 1 additional 
abnormality except -7 or del(7q)
MDS, unclassifiable (MDS-U)
    MDS-U with 1% blood blasts
1-3
1-3
BM <5%, PB =1%c, no Auer Rods
Any cytogenetics
    MDS-U with SLD and pancytopenia
1
3
BM <5%, PB <1%, no Auer Rods
Any cytogenetics
    MDS-U based on defining cytogenetic 
abnormality
0
1-3
BM <5%, PB <1%, no Auer Rods
MDS-defining abnormalityd
a Cytopenias defined as : hemoglobin, <10 g/dL, platelet count, <100 x 109/L; and absolute neutrophil count, <1.8 x 
109/L. Rarely, MDS may present with mild anemia or thrombocytopenia above these levels. Peripheral blood 
monocytes must be < 1 x 109/L.
b Cases with ≥ 15% ring sideroblasts by definition have significant erythroid dysplasia, and are classified as MDS-
RS-SLD.
c One percent PB blasts must be recorded on at least 2 separate occasions.
d Abnormality must be demonstrated by conventional karyotyping, not by FISH or sequencing. The presence of +8, 
-Y, of del(20q) is not considered to be MDS-defining in the absence of diagnostic morphologic features of MDS.
Sources: Arber, 2016 and Vardiman, 2009.
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Appendix F:
International Working Group (IWG) Response Criteria for 
Myelodysplasia
Table 21:
Modified IWG Response Criteria for MDS
Category
Response criteria (responses must last at least 4 weeks)
Complete remission (CR)
Bone marrow:  ≤ 5% myeloblasts with normal maturation of all cell linesa
Persistent dysplasia will be noteda,b
Peripheral bloodc
-
Hemoglobin ≥ 11 g/dL
-
Platelets ≥ 100 × 109/L
-
Neutrophils ≥ 1.0 × 109/Lb
-
Blasts 0%
Partial remission (PR)
All CR criteria if abnormal before treatment, except:
Bone marrow blasts decreased by ≥ 50% over pretreatment but still > 5%
Cellularity and morphology not relevant
Marrow CRb
± Hematologic Improvement 
(HI)
Bone marrow:  ≤ 5% myeloblasts and decrease by ≥ 50% over pretreatmentb
Note: Blasts at baseline must be ≥ 5% in order for subject to be evaluable for 
Marrow CRd
Peripheral blood: if HI responses, they will be noted in addition to marrow CRb
Stable disease (SD)
Failure to achieve at least PR, but no evidence of progression for > 8 weeks
Failure
Death during treatment or disease progression characterized by worsening of 
cytopenias, increase in percentage of bone marrow blasts, or progression to a 
more advanced MDS FAB subtype than pretreatment
Relapse after CR or PR
At least 1 of the following:

Return to pretreatment bone marrow blast percentage

Decrement of ≥50% from maximum remission/response levels in 
granulocytes or platelets

Reduction of Hgb concentration by ≥ 1.5 g/dL or transfusion dependence
Cytogenetic Response
Complete – Disappearance of the chromosomal abnormality without 
appearance of new ones
Partial – At least 50% reduction of the chromosomal abnormality
Disease Progression (PD)
For patients with:
Less than 5% blasts: ≥ 50% increase in blasts to > 5% blasts
5% - 10% blasts: ≥ 50% increase in blasts to > 10% blasts
10% - 20% blasts: ≥ 50% increase in blasts to > 20% blasts
Any of the following:
At least 50% decrement from maximum remission/response levels in 
granulocytes or platelets
Reduction in Hgb concentration by ≥ 2 g/dL 
Transfusion dependence
Disease transformation
Transformation to AML (20% or more BM or PB blasts)d
Hematologic Improvement (HI)
    Erythroid response (HI-E)
   (Pretreatment < 11 g/dL)
Hgb increase by ≥ 1.5 g/dL
Relevant reduction of units of RBC transfusions by an absolute number of at 
least 4 RBC transfusions/8 weeks compared with the pretreatment transfusion 
number in the previous 8 weeks. Only RBC transfusions given for a Hgb of ≤ 
9.0 g/dL pretreatment will count in the RBC transfusion evaluation
    Platelet response (HI-P)
   (Pretreatment < 100 × 109/L)
Absolute increase of ≥ 30 × 109/L for patients starting with > 20 × 109/L
Increase from < 20 × 109/L to > 20 × 109/L and by at least 100%
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Table 21:
Modified IWG Response Criteria for MDS
Category
Response criteria (responses must last at least 4 weeks)
    Neutrophil response (HI-N)
    (Pretreatment < 1.0 × 109/L)
At least 100% increase and an absolute increase of > 0.5 × 109/L
   Progression/relapse after HI
At least one of the following:
At least 50% decrement from maximum response levels in granulocytes or 
platelets 
Reduction in Hgb by ≥ 1.5 g/dL
Transfusion dependence
BM = bone marrow; CR = complete remission; FAB = French-American-British; Hgb = hemoglobin; HI = 
hematologic improvement; IWG = International Working Group; MDS = myelodysplastic syndromes; PB = 
peripheral blood; PD = Disease Progression; PR = partial remission; RBC = red blood cell.
a Dysplastic changes should consider the normal range of dysplastic changes (modification).
b Modification to IWG response criteria.
c In some circumstances, protocol therapy may require the initiation of further treatment (eg, consolidation, 
maintenance) before the 4-week period. Such subjects can be included in the response category into which they fit 
at the time the therapy is started. Transient cytopenias during repeated chemotherapy courses should not be 
considered as interrupting durability of response, as long as they recover to the improved counts of the previous 
course.
d Sponsor modification of IWG criteria.
Sources: Cheson, 2006 and Vardiman, 2009.
Table 22:
RBC and Platelet Transfusion Independence
At Screening
During Study Treatment
RBC transfusion 
independence
Subjects who received < 4 
RBC units during the 
previous 56 days
Subjects who experienced a Hgb increase of 1.5 g/dL over 
baseline and who received no RBC transfusions during a 
56-day period on treatment.  Note:  Only RBC transfusions 
given for a Hgb of  ≤ 9.0 g/dL within 3 days prior to the 
transfusion will count in the RBC transfusion response 
evaluation
RBC transfusion
dependence
Subjects who received ≥ 4 
RBC units during the 
previous 56 days
Platelet transfusion 
independence
Subjects who received < 2 
platelet transfusions during 
the previous 56 days
Subjects who received no platelet transfusions during a 56-
day period on treatment
Platelet transfusion 
dependence
Subjects who received ≥ 2 
platelet transfusions during 
the previous 56 days.
RBC = red blood cell; Hgb = hemoglobin.
a RBC transfusion independence and RBC transfusion dependence are defined according to modified IWG criteria.
b Platelet transfusion independence and platelet transfusion dependence are defined by the Sponsor.
Source: Cheson, 2006.
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Appendix G:
Revised International Prognostic Scoring System for MDS
Table 23:
IPSS-R Cytogenetic Risk Groups
Cytogenetic Prognostic Subgroups
Cytogenetic Abnormalities
Very good
-Y, del(11q)
Good
Normal, del(5q), del(12p), del(20q), double including del(5q)
Intermediate
del(7q), +8, +19, i(17q), any other single or double independent clones
Poor
-7, inv(3)/t(3q)/del(3q), double including -7/del(7q), Complex: 3 
abnormalities
Very poor
Complex: > 3 abnormalities
Source: Greenburg, 2012.
Table 24:
IPSS-R Prognostic Score Values
Prognostic variable
0
0.5
1
1.5
2
3
4
Cytogenetics
Very 
Good
-
Good
-
Inter-
mediate
Poor
Very 
Poor
Bone Marrow Blast (%)
≤ 2
-
> 2 - < 5
-
5 - 10
> 10
-
Hemoglobin (g/dL)
≥10
-
8 - < 10
<8
-
-
-
Platelets (× 109/L)
≥100
50 - < 100
< 50
-
-
-
-
ANC (× 109/L)
≥0.8
< 0.8
-
-
-
-
-
ANC = absolute neutrophil count.
Source: Greenburg, 2012.
The total IPSS-R score is calculated as the sum of the cytogenetics, bone marrow blast percentage, 
hemoglobin, platelets and ANC individual scores.
Table 25:
IPSS-R Prognostic Risk Categories/Scores
Risk Category
Risk Score
Very Low
≤ 1.5
Low
> 1.5 – 3
Intermediate
> 3 – 4.5
High
> 4.5 – 6
Very High
> 6
Source: Greenburg, 2012.
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Table 26:
IPSS-R: Prognostic Risk Category Clinical Outcomes
Prognostic variable
No. pts
Very Low
Low
Intermediate
High
Very High
Patients, %
7012
19%
38%
20%
13%
10%
Median Overall Survival 
(years)
-
8.8
5.3
3.0
1.6
0.8
Median time to 25% 
AML evolution
-
Not 
reached
10.8
3.2
1.4
0.73
Source: Greenberg, 2012.
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Appendix H:
Risk Status Based on Cytogenetics for Acute Myeloid Leukemia
Table 27:
Risk Groups
Risk Status
Cytogenetics
Molecular Abnormalitiesa
Favorable-risk
Core binding factor: inv(16)b,c,d or
t(16;16)b,c,d or t(8;21)b,d or t(15;17)d
Normal cytogenetics:
NPM1 mutation in the absence of FLT3-
ITD or isolated biallelic CEBPA mutation 
Intermediate-risk
Normal cytogenetics
+8 alone
t(9;11)
Other non-defined
Core binding factor with c-KIT mutationb
Poor-risk
Complex (≥ 3 clonal chromosomal 
abnormalities)
Monosomal karyotype
-5, 5q-, -7, 7q-
11q23 - non t(9;11)
inv(3), t(3;3)
t(6;9)
t(9;22)e
Normal cytogenetics:
with FLT3-ITD mutation f
TP53 mutation
a The molecular abnormalities included in this table reflect those for which validated assays are available in 
standardized commercial laboratories.  Given the rapidly evolving field, risk stratification should be modified based 
on continuous evaluation of research data.  Other novel genetic mutations have been identified that may have 
prognostic significance.  
b Emerging data indicate that the presence of KIT mutations in patients with t(8;21), and to a lesser extent inv(16), 
confers a higher risk of relapse. These patients are considered intermediate risk and should be considered for HSCT 
or clinical trials, if available. Other cytogenetic abnormalities in addition to these finding do not alter risk status.
c Paschka P, Du J, Schlenk RF, Gaidzik VI, Bullinger L, Corbacioglu A, et al. Secondary genetic lesions in acute 
myeloid leukemia with inv(16) or t(16;16): a study of the German-Austrian AML study group (AMLSG). 
Blood 2013; 121:170-177.
d Other cytogenetic abnormalities in addition to these findings do not alter better risk status
e For Philadelphia+ acute myeloid leukemia (AML) t(9;22), manage as myeloid blast crisis in chronic myeloid 
leukemia (CML), with addition of tyrosine kinase inhibitors.  
f FLT3-ITD mutations are considered to confer a significant poorer outcome in subjects with normal karyotype, and 
these subjects should be considered for clinical trials where available.  There is controversy as whether FLT3-TKD 
mutations carry equally poor prognosis
Source: NCCN, 2017a.
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Appendix I:
Tumor Lysis Syndrome Prophylaxis Recommendations
Table 28:
Tumor Lysis Syndrome (TLS) Prophylaxis Recommendations Based 
on TLS Risk
Source:  Cairo, 2010.
Table 29:
Cairo-Bishop Definition of Laboratory Tumor Lysis Syndrome
Uric Acid
≥ 476 μmol/l (≥ 8.0 mg/dl) or 25% increase from baseline
Potassium
≥ 6.0 mmol/l (≥ 6.0 mEq/l) or 25% increase from baseline
Phosphorous
≥ 1.45 mmol/l (≥ 4.5 mg/dl) or 25 % increase from baseline
Calcium
≤ 1.75 mmol/l (≤ 7.0 mg/dl) or 25% decrease from baseline
Source: Cairo, 2004.
Notes:  Laboratory tumor lysis syndrome (LTLS) is defined as either a 25% change or level above or below normal, 
as defined above, for any 2 or more serum values of uric acid, potassium, phosphate, and calcium within 3 days 
before or 7 days after the initiation of chemotherapy.  This assessment assumes that a subject has or will receive 
adequate hydration (± alkalinization) and a hypouricemic agent(s).
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The Cairo-Bishop Definition of Clinical Tumor Lysis Syndrome
The Presence of Laboratory TLS and One or More of the Following Criteria:

Creatinine: ≥ 1.5 upper limit of normal ([ULN] age > 12 years or age-adjusted)

Cardiac arrhythmia / sudden death

Seizure not directly attributable to a therapeutic agent
Table 30:
Cairo-Bishop Grading System for Tumor Lysis Syndrome
Grade
LTLS
Creatinine
Cardiac Arrhythmia
Seizure
0
-
≤ 1.5 x ULN
None
None
1
+
1.5 x ULN
Intervention not indicated
None
2
+
> 1.5 – 3.0 x ULN
Non-urgent medical 
intervention indicated
One brief generalized seizure; 
seizure(s) well controlled by 
anti-convulsants or infrequent; 
focal motor seizures not 
interfering with ADL
3
+
> 3.0 – 6.0 x ULN
Symptomatic and 
incompletely controlled 
medically or controlled with 
device
Seizure in which 
consciousness is altered; 
poorly controlled seizure 
disorder; breakthrough 
generalized seizures despite 
medical intervention
4
+
> 6.0 x ULN
Life-Threatening
Seizures of any kind that are 
prolonged, repetitive, or 
difficult to control
5
+
Deatha
Death
Death
ADL = Activities of Daily Living; LTLS = Laboratory Tumor Lysis Syndrome; ULN = Upper Limit of Normal.
a Probably or definitely attributable to clinical TLS.
Source:  Cairo, 2010.
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Appendix J:
Recommendations for Management of Treatment-Induced 
Diarrhea
The published guidelines (Benson, 2004) were modified to be consistent with the study protocol.  
Source:  Benson, 2004.
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Appendix K:
Part A Table of Events for D1-3/D8-10 Dosing Schedule
Table 31:
Table of Events for Part A (D1-3/D8-10 Schedule) of Cycle 1
Eventsa
Screening
Treatment Period
Cycle 1
WK1
WK2
WK3
WK4
WK5
WK6b
D-28 to -1
D1
D2
D3
D4
D8
D9
D10
D11
D15
D22
D28c
D29
D36
Study Entry (Section 6.1)
Informed consent 
X
Inclusion/ exclusion criteria
X
Medical/ oncologic history 
X
Demographics 
X
IRT registration
X
X
Pregnancy risk counseling and contraceptive 
compliance confirmation
X
As specified in Section 6.1.1 and the PPP in Appendix L.
Prior/ concomitant medications & procedures 
(Section 6.2.1)
X
X
X
X
X
X
X
X
X
X
X
X
X
CC-90009 Administration (Section 7)
Calcium, calcitriol, and vitamin D 
supplements and recording on diary card 
(Section 7.2)
X 
(D-3 to D-1)
X
X
X
X
(D4-7)
X
X
X
Xd
Xd
Xd
Provide/ review diary card
X
X
Corticosteroid administration 
(dexamethasone) 
(refer to Section 7.2) for doses 3.6 mg and 
above
X
X
X
X
X
X
IV administration of CC-90009e
X
X
X
X
X
X
Monitoring as inpatient 
X
X
X
X
X
X
X
X
Safety Assessments (Section 6)
Adverse Event Evaluation (Section 6.2.2)
X
X
X
X
X
X
X
X
X
X
X
X
X
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Table 31:
Table of Events for Part A (D1-3/D8-10 Schedule) of Cycle 1
Eventsa
Screening
Treatment Period
Cycle 1
WK1
WK2
WK3
WK4
WK5
WK6b
D-28 to -1
D1
D2
D3
D4
D8
D9
D10
D11
D15
D22
D28c
D29
D36
Height 
X
Weight (Section 6.2.3)
X
X
X
X
X
Vital Signs (Section 6.2.3)
X
Xf
Xf
Xf
X
Xf
Xf
Xf
X
X
X
X
X
Physical Examination (Section 6.2.4)
X
X
X
ECOG PS (Appendix D)
X
X
X
12-lead ECG (in triplicate, Section 6.2.5)
X (≥72 hrs 
prior to D1)
Xf
Xf
LVEF (ECHO/MUGA scan; Section 6.2.6)
X
Pregnancy testing per PPP (FCBP only; 
Section 6.2.7)
Xg
X
X
X
X
Hematology laboratory tests (Section 6.2.8)
X 
(D-14 to -1)
X
X
X
X
X
X
X
X
X
X
X
X
G6PD (Section 6.2.8)
X
Serum chemistry laboratory tests 
(Section 6.2.8)h
X 
(D-3 to -1)
Xi
Xi
Xi
X
X
X
X
X
X
X
X
X
Additional serum Ca, Mg and PTH  tests 
(Section 6.2.8)h
Xj
Xj
Xj
Xj
Xj
Xj
Serum PTH, P1NP, β-CTx tests 
(Section 6.2.8)
X
X
X
X
Serum 25-hydroxyvitamin D level 
(Section 6.2.8)
X
X
Urine Ca/ creatinine ratio (random) 
(Section 6.2.8)
X
X
X
X
Amylase, lipase, T-cell subsets (CD4+ and 
CD8+), TSH (Section 6.2.8)
X
PT, INR, PTT (Section 6.2.8)k
X
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Table 31:
Table of Events for Part A (D1-3/D8-10 Schedule) of Cycle 1
Eventsa
Screening
Treatment Period
Cycle 1
WK1
WK2
WK3
WK4
WK5
WK6b
D-28 to -1
D1
D2
D3
D4
D8
D9
D10
D11
D15
D22
D28c
D29
D36
Urinalysis (Section 6.2.8)
X 
(D-14 to -1)
PK & PD Assessments
Blood, PK (Section 6.5)
Xl
X
Xl
X
Xl
X
X
X
Urine, PK (Section 6.5) selected subjectsr
X
Pharmacogenomics sample (eg, buccal cells 
or nail clippings), (Section 6.6.1)
X
Blood (whole), biomarker flow cytometry 
(Section 6.6.2)
X 
(D-14 to -1)
X
X
Xl
X
X
X
X
Blood (PBMCs), PD protein and RNA 
(Section 6.6.2)
X 
(D-14 to -1)
X
X
X
X
X
Blood (PBMCs), PD ex vivo sensitivity 
assays, phenotyping & sequencing 
(Section 6.6.2)
X
Blood (plasma), PD cytokines (Section 6.6.2)
X 
(D-14 to -1)
X
X
X
X
X
X
X
Bone marrow aspirate and biopsy, PD 
biomarkers & MRD (Section 6.6.3)m
X 
(D-14 to -1)
Xn
Xo
(±3d)
Efficacy 
Bone marrow aspiration and biopsy, 
complete blood counts and examination of 
peripheral blood smears (Section 6.4)o
X 
(D-14 to -1)
Xo
(±3d)
Xp,q
(only 
on 
D42 ± 
3d)
Abbreviations:  β-CTx = beta C-terminal telopeptide; C = cycle; Ca = calcium; CD = cluster of differentiation; D = day; ECHO = echocardiogram; ECG = electrocardiogram; ECOG 
PS = Eastern Cooperative Oncology Group performance status; FCBP = females of child bearing potential; G6PD = glucose-6-phosphate dehydrogenase; hrs = hours; INR = 
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international normalized ratio; IRT = integrated response technology; IV = intravenous; LVEF = left ventricular ejection fraction; Mg = magnesium; MRD = Minimal Residual 
Disease; MUGA = multi-gated acquisition scan; P1NP = procollagen type 1 N-terminal propeptide; PBMC = peripheral blood mononuclear cells; PD = pharmacodynamic; PK = 
pharmacokinetic; PPP = pregnancy prevention plan; PT = prothrombin time; PTH = parathyroid hormone; PTT = partial thromboplastin time; RNA = ribonucleic acid; TSH = 
thyroid-stimulating hormone; WK = week. 
a All study visits/procedures will have a ± 2 day window and all laboratory blood samples should be drawn predose (≤ 5 hrs), unless otherwise specified in this table or Section 6.
b Subjects with hypoplastic bone marrow without evidence of persistent AML at the Day 28 assessment who have Grade ≥ 3 neutropenia will be followed for an additional 2 weeks 
for safety monitoring in Cycle 1 (total duration of 42 days; refer to Figure 1). Not all visits are shown as separate columns under Week 6, ie, Day 42 bone marrow assessment. 
c Eligible subjects continue on to Cycle 2 (refer to Table 5).  Based on the Day 28 bone marrow evaluation, subjects with a hypoplastic bone marrow without evidence of persistent 
leukemia who have Grade ≥ 3 neutropenia will be followed for an additional 2 weeks for safety monitoring in Cycle 1. 
d Supplementation may be prolonged if hypocalcemia occurs (refer to Section 7.2.13.2). Subjects are to start supplements at least 3 days prior to Day 1 of Cycle 2 as per Section 7.2.
e Subjects will be closely monitored during administration of CC-90009 and for at least one hour after. Subjects should be adequately hydrated to prevent potential tumor lysis 
syndrome (TLS) (eg, 2 to 3 liters of oral or IV fluids per day) starting the day prior to CC-90009 administration and continuing through each day of CC-90009 administration. Refer 
to Section 7.2.12 for information on dose interruptions. The SRC may decide to evaluate alternate dosing schedules (eg, increasing from 5 to up to 10 consecutive days of CC-
90009 administration) based on their review of available clinical and laboratory safety data, PK profiles, and PD findings. 
f Multiple measurements performed on this day. 
g Two pregnancy tests (sensitivity of at least 25 mIU/mL) must be performed prior to first dose of CC-90009:  within 10 to 14 days prior and within 24 hours prior. Both tests must 
be negative for CC-90009 dosing to begin. 
h A free (ionized) serum calcium test should be obtained at Screening to establish baseline values in addition to the corrected serum calcium test (corrected for albumin) used to 
fulfill the inclusion criteria. In the event of Grade ≥ 2 hypocalcemia or symptoms of hypocalcemia (eg, carpopedal spasm, tetany, seizures, etc), subjects must be hospitalized. 
Also, if Grade ≥ 2 hypocalcemia and abnormal levels of serum albumin occurs, a serum ionized calcium test must be performed. Refer to Section 7.2.13.2 for hypocalcemia 
management guidelines.
i
Specific tests for TLS monitoring required predose and 12 hours (± 1 hour) postdose on Days 1, 2, and 3. Refer to Section 6.2.8. 
j
Additional serum calcium/magnesium tests required 6 and 12 hours (± 1 hour) postdose on days of CC-90009 administration. Additional PTH tests required at 6 hours (± 1 hours) 
post-dose on days of CC-90009 administration.
k Subsequent coagulation tests only performed for subjects on anticoagulant therapy and as clinically indicated. 
l
Multiple blood samples will be collected for this assay on the specified day. Refer to Sections 6.5 and 6.6.
m Bone marrow samples for biomarker assessment are mandatory. If bone marrow samples are scheduled to be collected on the same day for efficacy, the biomarker samples should 
be collected at the same time. If sufficient bone marrow aspirate specimen is not available, peripheral blood may be submitted in place of the BMA specimen for biomarker studies 
(eg, MRD); see laboratory manual for details.
n Obtained between 4 to 8 hours postdose. The samples may be obtained on Day 9 if necessary due to scheduling difficulties. 
o Additional aspirates and biopsies will be collected as clinically indicated (eg, Cycle 1 Day 15 based on Investigator’s medical assessment). 
p Molecular and cytogenetic studies may be omitted at: Screening, if they were completed within the previous 90 days and the results are available for recording on the electronic 
case report forms and Day 42 (or at hematologic recovery) if a complete response is documented at Day 28.  
q Additional bone marrow assessment performed at the time of hematologic recovery or Day 42 (± 3 days).  Eligible subjects continue on to Cycle 2 (refer to Table 5).
r Urine PK to be performed on approximately 10 selected subjects from Part A and/or Part B.  This is a 24-hour collection that starts C1D1 and ends C1D2.
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Table 32:
Table of Events for Part A (D1-3/D8-10 Schedule) of Cycle ≥ 2
Eventsa
Treatment Period
Follow-up Period
Cycles ≥2
EOTb
Safetyc
WK1
WK2
WK3
WK4
D1
D2
D3
D4
D8
D9
D10
D11
D15
D22
D28
≤28 
days
28 days
(± 3 d)
Long 
Term
Review concomitant medications & procedures 
(Section 6.2.1)
X
X
X
X
X
X
X
X
X
X
X
X
CC-90009 Administration (Section 7)
Calcium, calcitriol and Vitamin D supplements and 
recording on diary card (Section 7.2)
X
X
X
X
(D4-7)
X
X
Xd
X (C2 
& C3)d
Provide/ review of diary card
X
X
Corticosteroid administration (dexamethasone) 
(refer to Section 7.2) for doses 3.6 mg and above
X
X
X
X
X
X
IV administration of CC-90009e
X
X
X
X
X
X
Safety Assessments (Section 6)
Adverse Event Evaluation (Section 6.2.2)
X
X
X
X
X
X
X
X
X
X
X
X
Weight (Section 6.2.3)
X
X
Vital Signs (Section 6.2.3)
Xf
Xf
Xf
X
Xf
Xf
Xf
X
X
X
X
Physical Examination (Section 6.2.4)
X
X
ECOG PS (Appendix D)
X
X
12-lead ECG (Section 6.2.5)g
X
X
LVEF (ECHO/MUGA; Section 6.2.6)
X (only 
C2 ± 7d)
X 
(± 7d)h
Pregnancy test (FCBP only; Section 6.2.7) 
X
Xi
Xi
Xi
Pregnancy risk counseling and contraceptive 
compliance confirmation 
X
As specified in Section 6.1.1 and the PPP in Appendix L
Hematology laboratory (Section 6.2.8)
X
X
X
X
X
X
X
X
X
X
X
Serum chemistry laboratory tests (Section 6.2.8)j
X
X
X
X
X
X
Serum Ca & Mg tests  (Section 6.2.8)j
Xj
Xj
Xj
Xj
Xj
Xj
Serum PTH, P1NP, β-CTx tests (Section 6.2.8)
X
X
X
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Table 32:
Table of Events for Part A (D1-3/D8-10 Schedule) of Cycle ≥ 2
Eventsa
Treatment Period
Follow-up Period
Cycles ≥2
EOTb
Safetyc
WK1
WK2
WK3
WK4
D1
D2
D3
D4
D8
D9
D10
D11
D15
D22
D28
≤28 
days
28 days
(± 3 d)
Long 
Term
Serum 25-hydroxyvitamin D level (Section 6.2.8)
X
Urine Ca/ creatinine ratio test (random) (Section 6.2.8)
X
X
X
Amylase, lipase, T-cell subsets (CD4+ and CD8+), 
TSH (Section 6.2.8)
X
X
PT, INR, PTT (for subjects on anticoagulant therapy) 
(Section 6.2.8)
X
X
Urinalysis (Section 6.2.8)
X
X
PK/PD Assessments
Blood, PK (Section 6.5) for Cycle 2 only
X
X
X
X
X
X
X
X
Bone marrow aspirate and biopsy, PD biomarkers & 
MRD (Section 6.6.3)k,l
X (C2 
and C4; 
± 3d)
Xm
Refer to 
Section 
6.3.2
Efficacy
Complete blood counts and examination of peripheral 
blood smears (Section 6.4)l
X (C2 
and C4; 
± 3d)
Xm
Refer to 
Section 
6.3.2
Bone marrow aspirate and biopsy (Section 6.4)m
X (C2 
and C4; 
± 3d)
Xm
Refer to 
Section 
6.3.2
Follow-up 
CC-90009-related AE/SAE follow-up
Refer to Section 6.3.1
Anticancer therapies 
Refer to Section 6.3.2
Survival 
Refer to Section 6.3.3
Abbreviations:  Adverse event = AE; β-CTx = beta C-terminal telopeptide; C = cycle; Ca = calcium; CD = cluster of differentiation; D = day; ECHO = echocardiogram; ECG = 
electrocardiogram; ECOG PS = Eastern Cooperative Oncology Group performance status; EOT = End of Treatment; FCBP = females of child bearing potential; INR = international 
normalized ratio; IV = intravenous; LVEF = left ventricular ejection fraction; Mg = magnesium; MUGA = multi-gated acquisition scan; P1NP = procollagen type 1 N-terminal 
propeptide; PD = pharmacodynamic; PPP = pregnancy prevention plan; PT = prothrombin time; PTH = parathyroid hormone; PTT = partial thromboplastin time; q = every; SAE = 
serious adverse event; TSH = thyroid-stimulating hormone; WK = week. 
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a All study visits/procedures will have a ± 2 day window and all laboratory blood samples should be drawn predose (≤ 5 hrs), unless otherwise specified in this table or Section 6. 
Cycles should start ≤ 7 days after the last day of the previous cycle. 
b EOT Visit performed within 28 days after last dose of CC-90009 for subjects that discontinue prior to completing dosing in Cycle 4. For subjects that complete dosing in Cycle 4, 
this visit should be completed on Day 28 (± 2 days) of Cycle 4.  For subjects who complete dosing after Cycle 4, EOT Visit should be completed within 28 days after the last day 
of the previous cycle. 
c Safety Follow-up Visit is performed 28 days (± 3 days) after the last dose of CC-90009 for all subjects. May be performed by telephone contact if pregnancy testing is not required 
(refer to footnote “i”). 
d Supplements to be administered for at least 3 days after the last dose in each cycle. Supplementation may be prolonged if hypocalcemia occurs (refer to Section 7.2.13.2). Subjects 
to start supplements at least 3 days prior to Day 1 of Cycles 3 and 4 as per Section 7.2.
e Subjects will be closely monitored during the administration of CC-90009 and for at least 1 hour after. Subjects should be adequately hydrated to prevent potential tumor lysis 
syndrome (TLS) (eg, 2 to 3 liters of oral or IV fluids per day) starting the day prior to CC-90009 administration and continuing through each day of CC-90009 administration. Refer 
to Section 7.2.12 for information on dose interruptions. The SRC may decide to evaluate alternate dosing schedules (eg, increasing from 5 to up to 10 consecutive days of CC-
90009 administration) based on their review of available clinical and laboratory safety data, PK profiles, and PD findings. Subjects should be administered CC-90009 in a Limited 
Stay Unit (LSU) or as in patient. Subjects experiencing Grade ≥ 2 hypocalcemia during any cycle should be administered CC-90009 in the inpatient setting for subsequent cycles 
(an exception can be made for subjects with grade 2 hypocalcemia lasting less than 24 hours that recovers without IV calcium [eg, calcium gluconate or calcium chloride] after 
discussion with the Celgene medical monitor).
f Multiple measurements performed on this day. 
g Triplicate ECGs will be performed on Day 1 of each cycle (refer to Section 6.2.5) and a single ECG obtained at the EOT visit. 
h The EOT Visit LVEF is not required if the prior LVEF was performed within 56 days. 
i
Per the PPP, a pregnancy test is required 28 days after the last dose of for all FCBP. For FCBP with irregular menstrual periods, a pregnancy test is required every 14 days (ie, 
Day 15 of Cycles ≥ 2 and at 14 and 28 days after the last dose of CC-90009).
j
In the event of Grade ≥ 2 hypocalcemia or symptoms of hypocalcemia (eg, carpopedal spasm, tetany, seizures, etc), subjects must be hospitalized. Also, if Grade ≥ 2 hypocalcemia 
and abnormal levels of serum albumin occurs, a serum ionized calcium test must be performed. Refer to Section 7.2.13.2 for hypocalcemia management guidelines. Refer to 
Section 6.2.8 for required days and timing of tests. Subjects who experienced Grade ≥ 2 hypocalcemia during Cycle 1, require testing all dosing days at 6 and 12 hours postdose. 
k Bone marrow samples for biomarker PD assessment are mandatory. When applicable (refer to time points in the table above), bone marrow samples for biomarker PD assessment 
will be obtained at the same time as a scheduled efficacy assessment. If sufficient bone marrow aspirate specimen is not available, peripheral blood may be submitted in place of 
the BMA specimen for biomarker studies (eg, MRD); see laboratory manual for details.
l
If end of Cycle 2 (Day 28 ± 3 days) samples are obtained on Day 1 of Cycle 3, they must be obtained prior to CC-90009 administration. Additionally, bone marrow aspirates and 
biopsies may be obtained in both Part A and Part B, after a CR is confirmed, if relapse is suspected, or following treatment discontinuation to elucidate effects of long-term 
treatment or resistance mechanisms. Additional aspirates and biopsies will be collected as clinically indicated based on the Investigator’s medical assessment.
m For subjects that complete dosing in Cycle 4, performed/obtained once on Day 28 (± 3 days). For subjects that continue (after consultation with Medical Monitor) beyond Cycle 
4, efficacy and bone marrow PD assessments may be obtained to confirm a CR, if relapse is suspected, or following treatment discontinuation to elucidate effects of long-term 
treatment or resistance mechanisms. Additional aspirates and biopsies will be collected as clinically indicated based on the Investigator’s medical assessment. Refer to Section 
6.3.2 and Section 6.4.
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Appendix L:
CC-90009 Pregnancy Prevention Plan
Specific details regarding the CC-90009 Pregnancy Prevention Plan (PPP) will be provided via a 
separate, stand-alone document.
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Appendix M:
Part A Table of Events for D1-7 Dosing Schedule
Table 33:
Table of Events for Part A (D1-7 Schedule) of Cycle 1
Screening
Treatment Period
Cycle 1
WK1
WK2
WK3
WK4
WK5b
WK6b
Eventsa
D-28 to -1
D1
D2
D3
D4
D5
D6
D7
D8
D15
D22
D28c
D29
D36
Study Entry (Section 6.1)
Informed consent 
X
Inclusion/ exclusion criteria
X
Medical/ oncologic history 
X
Demographics 
X
IRT registration
X
X
Pregnancy risk counseling and 
contraceptive compliance 
confirmation
X
As specified in Section 6.1.1 and the PPP in Appendix L
Prior/ concomitant medications & 
procedures (Section 6.2.1)
X
X
X
X
X
X
X
X
X
X
X
X
X
CC-90009 Administration (Section 7)
Calcium, calcitriol, and vitamin D 
supplements and recording on diary 
card (refer to Section 7.2)
X (D-3 to 
D-1)
X
X
X
X
X
X
X
Xd
Xd
Xd
Provide/ review diary card
X
X
Corticosteroid administration 
(dexamethasone) 
(refer to Section 7.2) for doses 3.6 
mg and above
X
X
X
X
X
X
X
IV administration of CC-90009e
X
X
X
X
X
X
X
Monitoring as inpatient 
X
X
X
X
X
X
X
Safety Assessments (Section 6)
Adverse Event Evaluation 
(Section 6.2.2)
X
X
X
X
X
X
X
X
X
X
X
X
X
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Table 33:
Table of Events for Part A (D1-7 Schedule) of Cycle 1
Screening
Treatment Period
Cycle 1
WK1
WK2
WK3
WK4
WK5b
WK6b
Eventsa
D-28 to -1
D1
D2
D3
D4
D5
D6
D7
D8
D15
D22
D28c
D29
D36
Height
X
Weight (Section 6.2.3)
X
X
X
X
X
Vital Signs (Section 6.2.3)
X
Xf
Xf
Xf
Xf
Xf
Xf
Xf
X
X
X
X
X
Physical Examination (Section 6.2.4)
X
X
X
ECOG PS (Appendix D)
X
X
X
12-lead ECG (in triplicate, 
Section 6.2.5)
X (≥72 hrs 
prior to 
D1)
Xf
Xf
X
LVEF (ECHO/MUGA scan; 
Section 6.2.6)
X
Pregnancy testing per PPP (FCBP 
only; Section 6.2.7)
Xg
X
X
X
X
Hematology laboratory tests 
(Section 6.2.8)
X (D-14 
to -1)
X
X
X
X
X
X
X
X
X
X
X
X
G6PD (Section 6.2.8)
X
Serum chemistry laboratory tests 
(Section 6.2.8)h
X
(D-3 to -1)
Xi
Xi
Xi
X
X
X
X
X
X
X
X
X
Additional serum Ca, Mg and PTH 
tests (Section 6.2.8)h
Xj
Xj
Xj
Xj
Xj
Xj
Xj
Serum PTH, P1NP, β-CTx tests 
(Section 6.2.8)
X
X
X
X
Serum 25-hydroxyvitamin D level 
(Section 6.2.8)
X
X
Urine Ca/ creatinine ratio (random) 
(Section 6.2.8)
X
X
X
X
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Table 33:
Table of Events for Part A (D1-7 Schedule) of Cycle 1
Screening
Treatment Period
Cycle 1
WK1
WK2
WK3
WK4
WK5b
WK6b
Eventsa
D-28 to -1
D1
D2
D3
D4
D5
D6
D7
D8
D15
D22
D28c
D29
D36
Amylase, lipase, T-cell subsets 
(CD4+ and CD8+), TSH 
(Section 6.2.8)
X
PT, INR, PTT (Section 6.2.8)k
X
Urinalysis (Section 6.2.8)
X
(D-14 
to -1)
X
PK & PD Assessments
Blood, PK (Section 6.5)
Xl
X
Xl
X
Xl
Urine, PK (Section 6.5) selected 
subjectsr
X
Pharmacogenomics sample (eg, 
buccal cells or nail clippings), 
(Section 6.6.1)
X
Blood (whole), biomarker flow 
cytometry (Section 6.6.2)
X
(D-14 
to -1)
Xl
Xl
Xl
X
X
Blood (PBMCs), PD protein and 
RNA (Section 6.6.2)
X
(D-14 
to -1)
Xl
X
X
X
Blood (PBMCs), PD ex vivo 
sensitivity assays, phenotyping & 
sequencing (Section 6.6.2)
X
Blood (plasma), PD cytokines 
(Section 6.6.2)
X
(D-14 
to -1)
X
X
X
X
X
Bone marrow aspirate and biopsy, 
PD biomarkers & MRD (Section 
6.6.3)m
X
(D-14 
to -1)
Xn
X 
(± 3d)
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Table 33:
Table of Events for Part A (D1-7 Schedule) of Cycle 1
Screening
Treatment Period
Cycle 1
WK1
WK2
WK3
WK4
WK5b
WK6b
Eventsa
D-28 to -1
D1
D2
D3
D4
D5
D6
D7
D8
D15
D22
D28c
D29
D36
Efficacy 
Bone marrow aspiration and biopsy, 
complete blood counts and 
examination of peripheral blood 
smears (Section 6.4)o
X 
(D-14 
to -1)p
X 
(± 3d)
X (only 
on D42 
± 3d)q
Abbreviations:  β-CTx = beta C-terminal telopeptide; C = cycle; Ca = calcium; CD = cluster of differentiation; D = day; ECHO = echocardiogram; ECG = electrocardiogram; 
ECOG PS = Eastern Cooperative Oncology Group performance status; FCBP = females of child bearing potential; G6PD = glucose-6-phosphate dehydrogenase; hrs = hours; INR 
= international normalized ratio; IRT = integrated response technology; IV = intravenous; LVEF = left ventricular ejection fraction; Mg = magnesium; MRD = Minimal Residual 
Disease; MUGA = multi-gated acquisition scan; P1NP = procollagen type 1 N-terminal propeptide; PBMC = peripheral blood mononuclear cells; PD = pharmacodynamic; PK = 
pharmacokinetic; PPP = pregnancy prevention plan; PT = prothrombin time; PTH = parathyroid hormone; PTT = partial thromboplastin time; RNA = ribonucleic acid; TSH = 
thyroid-stimulating hormone; WK = week. 
a All study visits/procedures will have a ± 2 day window and all laboratory blood samples should be drawn predose (≤ 5 hrs), unless otherwise specified in this table or Section 
6.
b Subjects with hypoplastic bone marrow without evidence of persistent AML at the Day 28 assessment who have Grade ≥ 3 neutropenia will be followed for an additional 
2 weeks for safety monitoring in Cycle 1 (total duration of 42 days; refer to Figure 1). Not all visits are shown as separate columns under Week 6, ie, Day 42 bone marrow 
assessment. 
c Eligible subjects continue on to Cycle 2 (refer to Table 5).  Based on the Day 28 bone marrow evaluation, subjects with a hypoplastic bone marrow without evidence of 
persistent leukemia who have Grade ≥ 3 neutropenia will be followed for an additional 2 weeks for safety monitoring in Cycle 1. 
d Supplementation may be prolonged if hypocalcemia occurs (refer to Section 7.2.13.2). Subjects are to start supplements at least 3 days prior to Day 1 of Cycle 2 as per 
Section 7.2.
e Subjects will be closely monitored during administration of CC-90009 and for at least one hour after. Subjects should be adequately hydrated to prevent potential tumor lysis 
syndrome (TLS) (eg, 2 to 3 liters of oral or IV fluids per day) starting the day prior to CC-90009 administration and continuing through each day of CC-90009 
administration. Refer to Section 7.2.12 for information on dose interruptions. The SRC may decide to evaluate alternate dosing schedules (eg, increasing from 5 to up to 
10 consecutive days of CC-90009 administration) based on their review of available clinical and laboratory safety data, PK profiles, and PD findings. 
f Multiple measurements performed on this day. 
g Two pregnancy tests (sensitivity of at least 25 mIU/mL) must be performed prior to first dose of CC-90009:  within 10 to 14 days prior and within 24 hours prior. Both tests 
must be negative for CC-90009 dosing to begin. 
h A free (ionized) serum calcium test should be obtained at Screening to establish baseline values in addition to the corrected serum calcium test (corrected for albumin) used to 
fulfill the inclusion criteria. In the event of Grade ≥ 2 hypocalcemia or symptoms of hypocalcemia (eg, carpopedal spasm, tetany, seizures, etc), subjects must be hospitalized. 
Also, if Grade ≥ 2 hypocalcemia and abnormal levels of serum albumin occurs, a serum ionized calcium test must be performed. Refer to Section 7.2.13.2 for hypocalcemia 
management guidelines.
i
Specific tests for TLS monitoring required predose and 12 hours (± 1 hour) postdose on Days 1, 2, and 3. Refer to Section 6.2.8. 
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j
Additional serum calcium/magnesium tests required 6 and 12 hours (± 1 hour) postdose on days of CC-90009 administration. Additional PTH tests required at 6 hours (± 1 
hours) post-dose on days of CC-90009 administration.
k Subsequent coagulation tests only performed for subjects on anticoagulant therapy and as clinically indicated. 
l
Multiple blood samples will be collected for this assay on the specified day. Refer to Sections 6.5 and 6.6.
m Bone marrow samples for biomarker assessment are mandatory. If bone marrow samples are scheduled to be collected on the same day for efficacy, the biomarker samples 
should be collected at the same time. If sufficient bone marrow aspirate specimen is not available, peripheral blood may be submitted in place of the BMA specimen for 
biomarker studies (eg, MRD); see laboratory manual for details.
n Obtained between 4 to 8 hours postdose. The samples may be obtained on Day 6 or Day 8 if necessary due to scheduling difficulties. If the dosing interval (schedule) is 
extended, then samples will be obtained on the last day ±1 day of dosing (eg, if extended to 10 day, obtain on Day 9-11).
o Additional aspirates and biopsies will be collected as clinically indicated (eg, Cycle 1 Day 15 based on Investigator’s medical assessment). 
p Molecular and cytogenetic studies may be omitted at:  Screening, if they were completed within the previous 90 days and the results are available for recording on the electronic 
case report forms and Day 42 (or at hematologic recovery), if a complete response is documented at Day 28.  
q Additional bone marrow assessment performed at the time of hematologic recovery or Day 42 (± 3 days).  Eligible subjects continue on to Cycle 2 (refer to Table 5).
r Urine PK to be performed on approximately 10 selected subjects from Part A and/or Part B. This is a 24-hour collection that starts on C1D1 and ends on C1D2. 
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Table 34:
Table of Events for Part A (D1-7 Schedule) of Cycles ≥ 2
Treatment Period
Follow-up Period
Cycles ≥ 2
WK1
WK2
WK3
WK4
EOTb
Safetyc
Eventsa
D1
D2
D3
D4
D5
D6
D7
D8
D15
D22
D28
≤ 28 days
28 days 
(± 3 days)
Long 
Term
Review concomitant medications & 
procedures (Section 6.2.1)
X
X
X
X
X
X
X
X
X
X
X
X
CC-90009 Administration (Section 7)
Calcium, calcitriol and Vitamin D 
supplements and recording on diary 
card (Section 7.2)
X
X
X
X
X
X
X
Xd
X (C2 
and 
C3)d
Provide/ review of diary card
X
X
Corticosteroid administration 
(dexamethasone) (refer to Section 7.2) 
for doses 3.6 mg and above
X
X
X
X
X
X
X
IV administration of CC-90009e
X
X
X
X
X
X
X
Safety Assessments (Section 6)
Adverse Event Evaluation (Section 
6.2.2)
X
X
X
X
X
X
X
X
X
X
X
X
Weight (Section 6.2.3)
X
X
Vital Signs (Section 6.2.3)
Xf
Xf
Xf
Xf
Xf
Xf
Xf
X
X
X
X
Physical Examination (Section 6.2.4)
X
X
ECOG PS (Appendix D)
X
X
12-lead ECG (Section 6.2.5)g
X
X
LVEF (ECHO/MUGA; Section 6.2.6)
X (only 
C2 ± 
7d)
X (± 7d)h
Pregnancy test (FCBP only; 
Section 6.2.7) 
X
Xi
Xi
Xi
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Table 34:
Table of Events for Part A (D1-7 Schedule) of Cycles ≥ 2
Treatment Period
Follow-up Period
Cycles ≥ 2
WK1
WK2
WK3
WK4
EOTb
Safetyc
Eventsa
D1
D2
D3
D4
D5
D6
D7
D8
D15
D22
D28
≤ 28 days
28 days 
(± 3 days)
Long 
Term
Pregnancy risk counseling and 
contraceptive compliance confirmation
X
As specified in Section 6.1.1 and the PPP in Appendix L
Hematology laboratory (Section 6.2.8)
X
X
X
X
X
X
X
X
X
X
X
Serum chemistry laboratory tests 
(Section 6.2.8)j
X
X
X
X
X
X
Serum Ca & Mg tests (Section 6.2.8)j
Xj
Xj
Xj
Xj
Xj
Xj
Xj
Serum PTH, P1NP, β-CTx tests 
(Section 6.2.8)
X
X
X
Serum 25-hydroxyvitamin D level 
(Section 6.2.8)
X
Urine Ca/ creatinine ratio test (random) 
(Section 6.2.8)
X
X
X
Amylase, lipase, T-cell subsets (CD4+ 
and CD8+), TSH (Section 6.2.8)
X
X
PT, INR, PTT (for subjects on 
anticoagulant therapy) (Section 6.2.8)
X
X
Urinalysis (Section 6.2.8)
X
X
PK & PD Assessments
Blood, PK (Section 6.5)o
X
X
X
X
Xo
Blood (whole), biomarker flow 
cytometry, (Section 6.6.2) first cycle of 
intra-subject dose escalation onlyk
Xk
Xk
Xk
Xk
Xk
Blood (PBMCs), PD protein and RNA 
(Section 6.6.2) first cycle of intra-
subject dose escalation onlyk
Xk
Xk
Xk
Xk
1.0
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Final: 31 Mar 2022
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Table 34:
Table of Events for Part A (D1-7 Schedule) of Cycles ≥ 2
Treatment Period
Follow-up Period
Cycles ≥ 2
WK1
WK2
WK3
WK4
EOTb
Safetyc
Eventsa
D1
D2
D3
D4
D5
D6
D7
D8
D15
D22
D28
≤ 28 days
28 days 
(± 3 days)
Long 
Term
Blood (plasma), PD cytokines 
(Section 6.6.2) first cycle of intra-
subject dose escalation onlyk
X
X
X
X
X
Bone marrow aspirate and biopsy, PD 
biomarkers & MRD (Section 6.6.3)l, m
X (C2 
and 
C4; ± 
3d)
Xn
Refer to 
Section 
6.3.2
Efficacy 
Complete blood counts and 
examination of peripheral blood smears 
(Section 6.4)m
X (C2 
and 
C4; ± 
3d)
Xn
Refer to 
Section 
6.3.2
Bone marrow aspirate and biopsy 
(Section 6.4)m
X (C2 
and 
C4; ± 
3d)
Xn
Refer to 
Section 
6.3.2
Follow-up 
CC-90009-related AE/SAE follow-up
Refer to Section 6.3.1
Anticancer therapies 
Refer to Section 6.3.2
Survival 
Refer to Section 6.3.3
Abbreviations:  Adverse event = AE; β-CTx = beta C-terminal telopeptide; C = cycle; Ca = calcium; CD = cluster of differentiation; D = day; ECHO = echocardiogram; ECG = 
electrocardiogram; ECOG PS = Eastern Cooperative Oncology Group performance status; EOT = End of Treatment; FCBP = females of child bearing potential; INR = international 
normalized ratio; IV = intravenous; LVEF = left ventricular ejection fraction; Mg = magnesium; MUGA = multi-gated acquisition scan; P1NP = procollagen type 1 N-terminal 
propeptide; PD = pharmacodynamics; PPP = pregnancy prevention plan; PT = prothrombin time; PTH = parathyroid hormone; PTT = partial thromboplastin time; q = every; SAE 
= serious adverse event; TSH = thyroid-stimulating hormone; WK = week. 
a All study visits/procedures will have a ± 2 day window and all laboratory blood samples should be drawn predose (≤ 5 hrs), unless otherwise specified in this table or Section
6. Cycles should start ≤ 7 days after the last day of the previous cycle. 
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b EOT Visit performed within 28 days after last dose of CC-90009 for subjects that discontinue prior to completing dosing in Cycle 4. For subjects that complete dosing in Cycle 
4, this visit should be completed on Day 28 (± 2 days) of Cycle 4.  For subjects who complete dosing after Cycle 4, EOT Visit should be completed within 28 days after the 
last day of the previous cycle. 
c Safety Follow-up Visit is performed 28 days (± 3 days) after the last dose of CC-90009 for all subjects. May be performed by telephone contact if pregnancy testing is not 
required (refer to footnote “i”). 
d Supplements to be administered for at least 3 days after the last dose in each cycle. Supplementation may be prolonged if hypocalcemia occurs (refer to Section 7.2.13.2). 
Subjects to start supplements at least 3 days prior to Day 1 of Cycles 3 and 4 as per Section 7.2.
e Subjects will be closely monitored during the administration of CC-90009 and for at least 1 hour after. Subjects should be adequately hydrated to prevent potential tumor lysis 
syndrome (TLS) (eg, 2 to 3 liters of oral or IV fluids per day) starting the day prior to CC-90009 administration and continuing through each day of CC-90009 
administration. Refer to Section 7.2.12 for information on dose interruptions. The SRC may decide to evaluate alternate dosing schedules (eg, increasing from 5 to up to 
10 consecutive days of CC-90009 administration) based on their review of available clinical and laboratory safety data, PK profiles, and PD findings. Subjects should be 
administered Cycle ≥ 2 of CC-90009 in a Limited Stay Unit (LSU) or as in patient. Subjects experiencing Grade ≥ 2 hypocalcemia during any cycle should be administered 
CC-90009 in the inpatient setting for subsequent cycles (an exception can be made for subjects with grade 2 hypocalcemia lasting less than 24 hours that recovers without IV 
calcium [eg, calcium gluconate or calcium chloride] after discussion with the Celgene medical monitor).
f Multiple measurements performed on this day. 
g Triplicate ECGs will be performed on Day 1 of each cycle (refer to Section 6.2.5) and a single ECG obtained at the EOT visit. 
h The EOT Visit LVEF is not required if the prior LVEF was performed within 56 days. 
I Per the PPP, a pregnancy test is required 28 days after the last dose of for all FCBP. For FCBP with irregular menstrual periods, a pregnancy test is required every 14 days (ie, 
Day 15 of Cycles ≥ 2 and at 14 and 28 days after the last dose of CC-90009).
j
In the event of Grade ≥ 2 hypocalcemia or symptoms of hypocalcemia (eg, carpopedal spasm, tetany, seizures, etc), subjects must be hospitalized. Also, if Grade ≥ 2 
hypocalcemia and abnormal levels of serum albumin occurs, a serum ionized calcium test must be performed. Refer to Section 7.2.13.2 for hypocalcemia management 
guidelines. Refer to Section 6.2.8 for required days and timing of tests. Subjects who experienced Grade ≥ 2 hypocalcemia during Cycle 1, require testing Days 1-7 at 6 and 
12 hours postdose. All other subjects require testing prior to dosing. If intra-subject dose escalation occurs, subjects should be treated as in Cycle 1.
k If intra-subject dose escalation occurs, blood samples for PD assays will be collected during the first cycle only at the increased dose; see laboratory manual for details. Multiple 
blood samples will be collected for this assay on the specified Days 1, 2, 3. Refer to Section 6.6. 
l
Bone marrow samples for biomarker PD assessment are mandatory. When applicable (refer to time points in the table above), bone marrow samples for biomarker PD 
assessment will be obtained at the same time as a scheduled efficacy assessment. If sufficient bone marrow aspirate specimen is not available, peripheral blood may be 
submitted in place of the BMA specimen for biomarker studies (eg, MRD); see laboratory manual for details.
m If end of Cycle 2 (Day 28 ± 3 days) samples are obtained on Day 1 of Cycle 3, they must be obtained prior to CC-90009 administration. Additionally, bone marrow aspirates 
and biopsies may be obtained in both Part A and Part B, after a CR is confirmed, if relapse is suspected, or following treatment discontinuation to elucidate effects of long-
term treatment or resistance mechanisms. Additional aspirates and biopsies will be collected as clinically indicated based on the Investigator’s medical assessment.
n For subjects that complete dosing in Cycle 4, performed/obtained once on Day 28 (± 3 days). For subjects that continue (after consultation with Medical Monitor) beyond 
Cycle 4, efficacy and bone marrow PD assessments may be obtained to confirm a CR, if relapse is suspected, or following treatment discontinuation to elucidate effects of 
long-term treatment or resistance mechanisms. Additional aspirates and biopsies will be collected as clinically indicated based on the Investigator’s medical assessment. Refer 
to Section 6.3.2 and Section 6.4.
o
Blood samples for PK are to be collected in Cycle 2 only; on Day 7 there is a pre-dose and 24 hour postdose sample Section 6.5.1.
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Appendix N:
Part B Table of Events for D1-7 Dosing Schedule
Table 35:
Table of Events for Part B (D1-7 Schedule) of Cycle 1
Eventsa
Screening
Treatment Period
Cycle 1
WK1
WK2
WK3
WK4
D-28 to -1
D1
D2
D3
D4
D5
D6
D7
D8
D15
D22
D28c
Study Entry (Section 6.1)
Informed consent 
X
Inclusion/ exclusion criteria
X
Medicalt/ oncologic history 
X
AML or MDS Disease 
Assessment and Cohort 
Assignmentb
X
Demographics 
X
IRT registration
X
X
Pregnancy risk counseling and 
contraceptive compliance 
confirmation
X
As specified in Section 6.1.1 and the PPP in Appendix L
Prior/ concomitant medications & 
procedures (Section 6.2.1)
X
X
X
X
X
X
X
X
X
X
X
CC-90009 Administration (Section 7)
Calcium, calcitriol, and vitamin D 
supplements and recording on 
diary card (refer to Section 7.2)
X (D-3 to D-1)
X
X
X
X
X
X
X
Xd
Provide/review diary card
X
X
Corticosteroid administration 
(dexamethasone) (refer to 
Section 7.2) for doses 3.6 mg and 
above
X
X
X
X
X
X
X
IV administration of CC-90009
X
X
X
X
X
X
X
1.0
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Table 35:
Table of Events for Part B (D1-7 Schedule) of Cycle 1
Eventsa
Screening
Treatment Period
Cycle 1
WK1
WK2
WK3
WK4
D-28 to -1
D1
D2
D3
D4
D5
D6
D7
D8
D15
D22
D28c
Monitoring as an inpatient
X
X
X
X
X
X
X
Safety Assessments (Section 6)
Adverse Event Evaluation 
(Section 6.2.2)
X
X
X
X
X
X
X
X
X
X
X
Height
X
Weight (Section 6.2.3)
X
X
X
X
X
Vital Signs (Section 6.2.3)
X
Xf
Xf
Xf
Xf
Xf
Xf
Xf
X
X
X
Physical Examination 
(Section 6.2.4)
X
X
X
ECOG PS (Appendix D)
X
X
X
SARS-CoV-2 Viral Testingr
X (within 7 
days of D1)
12-lead ECG (in triplicate, 
Section 6.2.5)
X (≥72 hrs 
prior to D1)
Xf
Xf
X
Adverse Event Evaluation 
(Section 6.2.2)
X
X
X
X
X
X
X
X
X
X
X
Height
X
Weight (Section 6.2.3)
X
X
X
X
X
Vital Signs (Section 6.2.3)
X
Xf
Xf
Xf
Xf
Xf
Xf
Xf
X
X
X
Physical Examination 
(Section 6.2.4)
X
X
X
Safety Assessments (Section 6)
ECOG PS (Appendix D)
X
X
X
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Table 35:
Table of Events for Part B (D1-7 Schedule) of Cycle 1
Eventsa
Screening
Treatment Period
Cycle 1
WK1
WK2
WK3
WK4
D-28 to -1
D1
D2
D3
D4
D5
D6
D7
D8
D15
D22
D28c
12-lead ECG (in triplicate, 
Section 6.2.5)
X (≥72 hrs 
prior to D1)
Xf
Xf
X
LVEF (ECHO/MUGA scan; 
Section 6.2.6)
X
Pregnancy testing per PPP (FCBP 
only; Section 6.2.7)
Xg
X
X
X
Hematology laboratory tests 
(Section 6.2.8)
X (D-14 to -1)
X
X
X
X
X
X
X
X
X
X
G6PD (Section 6.2.8)
X
Serum chemistry laboratory tests 
(Section 6.2.8)h
X
(D-3 to -1)
Xi
Xi
Xi
X
X
X
X
X
X
X
Additional serum Ca, Mg and 
PTH tests (Section 6.2.8)h
Xj
Xj
Xj
Xj
Xj
Xj
Xj
Serum 25-hydroxyvitamin D level 
(Section 6.2.8)
X
X
Serum PTH, P1NP, β-CTx tests
Urine Ca/ creatinine ratio 
(random) (Section 6.2.8)
X
X
X
X
Amylase, lipase, T-cell subsets 
(CD4+ and CD8+), TSH 
(Section 6.2.8)
X
PT, INR, PTT (Section 6.2.8)k
X
Urinalysis (Section 6.2.8)
X (D-14 to -1)
X
PK & PD Assessments
Blood, PK (Section 6.5)
Xl
X
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Table 35:
Table of Events for Part B (D1-7 Schedule) of Cycle 1
Eventsa
Screening
Treatment Period
Cycle 1
WK1
WK2
WK3
WK4
D-28 to -1
D1
D2
D3
D4
D5
D6
D7
D8
D15
D22
D28c
Pharmacogenomics sample (eg, 
buccal cells or nail clippings), 
(Section 6.6.1)
X
SARS-CoV-2 serologys
(Section 6.6.4)
X
Blood (whole), biomarker flow 
cytometry (Section 6.6.2)
X (D-14 to -1)
Xl
Xl
X
X
Blood (whole), PD biomarker 
(Section 6.6.2)
X (D-14 to -1)
Xn
X 
(± 3d)
Blood (PBMCs), PD protein and 
RNA (Section 6.6.2)
X (D-14 to -1)
X
X
X
Blood (PBMCs), PD ex vivo 
sensitivity assays, phenotyping & 
sequencing (Section 6.6.2)
X
Blood (plasma), PD cytokines 
(Section 6.6.2
X (D-14 to -1)
X
X
X
X
X
Bone marrow aspirate and biopsy, 
PD biomarkers & MRD (Section 
6.6.3)m
X (D-14 to -1)
Xn
X 
(± 3d)
Efficacy
Bone marrow aspiration and 
biopsy, complete blood counts 
and examination of peripheral 
blood smears (Section 6.4)o
X (D-14 to -1)p
X 
(± 3d)
Abbreviations:  β-CTx = beta C-terminal telopeptide; C = cycle; Ca = calcium; CD = cluster of differentiation; D = day; ECHO = echocardiogram; ECG = electrocardiogram; ECOG 
PS = Eastern Cooperative Oncology Group performance status; FCBP = females of child bearing potential; G6PD = glucose-6-phosphate dehydrogenase; hrs = hours; INR = 
international normalized ratio; IRT = integrated response technology; IV = intravenous; LVEF = left ventricular ejection fraction; Mg = magnesium; MRD = Minimal Residual 
Disease; MUGA = multi-gated acquisition scan; P1NP = procollagen type 1 N-terminal propeptide; PBMC = peripheral blood mononuclear cells; PD =pharmacodynamics; PK = 
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pharmacokinetic; PPP = pregnancy prevention plan; PT = prothrombin time; PTH = parathyroid hormone; PTT = partial thromboplastin time; RNA = ribonucleic acid; RT-PCR = 
reverse transcriptase polymerase chain reaction; SARS-CoV-2 = severe acute respiratory syndrome coronavirus; TSH = thyroid-stimulating hormone; WK = week. 
a All study visits/procedures will have a ± 2 day window and all laboratory blood samples should be drawn predose (≤ 5 hrs), unless otherwise specified in this table or Section 
6.
b See Section 6.1 for details regarding collecting BMA/BMB, PBS, and cytogenetics at screening for assessing AML/MDS diagnosis, for potential retrospective confirmation 
of mutational status, and collecting BMA and PB at screening for pharmacodynamics and correlative studies. A bone marrow biopsy can be collected in conjunction with an 
aspirate if it is standard institutional practice.  A bone marrow biopsy must be collected if adequate aspirate sample is not attainable.
c Eligible subjects continue on to Cycle 2 (refer to Table 36).  
d Supplementation may be prolonged if hypocalcemia occurs (refer to Section 7.2.13.2). Subjects are to start supplements at least 3 days prior to Day 1 of Cycle 2 as per 
Section 7.2.
e Subjects will be closely monitored during administration of CC-90009 and for at least one hour after. Subjects should be adequately hydrated to prevent potential tumor lysis 
syndrome (TLS) (eg, 2 to 3 liters of oral or IV fluids per day) starting the day prior to CC-90009 administration and continuing through each day of CC-90009 
administration. Refer to Section 7.2.12 for information on dose interruptions. The SRC may decide to evaluate alternate dosing schedules (eg, increasing from 5 to up to 
10 consecutive days of CC-90009 administration) based on their review of available clinical and laboratory safety data, PK profiles, and PD findings. 
f Multiple measurements performed on this day. 
g Two pregnancy tests (sensitivity of at least 25 mIU/mL) must be performed prior to first dose of CC-90009:  within 10 to 14 days prior and within 24 hours prior. Both tests 
must be negative for CC-90009 dosing to begin. 
h A free (ionized) serum calcium test should be obtained at Screening to establish baseline values in addition to the corrected serum calcium test (corrected for albumin) used to 
fulfill the inclusion criteria. In the event of Grade ≥ 2 hypocalcemia or symptoms of hypocalcemia (eg, carpopedal spasm, tetany, seizures, etc), subjects must be hospitalized. 
Also, if Grade ≥ 2 hypocalcemia and abnormal levels of serum albumin occurs, a serum ionized calcium test must be performed. Refer to Section 7.2.13.2 for hypocalcemia 
management guidelines.
i
Specific tests for TLS monitoring required predose and 12 hours (± 1 hour) postdose on Days 1, 2, and 3. Refer to Section 6.2.8. 
j
Additional serum calcium/magnesium tests required 6 and 12 hours (± 1 hour) postdose on days of CC-90009 administration. Additional PTH tests required at 6 hours (± 1 
hours) post-dose on days of CC-90009 administration.
k Subsequent coagulation tests only performed for subjects on anticoagulant therapy and as clinically indicated. 
l
Multiple blood samples will be collected for this assay on the specified day. Refer to Sections 6.5 and 6.6.
m Bone marrow samples for biomarker assessment are mandatory. If bone marrow samples are scheduled to be collected on the same day for efficacy, the biomarker samples 
should be collected at the same time. If sufficient bone marrow aspirate specimen is not available, peripheral blood may be submitted in place of the BMA specimen for 
biomarker studies (eg, MRD); see laboratory manual for details.
n Obtained between 4 to 8 hours postdose. The samples may be obtained on Day 6 or on Day 8 if necessary due to scheduling difficulties. If the dosing interval (schedule) is 
extended, then samples will be obtained on the last day ±1 day of dosing (eg, if extended to 10 day, obtain on Day 9-11).
o Additional aspirates and biopsies will be collected as clinically indicated (eg, Cycle 1 Day 15 based on Investigator’s medical assessment). 
p Molecular and cytogenetic studies may be omitted at:  Screening, if they were completed within the previous 90 days and the results are available for recording on the electronic 
case report forms; see Section 6.1 for details on sending samples to the central laboratory.  
q
Urine PK to be performed on approximately 10 selected subjects from Part A and/or Part B.  This is a 24-hour collection that starts C1D1 and ends C1D2.
r
RT-PCR testing for SARS-CoV-2 is mandatory within 7 days prior to first dose of CC-90009 (C1D1). The RT-PCR test should be based on institutional or local guidelines. 
Please see Section 6.1 in the event of a positive result.
s
Serum will be collected at predose on Cycle 1 Day 1 (or at screening), approximately every 6 months during study treatment and at EOT to be used for possible measurements 
of anti-SARS-CoV-2 serology (anti-SARS-CoV-2 total or IgG). Results will not be used to determine eligibility. Serum should also be collected approximately 4 weeks after 
a documented or suspected SARS-CoV-2 infection.
t   Medical history will also include COVID-19 vaccines, toxicities of prior treatments, and known allergies. 
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175
Table 36:
Table of Events for Part B (D1-7 Schedule) of Cycles ≥ 2
Eventsa
Treatment Period
Follow-up Period
Cycles ≥ 2
EOTb
Safetyc
Long 
Term
WK1
WK2
WK3
WK4
D1
D2
D3
D4
D5
D6
D7
D8
D15
D22
D28
≤ 28 
days
28 days 
(± 3 days)
Review concomitant medications 
& procedures (Section 6.2.1)
X
X
X
X
X
X
X
X
X
X
X
X
X
CC-90009 Administration (Section 7)
Calcium, calcitriol and Vitamin 
D supplements and recording on 
diary card (Section 7.2)
X
X 
X 
X 
X 
X 
X
Xd
X (C2 and 
C3)d
Provide/ review of diary card
X
X
Corticosteroid administration 
(dexamethasone) (refer to 
Section 7.2) for doses 3.6 mg 
and above
X
X
X
X
X
X
X
IV administration of CC-90009e
X
X
X
X
X
X
X
Safety Assessments (Section 6)
Adverse Event Evaluation 
(Section 6.2.2)
X
X
X
X
X
X
X
X
X
X
X
X
Weight (Section 6.2.3)
X
X
Vital Signs (Section 6.2.3)
Xf
Xf
Xf
Xf
Xf
Xf
Xf
X
X
X
X
Physical Examination (Section 
6.2.4)
X
X
ECOG PS (Appendix D)
X
X
12-lead ECG (Section 6.2.5)g
X
X
LVEF (ECHO/MUGA; Section 
6.2.6)
X (only 
C2 ± 7d)
X (± 7d)h
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Table 36:
Table of Events for Part B (D1-7 Schedule) of Cycles ≥ 2
Eventsa
Treatment Period
Follow-up Period
Cycles ≥ 2
EOTb
Safetyc
Long 
Term
WK1
WK2
WK3
WK4
D1
D2
D3
D4
D5
D6
D7
D8
D15
D22
D28
≤ 28 
days
28 days 
(± 3 days)
Pregnancy risk counseling and 
contraceptive compliance 
confirmation
X
As specified in Section 6.1.1 and the PPP in Appendix L
Pregnancy test (FCBP only; 
Section 6.2.7) 
X
Xi
Xi
Xi
Hematology laboratory (Section 
6.2.8)
X
X
X
X
X
X
X
X
X
X
X
Serum chemistry laboratory tests 
(Section 6.2.8)j
X
X
X
X
X
X
Serum Ca & Mg tests  
(Section 6.2.8)j
Xj
Xj
Xj
Xj
Xj
Xj
Xj
Serum PTH, P1NP, β-CTx tests 
(Section 6.2.8)
X
X
X
Serum 25-hydroxyvitamin D 
level (Section 6.2.8)
X
Urine Ca/ creatinine ratio test 
(random) (Section 6.2.8)
X
X
X
Amylase, lipase, T-cell subsets 
(CD4+ and CD8+), TSH 
(Section 6.2.8)
X
X
PT, INR, PTT (for subjects on 
anticoagulant therapy) 
(Section 6.2.8)
X
X
Urinalysis (Section 6.2.8)
X
X
PK & PD Assessments
Blood, PK (Section 6.5)o
Xo
Xo
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Final: 31 Mar 2022
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Table 36:
Table of Events for Part B (D1-7 Schedule) of Cycles ≥ 2
Eventsa
Treatment Period
Follow-up Period
Cycles ≥ 2
EOTb
Safetyc
Long 
Term
WK1
WK2
WK3
WK4
D1
D2
D3
D4
D5
D6
D7
D8
D15
D22
D28
≤ 28 
days
28 days 
(± 3 days)
Blood (whole), PD biomarker 
(Section 6.6.2)
X (C2 and 
C4; ± 3d)
Xn
Refer 
to 
Section 
6.3.2
Bone marrow aspirate and 
biopsy, PD biomarkers & MRD 
(Section 6.6.3)l, m
X (C2 and 
C4; ± 3d)
Xn
Refer 
to 
Section 
6.3.2
SARS-CoV-2 Serologyp
(Section 6.6.4)
Serum collected every 6 months during study treatment (eg, C6D1, C12D1, etc)
X
Efficacy
Complete blood counts and 
examination of peripheral blood 
smears (Section 6.4)m
X (C2 and 
C4; ± 3d)
Xn
Refer 
to 
Section 
6.3.2
Bone marrow aspirate and/or 
biopsy (Section 6.4)m
X (C2 and 
C4; ± 3d)
Xn
Refer 
to 
Section 
6.3.2
Follow-up
CC-90009-related AE/SAE 
follow-up
Refer to Section 6.3.1
Anticancer therapies 
Refer to Section 6.3.2
Survival 
Refer to Section 6.3.3
Transformation to AML for 
MDS 
After signing ICF and until death, lost to follow-up, withdrawal of consent for further data collection, or end of trial.
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Abbreviations:  Adverse event = AE; AML = acute myeloid leukemia; β-CTx = beta C-terminal telopeptide; C = cycle; Ca = calcium; CD = cluster of differentiation; D = day; 
ECHO = echocardiogram; ECG = electrocardiogram; ECOG PS = Eastern Cooperative Oncology Group performance status; EOT = End of Treatment; FCBP = females of child 
bearing potential; INR = international normalized ratio; IV = intravenous; LVEF = left ventricular ejection fraction; MDS = myelodysplastic syndromes; Mg = magnesium; MUGA 
= multi-gated acquisition scan; P1NP = procollagen type 1 N-terminal propeptide; PD = pharmacodynamic; PK = pharmacokinetic; PPP = pregnancy prevention plan; PT = 
prothrombin time; PTH = parathyroid hormone; PTT = partial thromboplastin time; q = every; SAE = serious adverse event; TSH = thyroid-stimulating hormone; WK = week. 
a All study visits/procedures will have a ± 2 day window and all laboratory blood samples should be drawn predose (≤ 5 hrs), unless otherwise specified in this table or Section 6. 
Cycles should start ≤ 7 days after the last day of the previous cycle. 
b EOT Visit performed within 28 days after last dose of CC-90009 for subjects that discontinue prior to completing dosing in Cycle 4. For subjects that complete dosing in Cycle 4, 
this visit should be completed on Day 28 (± 2 days) of Cycle 4.  For subjects who complete dosing after Cycle 4, EOT Visit should be completed within 28 days after the last day 
of the previous cycle. 
c Safety Follow-up Visit is performed 28 days (± 3 days) after the last dose of CC-90009 for all subjects. May be performed by telephone contact if pregnancy testing is not required 
(refer to footnote “i”). 
d Supplements to be administered for at least 3 days after the last dose in each cycle. Supplementation may be prolonged if hypocalcemia occurs (refer to Section 7.2.13.2). Subjects 
to start supplements at least 3 days prior to Day 1 of Cycles 3 and 4 as per Section 7.2.
e Subjects will be closely monitored during the administration of CC-90009 and for at least 1 hour after. Subjects should be adequately hydrated to prevent potential tumor lysis 
syndrome (TLS) (eg, 2 to 3 liters of oral or IV fluids per day) starting the day prior to CC-90009 administration and continuing through each day of CC-90009 administration. Refer 
to Section 7.2.12 for information on dose interruptions. The SRC may decide to evaluate alternate dosing schedules (eg, increasing from 5 to up to 10 consecutive days of CC-
90009 administration) based on their review of available clinical and laboratory safety data, PK profiles, and PD findings. Subjects should be administered Cycle ≥ 2 of CC-90009 
in a Limited Stay Unit (LSU) or as in patient. Subjects experiencing Grade ≥ 2 hypocalcemia during any cycle should be administered CC-90009 in the inpatient setting for 
subsequent cycles (an exception can be made for subjects with grade 2 hypocalcemia lasting less than 24 hours that recovers without IV calcium [eg, calcium gluconate or calcium 
chloride] after discussion with the Celgene medical monitor).
f Multiple measurements performed on this day. For subjects who are administered as in-patient in Cycles ≥ 2, on days that CC-90009 is administered, vital signs will be obtained 
prior to dosing (≤3 hours), and 60 minutes (± 15 minutes) and 6 hours (± 1 hr) after the end of the administration of the dose. Starting in Cycle 2 in the outpatient setting, vital 
signs will be obtained prior to dosing (≤3 hours) and at 60 minutes (± 15 minutes) after the end of the administration of the dose. Additional vital signs should be obtained as 
clinically indicated per the Investigator’s medical assessment.
g Triplicate ECGs will be performed on Day 1 of each cycle (refer to Section 6.2.5) and a single ECG obtained at the EOT visit. 
h The EOT Visit LVEF is not required if the prior LVEF was performed within 56 days. 
i
Per the PPP, a pregnancy test is required 28 days after the last dose of for all FCBP. For FCBP with irregular menstrual periods, a pregnancy test is required every 14 days (ie, 
Day 15 of Cycles ≥ 2 and at 14 and 28 days after the last dose of CC-90009).
j
In the event of Grade ≥ 2 hypocalcemia or symptoms of hypocalcemia (eg, carpopedal spasm, tetany, seizures, etc), subjects must be hospitalized. Also, if Grade ≥ 2 hypocalcemia 
and abnormal levels of serum albumin occurs, a serum ionized calcium test must be performed. Refer to Section 7.2.13.2 for hypocalcemia management guidelines. Refer to 
Section 6.2.8 for required days and timing of tests. Subjects who experienced Grade ≥ 2 hypocalcemia during Cycle 1, require testing Days 1-7 at 6 and 12 hours postdose. All 
other subjects require testing prior to dosing. 
k If intra-subject dose escalation occurs, blood samples for PD assays will be collected during the first cycle only at the increased dose; see laboratory manual for details. Multiple 
blood samples will be collected for this assay on the specified Days 1, 2, 5. Refer to Section 6.6. 
l
Bone marrow samples for biomarker PD assessment are mandatory. When applicable (refer to time points in the table above), bone marrow samples for biomarker PD assessment 
will be obtained at the same time as a scheduled efficacy assessment. If sufficient bone marrow aspirate specimen is not available, peripheral blood may be submitted in place of 
the BMA specimen for biomarker studies (eg, MRD); see laboratory manual for details. A bone marrow biopsy can be collected in conjunction with an aspirate if it is standard 
institutional practice.  A bone marrow biopsy must be collected if adequate aspirate sample is not attainable; see for details on sending samples to the central laboratory for disease 
assessment.
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Final: 31 Mar 2022
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m If end of Cycle 2 (Day 28 ± 3 days) samples are obtained on Day 1 of Cycle 3, they must be obtained prior to CC-90009 administration. Additionally, bone marrow aspirates and 
biopsies may be obtained after a CR is confirmed, if relapse is suspected, or following treatment discontinuation to elucidate effects of long-term treatment or resistance 
mechanisms. Additional aspirates and biopsies will be collected as clinically indicated based on the Investigator’s medical assessment.
n
For subjects that complete dosing in Cycle 4, performed/obtained once on Day 28 (± 3 days). For subjects that continue (after consultation with Medical Monitor) beyond Cycle 
4, efficacy and bone marrow PD assessments may be obtained to confirm a CR, if relapse is suspected, or following treatment discontinuation to elucidate effects of long-term 
treatment or resistance mechanisms. Additional aspirates and biopsies will be collected as clinically indicated based on the Investigator’s medical assessment. Refer to Section 
6.3.2 and Section 6.4.
o Predose blood sample for both intensive and sparse sampling schedule in Cycles 2-4. Refer to Sections 6.5 and 6.6.
p Serum will be collected approximately every 6 months during study treatment and at EOT to be used for possible measurements of anti-SARS-CoV-2 serology (anti-SARS-CoV-
2 total or IgG). Serum should also be collected approximately 4 weeks after a documented or suspected SARS-CoV-2 infection. 
1.0
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Final: 31 Mar 2022
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Appendix O:
Part A Table of Events for D1-10 Dosing Schedule
Table 37:
Table of Events for Part A (D1-10 Schedule) of Cycle 1
Screening
Treatment Period
Cycle 1
WK1
WK2
WK3
WK4
WK5b
WK6b
Eventsa
D-28 to -1
D1
D2
D3
D4
D5
D6
D7
D8
D9
D10
D15
D22
D28c
D29
D36
Study Entry (Section 6.1)
Informed consent 
X
Inclusion/ exclusion criteria
X
Medical/ oncologic history 
X
Demographics 
X
IRT registration
X
X
Pregnancy risk counseling and 
contraceptive compliance 
confirmation
X
As specified in Section 6.1.1 and the PPP in Appendix L
Prior/ concomitant medications 
& procedures (Section 6.2.1)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
CC-90009 Administration (Section 7)
Calcium, calcitriol, and vitamin 
D supplements and recording on 
diary card (refer to Section 7.2)
X (D-3 to 
D-1)
X
X
X
X
X
X
X
X
X
Xd
Xd
Xd
Provide/ review diary card
X
X
Corticosteroid administration 
(dexamethasone) 
(refer to Section 7.2) for doses 
3.0 mg and above
X
X
X
X
X
X
X
X
X
X
IV administration of CC-90009e
X
X
X
X
X
X
X
X
X
X
Monitoring as inpatient 
X
X
X
X
X
X
X
X
X
X
Safety Assessments (Section 6)
Adverse Event Evaluation 
(Section 6.2.2)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Height
X
1.0
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Final: 31 Mar 2022
181
Table 37:
Table of Events for Part A (D1-10 Schedule) of Cycle 1
Screening
Treatment Period
Cycle 1
WK1
WK2
WK3
WK4
WK5b
WK6b
Eventsa
D-28 to -1
D1
D2
D3
D4
D5
D6
D7
D8
D9
D10
D15
D22
D28c
D29
D36
Weight (Section 6.2.3)
X
X
X
X
X
Vital Signs (Section 6.2.3)
X
Xf
Xf
Xf
Xf
Xf
Xf
Xf
Xf
Xf
Xf
X
X
X
X
Physical Examination 
(Section 6.2.4)
X
X
X
ECOG PS (Appendix D)
X
X
X
12-lead ECG (in triplicate, 
Section 6.2.5)
X (≥72 hrs 
prior to 
D1)
Xf
X
Xf
LVEF (ECHO/MUGA scan; 
Section 6.2.6)
X
Pregnancy testing per PPP 
(FCBP only; Section 6.2.7)
Xg
X
X
X
X
Hematology laboratory tests 
(Section 6.2.8)
X (D-14 
to -1)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
G6PD (Section 6.2.8)
X
Serum chemistry laboratory tests 
(Section 6.2.8)h
X
(D-3 
to -1)
Xi
Xi
Xi
X
X
X
X
X
X
X
X
X
X
X
Additional serum Ca, Mg and 
PTH tests (Section 6.2.8)h
Xj
Xj
Xj
Xj
Xj
Xj
Xj
Xj
Xj
Xj
Serum PTH, P1NP, β-CTx tests 
(Section 6.2.8)
X
X
X
X
Serum 25-hydroxyvitamin D 
level (Section 6.2.8)
X
X
Urine Ca/ creatinine ratio 
(random) (Section 6.2.8)
X
X
X
X
1.0
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CC-90009-AML-001 Amendment 9
Final: 31 Mar 2022
182
Table 37:
Table of Events for Part A (D1-10 Schedule) of Cycle 1
Screening
Treatment Period
Cycle 1
WK1
WK2
WK3
WK4
WK5b
WK6b
Eventsa
D-28 to -1
D1
D2
D3
D4
D5
D6
D7
D8
D9
D10
D15
D22
D28c
D29
D36
Amylase, lipase, T-cell subsets 
(CD4+ and CD8+), TSH 
(Section 6.2.8)
X
PT, INR, PTT (Section 6.2.8)k
X
Urinalysis (Section 6.2.8)
X
(D-14 
to -1)
X
PK & PD Assessments
Blood, PK (Section 6.5)
Xl
X
Xl
X
Xl
Urine, PK (Section 6.5) selected 
subjectsr
X
Pharmacogenomics sample (eg, 
buccal cells or nail clippings), 
(Section 6.6.1)
X
Blood (whole), biomarker flow 
cytometry (Section 6.6.2)
X
(D-14 
to -1)
Xl
Xl
Xl
X
X
Blood (PBMCs), PD protein and 
RNA (Section 6.6.2)
X
(D-14 
to -1)
Xl
X
X
X
Blood (PBMCs), PD ex vivo 
sensitivity assays, phenotyping & 
sequencing (Section 6.6.2)
X
Blood (plasma), PD cytokines 
(Section 6.6.2)
X
(D-14 
to -1)
X
X
X
X
X
Bone marrow aspirate and 
biopsy, PD biomarkers & MRD 
(Section 6.6.3)m
X
(D-14 
to -1)
Xn
X 
(± 3d)
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Table 37:
Table of Events for Part A (D1-10 Schedule) of Cycle 1
Screening
Treatment Period
Cycle 1
WK1
WK2
WK3
WK4
WK5b
WK6b
Eventsa
D-28 to -1
D1
D2
D3
D4
D5
D6
D7
D8
D9
D10
D15
D22
D28c
D29
D36
Efficacy
Bone marrow aspiration and 
biopsy, complete blood counts 
and examination of peripheral 
blood smears (Section 6.4)o
X 
(D-14 
to -1)p
X 
(± 3d)
X 
(only 
on 
D42 
± 3d)q
Abbreviations:  β-CTx = beta C-terminal telopeptide; C = cycle; Ca = calcium; CD = cluster of differentiation; D = day; ECHO = echocardiogram; ECG = electrocardiogram; 
ECOG PS = Eastern Cooperative Oncology Group performance status; FCBP = females of child bearing potential; G6PD = glucose-6-phosphate dehydrogenase; hrs = hours; INR 
= international normalized ratio; IRT = integrated response technology; IV = intravenous; LVEF = left ventricular ejection fraction; Mg = magnesium; MRD = Minimal Residual 
Disease; MUGA = multi-gated acquisition scan; P1NP = procollagen type 1 N-terminal propeptide; PBMC = peripheral blood mononuclear cells; PD = pharmacodynamic; PK = 
pharmacokinetic; PPP = pregnancy prevention plan; PT = prothrombin time; PTH = parathyroid hormone; PTT = partial thromboplastin time; RNA = ribonucleic acid; TSH = 
thyroid-stimulating hormone; WK = week. 
a All study visits/procedures will have a ± 2 day window and all laboratory blood samples should be drawn predose (≤ 5 hrs), unless otherwise specified in this table or Section 
6.
b Subjects with hypoplastic bone marrow without evidence of persistent AML at the Day 28 assessment who have Grade ≥ 3 neutropenia will be followed for an additional 
2 weeks for safety monitoring in Cycle 1 (total duration of 42 days; refer to Figure 1). Not all visits are shown as separate columns under Week 6, ie, Day 42 bone marrow 
assessment. 
c Eligible subjects continue on to Cycle 2 (refer to Table 5).  Based on the Day 28 bone marrow evaluation, subjects with a hypoplastic bone marrow without evidence of 
persistent leukemia who have Grade ≥ 3 neutropenia will be followed for an additional 2 weeks for safety monitoring in Cycle 1. 
d Supplementation may be prolonged if hypocalcemia occurs (refer to Section 7.2.13.2). Subjects are to start supplements at least 3 days prior to Day 1 of Cycle 2 as per 
Section 7.2.
e Subjects will be closely monitored during administration of CC-90009 and for at least one hour after. Subjects should be adequately hydrated to prevent potential tumor lysis 
syndrome (TLS) (eg, 2 to 3 liters of oral or IV fluids per day) starting the day prior to CC-90009 administration and continuing through each day of CC-90009 
administration. Refer to Section 7.2.12 for information on dose interruptions. The SRC may decide to evaluate alternate dosing schedules (eg, increasing from 5 to up to 
10 consecutive days of CC-90009 administration) based on their review of available clinical and laboratory safety data, PK profiles, and PD findings. 
f Multiple measurements performed on this day. 
g Two pregnancy tests (sensitivity of at least 25 mIU/mL) must be performed prior to first dose of CC-90009:  within 10 to 14 days prior and within 24 hours prior. Both tests 
must be negative for CC-90009 dosing to begin. 
h A free (ionized) serum calcium test should be obtained at Screening to establish baseline values in addition to the corrected serum calcium test (corrected for albumin) used to 
fulfill the inclusion criteria. In the event of Grade ≥ 2 hypocalcemia or symptoms of hypocalcemia (eg, carpopedal spasm, tetany, seizures, etc), subjects must be hospitalized. 
Also, if Grade ≥ 2 hypocalcemia and abnormal levels of serum albumin occurs, a serum ionized calcium test must be performed. Refer to Section 7.2.13.2 for hypocalcemia 
management guidelines.
i
Specific tests for TLS monitoring required predose and 12 hours (± 1 hour) postdose on Days 1, 2, and 3. Refer to Section 6.2.8. 
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j
Additional serum calcium/magnesium tests required 6 and 12 hours (± 1 hour) postdose on days of CC-90009 administration. Additional PTH tests required at 6 hours (± 1 
hours) post-dose on days of CC-90009 administration.
k Subsequent coagulation tests only performed for subjects on anticoagulant therapy and as clinically indicated. 
l
Multiple blood samples will be collected for this assay on the specified day. Refer to Sections 6.5 and 6.6.
m Bone marrow samples for biomarker assessment are mandatory. If bone marrow samples are scheduled to be collected on the same day for efficacy, the biomarker samples 
should be collected at the same time. If sufficient bone marrow aspirate specimen is not available, peripheral blood may be submitted in place of the BMA specimen for 
biomarker studies (eg, MRD); see laboratory manual for details.
n Obtained between 4 to 8 hours postdose. The samples may be obtained on Day 6 or Day 8 if necessary due to scheduling difficulties. If the dosing interval (schedule) is 
extended, then samples will be obtained on the last day ±1 day of dosing (eg, if extended to 10 day, obtain on Day 9-11).
o Additional aspirates and biopsies will be collected as clinically indicated (eg, Cycle 1 Day 15 based on Investigator’s medical assessment). 
p Molecular and cytogenetic studies may be omitted at:  Screening, if they were completed within the previous 90 days and the results are available for recording on the electronic 
case report forms and Day 42 (or at hematologic recovery), if a complete response is documented at Day 28.  
q Additional bone marrow assessment performed at the time of hematologic recovery or Day 42 (± 3 days).  Eligible subjects continue on to Cycle 2 (refer to Table 5).
r Urine PK to be performed on approximately 10 selected subjects from Part A and/or Part B. This is a 24-hour collection that starts on C1D1 and ends on C1D2. 
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Table 38:
Table of Events for Part A (D1-10 Schedule) of Cycles ≥ 2
Treatment Period
Follow-up Period
Cycles ≥ 2
WK1
WK2
WK3
WK4
EOTb
Safetyc
Eventsa
D1
D2
D3
D4
D5
D6
D7
D8
D9
D10
D15
D22
D28
≤ 28 
days
28 days 
(± 3 days)
Long 
Term
Review concomitant medications & 
procedures (Section 6.2.1)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
CC-90009 Administration 
(Section 7)
Calcium, calcitriol and Vitamin D 
supplements and recording on diary 
card (Section 7.2)
X
X
X
X
X
X
X
X
X
Xd
X (C2 
and 
C3)d
Provide/ review of diary card
X
X
Corticosteroid administration 
(dexamethasone) (refer to 
Section 7.2) for doses 3.0 mg and 
above
X
X
X
X
X
X
X
X
X
X
IV administration of CC-90009e
X
X
X
X
X
X
X
X
X
X
Safety Assessments (Section 6)
Adverse Event Evaluation (Section 
6.2.2)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Weight (Section 6.2.3)
X
X
Vital Signs (Section 6.2.3)
Xf
Xf
Xf
Xf
Xf
Xf
Xf
Xf
Xf
Xf
X
X
X
Physical Examination (Section 
6.2.4)
X
X
ECOG PS (Appendix D)
X
X
12-lead ECG (Section 6.2.5)g
X
X
LVEF (ECHO/MUGA; Section 
6.2.6)
X 
(only 
C2 ± 
7d)
X 
(± 7d)h
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Table 38:
Table of Events for Part A (D1-10 Schedule) of Cycles ≥ 2
Treatment Period
Follow-up Period
Cycles ≥ 2
WK1
WK2
WK3
WK4
EOTb
Safetyc
Eventsa
D1
D2
D3
D4
D5
D6
D7
D8
D9
D10
D15
D22
D28
≤ 28 
days
28 days 
(± 3 days)
Long 
Term
Pregnancy test (FCBP only; 
Section 6.2.7) 
X
Xi
Xi
Xi
Pregnancy risk counseling and 
contraceptive compliance 
confirmation 
X
As specified in Section 6.1.1 and the PPP in Appendix L
Hematology laboratory (Section 
6.2.8)
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum chemistry laboratory tests 
(Section 6.2.8)j
X
X
X
X
X
X
Serum Ca & Mg tests 
(Section 6.2.8)j
Xj
Xj
Xj
Xj
Xj
Xj
Xj
Xj
Xj
Xj
Serum PTH, P1NP, β-CTx tests 
(Section 6.2.8)
X
X
X
Serum 25-hydroxyvitamin D level 
(Section 6.2.8)
X
Urine Ca/ creatinine ratio test 
(random) (Section 6.2.8)
X
X
X
Amylase, lipase, T-cell subsets 
(CD4+ and CD8+), TSH 
(Section 6.2.8)
X
X
PT, INR, PTT (for subjects on 
anticoagulant therapy) 
(Section 6.2.8)
X
X
Urinalysis (Section 6.2.8)
X
X
PK & PD Assessments
Blood, PK (Section 6.5)o
X
X
X
X
Xo
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Final: 31 Mar 2022
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Table 38:
Table of Events for Part A (D1-10 Schedule) of Cycles ≥ 2
Treatment Period
Follow-up Period
Cycles ≥ 2
WK1
WK2
WK3
WK4
EOTb
Safetyc
Eventsa
D1
D2
D3
D4
D5
D6
D7
D8
D9
D10
D15
D22
D28
≤ 28 
days
28 days 
(± 3 days)
Long 
Term
Blood (whole), biomarker flow 
cytometry, (Section 6.6.2) first 
cycle of intra-subject dose 
escalation onlyk
Xk
Xk
Xk
Xk
Xk
Blood (PBMCs), PD protein and 
RNA (Section 6.6.2) first cycle of 
intra-subject dose escalation onlyk
Xk
Xk
Xk
Xk
Blood (plasma), PD cytokines 
(Section 6.6.2) first cycle of intra-
subject dose escalation onlyk
X
X
X
X
X
Bone marrow aspirate and biopsy, 
PD biomarkers & MRD (Section 
6.6.3)l, m
X (C2 
and 
C4; ± 
3d)
Xn
Refer to 
Section 
6.3.2
Efficacy
Complete blood counts and 
examination of peripheral blood 
smears (Section 6.4)m
X (C2 
and 
C4; ± 
3d)
Xn
Refer to 
Section 
6.3.2
Bone marrow aspirate and biopsy 
(Section 6.4)m
X (C2 
and 
C4; ± 
3d)
Xn
Refer to 
Section 
6.3.2
Follow-up 
CC-90009-related AE/SAE follow-
up
Refer to Section 6.3.1
Anticancer therapies 
Refer to Section 6.3.2
Survival 
Refer to Section 6.3.3
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Abbreviations:  Adverse event = AE; β-CTx = beta C-terminal telopeptide; C = cycle; Ca = calcium; CD = cluster of differentiation; D = day; ECHO = echocardiogram; ECG = 
electrocardiogram; ECOG PS = Eastern Cooperative Oncology Group performance status; EOT = End of Treatment; FCBP = females of child bearing potential; INR = international 
normalized ratio; IV = intravenous; LVEF = left ventricular ejection fraction; Mg = magnesium; MUGA = multi-gated acquisition scan; P1NP = procollagen type 1 N-terminal 
propeptide; PD = pharmacodynamics; PPP = pregnancy prevention plan; PT = prothrombin time; PTH = parathyroid hormone; PTT = partial thromboplastin time; q = every; SAE 
= serious adverse event; TSH = thyroid-stimulating hormone; WK = week. 
a All study visits/procedures will have a ± 2 day window and all laboratory blood samples should be drawn predose (≤ 5 hrs), unless otherwise specified in this table or Section
6. Cycles should start ≤ 7 days after the last day of the previous cycle. 
b EOT Visit performed within 28 days after last dose of CC-90009 for subjects that discontinue prior to completing dosing in Cycle 4. For subjects that complete dosing in Cycle 
4, this visit should be completed on Day 28 (± 2 days) of Cycle 4.  For subjects who complete dosing after Cycle 4, EOT Visit should be completed within 28 days after the 
last day of the previous cycle. 
c Safety Follow-up Visit is performed 28 days (± 3 days) after the last dose of CC-90009 for all subjects. May be performed by telephone contact if pregnancy testing is not 
required (refer to footnote “i”). 
d Supplements to be administered for at least 3 days after the last dose in each cycle. Supplementation may be prolonged if hypocalcemia occurs (refer to Section 7.2.13.2). 
Subjects to start supplements at least 3 days prior to Day 1 of Cycles 3 and 4 as per Section 7.2.
e Subjects will be closely monitored during the administration of CC-90009 and for at least 1 hour after. Subjects should be adequately hydrated to prevent potential tumor lysis 
syndrome (TLS) (eg, 2 to 3 liters of oral or IV fluids per day) starting the day prior to CC-90009 administration and continuing through each day of CC-90009 
administration. Refer to Section 7.2.12 for information on dose interruptions. The SRC may decide to evaluate alternate dosing schedules (eg, increasing from 5 to up to 
10 consecutive days of CC-90009 administration) based on their review of available clinical and laboratory safety data, PK profiles, and PD findings. Subjects should be 
administered Cycle ≥ 2 of CC-90009 in a Limited Stay Unit (LSU) or as in patient. Subjects experiencing Grade ≥ 2 hypocalcemia during any cycle should be administered 
CC-90009 in the inpatient setting for subsequent cycles (an exception can be made for subjects with grade 2 hypocalcemia lasting less than 24 hours that recovers without IV 
calcium [eg, calcium gluconate or calcium chloride] after discussion with the Celgene medical monitor).
f Multiple measurements performed on this day. 
g Triplicate ECGs will be performed on Day 1 of each cycle (refer to Section 6.2.5) and a single ECG obtained at the EOT visit. 
h The EOT Visit LVEF is not required if the prior LVEF was performed within 56 days. 
I Per the PPP, a pregnancy test is required 28 days after the last dose of for all FCBP. For FCBP with irregular menstrual periods, a pregnancy test is required every 14 days (ie, 
Day 15 of Cycles ≥ 2 and at 14 and 28 days after the last dose of CC-90009).
j
In the event of Grade ≥ 2 hypocalcemia or symptoms of hypocalcemia (eg, carpopedal spasm, tetany, seizures, etc), subjects must be hospitalized. Also, if Grade ≥ 2 
hypocalcemia and abnormal levels of serum albumin occurs, a serum ionized calcium test must be performed. Refer to Section 7.2.13.2 for hypocalcemia management 
guidelines. Refer to Section 6.2.8 for required days and timing of tests. Subjects who experienced Grade ≥ 2 hypocalcemia during Cycle 1, require testing Days 1-7 at 6 and 
12 hours postdose. All other subjects require testing prior to dosing. If intra-subject dose escalation occurs, subjects should be treated as in Cycle 1.
k If intra-subject dose escalation occurs, blood samples for PD assays will be collected during the first cycle only at the increased dose; see laboratory manual for details. Multiple 
blood samples will be collected for this assay on the specified Days 1, 2, 3. Refer to Section 6.6. 
l
Bone marrow samples for biomarker PD assessment are mandatory. When applicable (refer to time points in the table above), bone marrow samples for biomarker PD 
assessment will be obtained at the same time as a scheduled efficacy assessment. If sufficient bone marrow aspirate specimen is not available, peripheral blood may be 
submitted in place of the BMA specimen for biomarker studies (eg, MRD); see laboratory manual for details.
m If end of Cycle 2 (Day 28 ± 3 days) samples are obtained on Day 1 of Cycle 3, they must be obtained prior to CC-90009 administration. Additionally, bone marrow aspirates 
and biopsies may be obtained in both Part A and Part B, after a CR is confirmed, if relapse is suspected, or following treatment discontinuation to elucidate effects of long-
term treatment or resistance mechanisms. Additional aspirates and biopsies will be collected as clinically indicated based on the Investigator’s medical assessment.
n For subjects that complete dosing in Cycle 4, performed/obtained once on Day 28 (± 3 days). For subjects that continue (after consultation with Medical Monitor) beyond 
Cycle 4, efficacy and bone marrow PD assessments may be obtained to confirm a CR, if relapse is suspected, or following treatment discontinuation to elucidate effects of 
long-term treatment or resistance mechanisms. Additional aspirates and biopsies will be collected as clinically indicated based on the Investigator’s medical assessment. Refer 
to Section 6.3.2 and Section 6.4.
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o
Blood samples for PK are to be collected in Cycle 2 only; on Day 7 there is a pre-dose and 24 hour postdose sample Section 6.5.1.
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Appendix P:
The Operating Characteristics of the Proposed Bayesian Safety 
Monitoring Plan
The enrollment may stop to ensure the posterior probability of excess AE rate exceeding 25% is 
not more than 70%, ie, when:

Prob (rate of AEs that fulfill DLT criteria or treatment related AEs leading to dose reduction 
or discontinuation or rate of sepsis >0.25|data, a, b) > 0.70.
Where a, b are parameters of Beta distribution. Weakly informative priors, ie, beta (0.5, 0.5), 
may be used for the posterior probability calculations.  The excess toxicity of 25% is established 
based on the inputs from clinical with threshold of 70% based on empirical data analysis.
Table 39 below shows the simulation results of the probability to stop further enrollment based 
on above condition with various true toxicity rate.
Table 39:
The Operating Characteristics for Bayesian Monitor Plan
The True Toxicity Rate
Number of 
Subjects
Number Of 
Subjects with AEs 
That Fulfill DLT 
Criteria or 
Treatment 
Related AEs 
Leading to 
Treatment 
Reduction or 
Discontinuation 
or AEs of Sepsis 
for Stop
0.1
0.15
0.2
0.25
0.3
0.35
0.4
0.45
8
3
3.8%
10.5%
20.3%
32.2%
44.8%
57.2%
68.5%
78.0%
10
4
5.3%
14.1%
26.2%
39.9%
53.7%
66.3%
76.8%
85.1%
13
5
5.8%
15.8%
29.6%
45.0%
59.9%
72.8%
82.9%
90.1%
17
6
6.2%
17.3%
33.0%
50.4%
66.5%
79.5%
88.7%
94.4%
21
7
6.4%
18.3%
35.6%
54.5%
71.5%
84.2%
92.3%
96.8%
24
8
6.4%
18.7%
36.6%
56.3%
73.6%
86.1%
93.7%
97.6%
28
9
6.5%
19.1%
37.8%
58.5%
76.4%
88.6%
95.4%
98.5%
32
10
6.5%
19.4%
38.9%
60.6%
78.8%
90.6%
96.6%
99.0%
35
11
6.5%
19.5%
39.4%
61.5%
79.9%
91.5%
97.2%
99.3%
39
12
6.5%
19.6%
40.0%
62.9%
81.5%
92.8%
97.8%
99.5%
Note: Only unique stopping boundaries are presented up to the estimated maximum enrollment of 40 subjects in an 
expansion cohort.
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Final: 31 Mar 2022
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Appendix Q:
Blood Collection for PK Analysis
Table 40:
Blood Pharmacokinetic Sampling Schedule for Cycle 1 in Part A 
for D1-5 and Alternative Schedules with up to 10 consecutive dosing 
days (eg, D1-7 and D1-10)
Time Relative to CC-90009 
Administration
Collection Window
Day 1
Day 3
Day 4
Cycle 1 
Last 
Dosea
0
≤ 30 minutes prior to start
X
X
X
X
Mid-infusion (eg, at 15 
minutes in a 30 minute 
infusion)b
± 1 minute
X
X
15 minutes after EOI
± 5 minutes
X
X
30 minutes after EOI
± 5 minutes
X
X
1 hour after EOI
± 5 minutes
X
X
X
2 hours after EOI
± 10 minutes
X
X
4 hours after EOI
± 10 minutes
X
X
X
8 hours after EOI
± 30 minutes
X
X
12 hours after EOI
± 2 hours
X
24 hours after EOI
± 3 hours
Xc
X
EOI = end of infusion/injection.
a Day of last dose in a schedule with up to 10 consecutive days of CC-90009 dosing. On the D1-5 schedule, PK will be collected 
on Cycle 1 Day 5. On the D1-7 schedule, PK will be collected on Cycle 1 Day 7. On the D1-10 schedule, PK will be collected 
on Cycle 1 Day 10. If a dosing schedule with less than 5 days is tested, the intensive PK samples for the last dosing day will not 
be collected.
b In cases where the only access for drug administration is the central line, mid-infusion PK draws may be omitted.
c 24 hours after EOI on Day 1 occurs on Day 2. Must be drawn prior to the administration of CC-90009 on Day 2.
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Table 41:
Blood Pharmacokinetic Sampling Schedule for Cycle 2 in Part A 
for D1-5 and Alternative Schedules with up to 10 consecutive dosing 
days (eg, D1-7 and D1-10)
Time Relative to 
CC-90009 
Administration
Collection Window
Day 1
Day 2
Day 3
Day 4
Cycle 
2 Last 
Dosea
0
≤ 30 minutes prior to start
X
X
X
X
Mid-infusion (eg, at 15 
minutes in a 30 minute 
infusion)b
± 1 minutes
X
X
24 hours after EOI
± 3 hours
X
EOI = end of infusion/injection.
a Day of last dose in a schedule with up to 10 consecutive days of CC-90009 dosing. If it’s a D1-5 schedule, PK will be collected 
on Cycle 2 Day 5. If it’s a D1-7 schedule, PK will be collected on Cycle 2 Day 7. If it’s a D1-10 schedule, PK will be collected
on Cycle 2 Day 10. If dosing is not scheduled for Cycle 2 last dosing day, last dosing day PK will not be collected. 
b In cases where the only access for drug administration is the central line, mid-infusion PK draws may be omitted.
Table 42:
Blood Pharmacokinetic Sampling Schedule for Cycle 1 in Part A 
for D1-3/D8-10 Schedule
Time Relative to CC-90009 
Administration
Collection Window
Day 1
Day 3
Day 8
Day 10
0
≤ 30 minutes prior to start
X
X
X
X
Mid-infusion (eg, at 15 minutes 
in a 30 minute infusion)a
± 1 minute
X
X
15 minutes after EOI
± 5 minutes
X
X
30 minutes after EOI
± 5 minutes
X
X
1 hour after EOI
± 5 minutes
X
X
X
2 hours after EOI
± 10 minutes
X
X
4 hours after EOI
± 10 minutes
X
X
X
8 hours after EOI
± 30 minutes
X
X
12 hours after EOI
± 2 hours
X
24 hours after EOI
± 3 hours
Xb
Xb
Xb
Xb
EOI = end of infusion/injection.
a In cases where the only access for drug administration is the central line, mid-infusion PK draws may be omitted.
b 24 hours after EOI on day 1 occurs on Day 2; 24 hours after Day 3 occurs on Day 4; 24 hours after Day 8 occurs on Day 9; 24 
hours after Day 10 occurs on Day 11. Must be drawn prior to the administration of CC-90009 on Day 2 and Day 9.
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193
Table 43:
Blood Pharmacokinetic Sampling Schedule for Cycle 2 in Part A 
for D1-3/D8-10 Schedule
Time Relative to CC-90009 
Administration
Collection Window
Day 1
Day 3
Day 8
Day 10
0
≤ 30 minutes prior to start
X
X
Mid-infusion (eg, at 15 
minutes in a 30 minute 
infusion)a
± 1 minutes
X
X
X
24 hours after EOI
± 3 hours
Xb
Xb
Xb
Xb
EOI = end of infusion/injection.
a In cases where the only access for drug administration is the central line, mid-infusion PK draws may be omitted.
b 24 hours after EOI on day 1 occurs on Day 2; 24 hours after Day 3 occurs on Day 4; 24 hours after Day 8 occurs on Day 9; 24 
hours after Day 10 occurs on Day 11. Must be drawn prior to the administration of CC-90009 on Day 2 and Day 9.
Table 44:
Blood Pharmacokinetic Sampling Schedule in Part B: 3.6 mg Day 1-
5 Schedule
Time Relative to CC-90009 
Administration
Collection Window
Intensive
Sparse
Cycle 1 Day 1
0
≤ 30 minutes prior to start
X
Mid-infusion (eg, at 15 minutes in a 
30 minute infusion)a
± 1 minute
X
15 minutes after EOI
± 5 minutes
X
30 minutes after EOI
± 5 minutes
X
X
1 hour after EOI
± 5 minutes
X
X
2 hours after EOI
± 10 minutes
X
4 hours after EOI
± 10 minutes
X
X
8 hours after EOI
± 30 minutes
X
12 hours after EOI
± 2 hours
X
24 hours after EOI
± 3 hours
Xb
Xb
Cycles 2-4
Second to last dosing day, pre-dose
≤ 30 minutes prior to start
X
X
Last dosing day, pre-dose
≤ 30 minutes prior to start
X
X
EOI = end of infusion/injection. 
a In cases where the only access for drug administration is the central line, mid-infusion PK draws may be omitted.
b 24 hours after EOI on day 1 occurs on Day 2. Must be drawn prior to the administration of CC-90009 on Day 2.
1.0
Approved
930183898
14.0
v