Randomized Phase 2 Study of Daunorubicin and Cytarabine Liposome + Pomalidomide Versus Daunorubicin and Cytarabine Liposome in Newly Diagnosed AML With MDS-Related Changes
Phase: PHASE2
Conditions: Acute Myeloid Leukemia, Acute Myeloid Leukemia Post Cytotoxic Therapy, Acute Myeloid Leukemia With Multilineage Dysplasia, Chronic Myelomonocytic Leukemia, Myelodysplastic Syndrome, Myeloproliferative Neoplasm
Sponsor: National Cancer Institute (NCI)

NCI Protocol #:  10434 
Version Date:  March 3, 2025 
i 
 
NCI Protocol #:  10434 
Local Protocol #:  TBD 
Protocol Version Date: March 3, 2025 
 
Protocol Title:  Randomized Phase 2 Study of daunorubicin and cytarabine liposome + 
Pomalidomide versus daunorubicin and cytarabine liposome in Newly Diagnosed AML with 
MDS-Related Changes. 
 
Protocol Version Date: March 3, 2025 
 
The summary of changes table below provides a detailed summary and rationale for all changes to 
protocol #10434, from amendment 11 (Version 7/11/2023) to amendment 12 (Version 3/3/2025). 
Although this study is now closed for accrual, the amendment is being submitted to provide details 
of the change of Dr. Luznik laboratory.  
 
SUMMARY OF CHANGES-PROTOCOL 
Summary of changes for Amendment #12 version March 3, 2025 
# 
Section 
Comment 
1 
5.1 
Updated the Table footnote to specify the location of Dr. Luznik 
laboratory 
2 
5.3.2.1 
Revised the sub-section header to Scheduling of Specimen Collections 
from UNC to the Luznik Laboratory at JHU (only applicable to UNC, no 
other sites will ship samples to the Luznik Laboratory). 
3 
5.6.1 
Revised the sub-section header to: Shipping of Specimens to the Luznik 
Laboratory at JHU. 
4 
5.7 
Updated lab/lab PI/lab PI email information for Dr. Luznik’s new lab 
5 
5.8.2 
Revised this section to include updated information for Dr. Luznik 
6 
5.9.1 
Revised this section to include updated information for Dr. Luznik 
7 
11 
Updated footnotes to Luznik Laboratory at JHU.  
 
 

NCI Protocol #:  10434 
Version Date:  March 3, 2025 
2 
 
NCI Protocol #: 
10434 
 
Local Protocol #: 
TBD 
 
ClinicalTrials.gov Identifier:  TBD 
 
TITLE:  Randomized Phase 2 Study of daunorubicin and cytarabine liposome + Pomalidomide 
versus daunorubicin and cytarabine liposome in Newly Diagnosed AML with MDS-Related 
Changes 
 
 
Corresponding Organization: LAO-OH007 / Ohio State University Comprehensive Cancer 
Center LAO 
 
Principal Investigator: 
Joshua F. Zeidner, MD 
University of North Carolina 
Lineberger Comprehensive Cancer Center 
Houpt Building, 3rd floor, Room 3138 
170 Manning Drive, CB#7305 
Chapel Hill, NC 27599-7305 
Telephone:  (919) 962-5164 
Fax:  (919) 966-6735 
Joshua_Zeidner@med.unc.edu 
 
Translational PI: 
Leo Luznik, MD 
Baylor College of Medicine  
1 Baylor Place  
Houston, TX 77030 
Leonido.luznik@bcm.edu 
Participating Organizations  
LAO-11030 / University Health Network Princess Margaret Cancer Center LAO 
LAO-CA043 / City of Hope Comprehensive Cancer Center LAO 
LAO-CT018 / Yale University Cancer Center LAO 
LAO-MA036 / Dana-Farber - Harvard Cancer Center LAO 
LAO-MD017 / JHU Sidney Kimmel Comprehensive Cancer Center LAO 
LAO-OH007 / Ohio State University Comprehensive Cancer Center LAO 
LAO-PA015 / UPMC Hillman Cancer Center LAO 
LAO-TX035 / University of Texas MD Anderson Cancer Center LAO 
LAO-NCI / National Cancer Institute LAO 
 
Statistician:  
 
 
Study Coordinator: 
Anastasia Ivanova, PhD  
 
Erica Moore 
UNC Gillings School of Global Public Health 
 
450 West Drive 

NCI Protocol #:  10434 
Version Date:  March 3, 2025 
3 
 
3103-C McGavran-Greenberg Hall, CB #7420  
Chapel Hill, NC 27599 
Chapel Hill, NC 27599 
 
Telephone:  +1 (984) 974-8655 
Telephone:  (919) 843-8086  
ermulous@email.unc.edu 
aivanova@bios.unc.edu 
 
Responsible Research Coordinator:  
 
Responsible Data Manager:  
Erica Moore 
 
Mykal Lynch 
450 West Drive 
 
450 West Drive 
Chapel Hill, NC 27599 
 
 
 
 
 
Chapel Hill, NC 27599 
Telephone:  +1 (984) 974-8655  
 
 
 
 
Telephone:  +1 (919) 692-8552 
ermulous@email.unc.edu 
 
 
 
 
 
vanessa lynch@med.unc.edu 
 
 
NCI-Supplied Agent:  Pomalidomide (CC-4047) (NSC 767909) 
Other Agent:  daunorubicin and cytarabine liposome (NSC 775341), Commercial; Cytarabine 
(NSC 63878), Commercial 
 
IND #:  
 
IND Sponsor:  DCTD, NCI 
 
 
Protocol Type / Version # / Version Date: 
Original / December 11, 2020 
 
 
 
 
Revision 1 / February 10, 2021 
 
 
 
 
Revision 2a / April 20, 2021 
 
 
 
 
Revision 2b / June 15, 2021 
 
 
 
 
Revision 3 / October 15, 2021 
 
 
 
 
Revision 4/ November 8, 2021 
                                                                              Revision 5/ January 23, 2022 
                                                                              Revision 6/ April 14, 2022 
 
 
 
 
Revision 7/June 27, 2022 
 
 
 
 
Revision 8/ August 1, 2022 
 
 
 
 
Revision 9/ September 20, 2022 
 
 
 
 
Revision 10/ October 5, 2022 
 
 
 
 
Revision 11/ November 7, 2022 
 
 
 
 
Revision 12/ January 11, 2023 
 
 
 
 
Revision 13/July 11, 2023 
 
 
 
 
Revision 14/March 3, 2025 
 
 
 

NCI Protocol #:  10434 
Version Date:  March 3, 2025 
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TABLE OF CONTENTS 
SCHEMA ........................................................................................................................................4 
1. 
OBJECTIVES ....................................................................................................................9 
1.1 
Primary Objective ....................................................................................................9 
1.2 
Secondary Objectives ...............................................................................................9 
1.3 
Exploratory Objectives ..........................................................................................10 
2. 
BACKGROUND ..............................................................................................................10 
2.1 
Study Disease(s).....................................................................................................10 
2.2 
CTEP IND Agent ...................................................................................................11 
2.3 
Other Agent ............................................................................................................19 
2.4 
Rationale ................................................................................................................20 
2.5 
Correlative Studies Background ............................................................................24 
3. 
PATIENT SELECTION .................................................................................................27 
3.1 
Eligibility Criteria ..................................................................................................27 
3.2 
Exclusion Criteria ..................................................................................................29 
3.3 
Inclusion of Women and Minorities ......................................................................30 
4. 
REGISTRATION PROCEDURES ................................................................................31 
4.1 
Investigator and Research Associate Registration with CTEP ..............................31 
4.2 
Site Registration .....................................................................................................33 
4.3 
Patient Registration ................................................................................................35 
4.4 
General Guidelines .................................................................................................37 
5. 
BIOMARKER, CORRELATIVE, AND SPECIAL STUDIES ...................................38 
5.1 
Summary Table for Specimen Collection ..............................................................38 
5.2 
Summary Table(s) for Interventional Radiologist for Research Biopsies .............39 
5.3 
Specimen Procurement Kits and Scheduling .........................................................39 
5.4 
Specimen Tracking System Instructions ................................................................40 
5.5 
Specimen Collection ..............................................................................................44 
5.6 
Shipping of Specimens from Clinical Site to Other Laboratories .........................45 
5.7 
Biomarker Plan ......................................................................................................49 
5.8 
Integrated Correlative Studies ................................................................................53 
5.9 
Exploratory/Ancillary Correlative Studies ............................................................54 
6. 
TREATMENT PLAN ......................................................................................................55 
6.1 
Agent Administration .............................................................................................55 
6.2 
Safety Run-in .........................................................................................................56 
6.3 
Dose Escalation 3 + 3 Design ................................................................................56 
6.4 
Definition of a Dose Limiting Toxicity .................................................................56 
6.5 
Randomization Phase .............................................................................................57 
6.6 
General Concomitant Medication and Supportive Care Guidelines ......................60 
6.7 
Duration of Therapy ...............................................................................................62 
6.8 
Duration of Follow-Up ..........................................................................................63 

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7. 
DOSING DELAYS/DOSE MODIFICATIONS ............................................................64 
7.1 
Pomalidomide ........................................................................................................64 
7.2 
Daunorubicin and cytarabine liposome .................................................................65 
8. 
PHARMACEUTICAL INFORMATION ......................................................................66 
8.1 
CTEP IND Agent(s) ...............................................................................................66 
8.2 
Commercial Agent .................................................................................................70 
9. 
STATISTICAL CONSIDERATIONS ...........................................................................72 
9.1 
Study Design/Endpoints.........................................................................................72 
9.2 
Sample Size/Accrual Rate ......................................................................................74 
9.3 
Stratification Factors ..............................................................................................75 
9.4 
Analysis of Secondary Endpoints ..........................................................................75 
9.5 
Reporting and Exclusions ......................................................................................75 
9.6 
Data Safety Monitoring Board ...............................................................................76 
10. 
ADVERSE EVENTS:  LIST AND REPORTING REQUIREMENTS ......................76 
10.1 
Comprehensive Adverse Events and Potential Risks List (CAEPR) .....................76 
10.2 
Adverse Event Characteristics ...............................................................................82 
10.3 
Expedited Adverse Event Reporting ......................................................................83 
10.4 
Routine Adverse Event Reporting .........................................................................87 
10.5 
Pregnancy ...............................................................................................................87 
10.6 
Secondary Malignancy ...........................................................................................88 
10.7 
Second Malignancy ................................................................................................89 
11. 
STUDY CALENDAR ......................................................................................................90 
11.1 
Time and Events Table:  Induction ........................................................................90 
11.2 
Time and Events Table:  Reinduction ....................................................................93 
11.3 
Time and Events for Consolidation .......................................................................97 
12. 
MEASUREMENT OF EFFECT ....................................................................................99 
12.1 
Antitumor Effect – Hematologic Tumors ..............................................................99 
13. 
STUDY OVERSIGHT AND DATA REPORTING / REGULATORY 
REQUIREMENTS ...........................................................................................................99 
13.1 
Study Oversight .....................................................................................................99 
13.2 
Data Reporting .......................................................................................................99 
13.3 
Data Quality Portal ..............................................................................................102 
13.4 
Collaborative Agreements Language ...................................................................102 
13.5 
Incidental/Secondary Findings Disclosure Procedure .........................................104 
14. 
REFERENCES ...............................................................................................................105 
APPENDIX A 
PERFORMANCE STATUS CRITERIA ............................................109 
APPENDIX B 
FORMULA TO ESTIMATE RENAL FUNCTION USING SERUM 
CREATININE ................................................................................................................110 

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APPENDIX C 
PATIENT CLINICAL TRIAL WALLET CARD ..............................111 
APPENDIX D 
POMALIDOMIDE RISKS OF FETAL EXPOSURE, PREGNANCY 
TESTING GUIDELINES AND ACCEPTABLE BIRTH CONTROL METHODS
 
112 
APPENDIX E 
POMALIDOMIDE EDUCATION AND COUNSELING GUIDANCE 
DOCUMENT 118 
APPENDIX F 
POMALIDOMIDE INFORMATION SHEET ...................................123 
APPENDIX G 
CELGENE PREGNANCY PREVENTION AND COUNSELING 
PROGRAM SITE COUNSELOR IDENTIFICATION FORM ...............................126 
APPENDIX H 
PATIENT’S MEDICATION DIARY FOR POMALIDOMIDE ......127 
APPENDIX I 
CYTARABINE DRUG INFORMATION FOR HIGH DOSE 
CYTARABINE (HiDAC) CONSOLIDATION ...........................................................129 
APPENDIX J 
RESPONSE CRITERIA FOR AML ....................................................131 
APPENDIX K 
Requisition Form: Molecular Genetics Laboratory, UNC Hospitals
 
132 
APPENDIX L 
Tumor ProcurEment Facility speciment shipping instructions ........134 
APPENDIX M 
Cryopreservation of PBMC’s from Fresh PB and BM Samples .......136 
 
 
 

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1. 
OBJECTIVES 
 
1.1 
Primary Objective 
 
1.1.1 To establish recommended phase 2 dose (RP2D) of Pomalidomide after daunorubicin and 
cytarabine liposome induction. 
 
1.1.2 To compare the rate of overall complete response (CR)/complete response with 
incomplete hematologic recovery (CRi) with daunorubicin and cytarabine liposome + 
pomalidomide versus daunorubicin and cytarabine liposome alone in newly diagnosed 
Acute Myeloid Leukemia (AML) with preexisting myelodysplastic syndrome (MDS), 
chronic myelomonocytic leukemia (CMML), or myeloproliferative neoplasm (MPN); 
therapy-related AML (t-AML); or AML with myelodysplasia-related changes (MRC) 
based on cytogenetics or morphologic dysplasia. 
 
1.2 
Secondary Objectives 
 
1.2.1 To evaluate and compare rates of CR (full hematologic recovery) between daunorubicin 
and cytarabine liposome + pomalidomide versus daunorubicin and cytarabine liposome 
alone in newly diagnosed AML with preexisting MDS, CMML or MPN, t-AML or 
AML with MRC 
 
1.2.2 To evaluate and compare toxicities (including treatment-related mortality) of 
daunorubicin and cytarabine liposome + pomalidomide versus daunorubicin and 
cytarabine liposome alone in newly diagnosed AML with preexisting MDS, CMML or 
MPN, t-AML, or AML with MRC based on cytogenetics or morphologic dysplasia.  
 
1.2.3 To detect and compare the presence of minimal residual disease (MRD) by flow 
cytometry in those who achieve CR/CRi with daunorubicin and cytarabine liposome + 
pomalidomide versus daunorubicin and cytarabine liposome alone in newly diagnosed 
AML with preexisting MDS, CMML or MPN, t-AML, or AML with MRC based on 
cytogenetics or morphologic dysplasia.  
 
1.2.4 To compare median event-free survival (EFS) of daunorubicin and cytarabine liposome 
+ pomalidomide versus daunorubicin and cytarabine liposome alone in newly diagnosed 
AML with preexisting MDS, CMML or MPN, t-AML, or AML with MRC based on 
cytogenetics or morphologic dysplasia.  
 
1.2.5 To compare median overall survival (OS) of daunorubicin and cytarabine liposome + 
pomalidomide versus daunorubicin and cytarabine liposome alone in newly diagnosed 
AML with preexisting MDS, CMML or MPN, t-AML, or AML with MRC based on 
cytogenetics or morphologic dysplasia.  
 
1.2.6 To compare median and 2-year disease-free survival (DFS) after CR/CRi with 
daunorubicin and cytarabine liposome + pomalidomide versus daunorubicin and 
cytarabine liposome alone in newly diagnosed AML with preexisting MDS, CMML or 

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MPN, t-AML, or AML with MRC based on cytogenetics or morphologic dysplasia.  
 
1.2.7 To compare rates of allogeneic stem cell transplant (SCT) after daunorubicin and 
cytarabine liposome + pomalidomide versus daunorubicin and cytarabine liposome 
alone in newly diagnosed AML with preexisting MDS, CMML or MPN, t-AML, or 
AML with MRC based on cytogenetics or morphologic dysplasia. 
 
1.3 
Exploratory Objectives 
 
1.3.1 To assess for molecular biomarkers, Aiolos expression, and immune correlates of 
response with daunorubicin and cytarabine liposome + pomalidomide versus 
daunorubicin and cytarabine liposome alone in newly diagnosed AML with preexisting 
MDS, CMML or MPN, t-AML, or AML with MRC based on cytogenetics or 
morphologic dysplasia. 
 
1.3.2 To assess for differences in MRD by molecular based platforms in daunorubicin and 
cytarabine liposome + pomalidomide versus daunorubicin and cytarabine liposome alone 
in newly diagnosed AML with preexisting MDS, CMML or MPN, t-AML, or AML with 
MRC based on cytogenetics or morphologic dysplasia. 
 
2. 
BACKGROUND 
 
2.1 
Study Disease(s) 
 
Acute Myeloid Leukemia (AML) patients have a poor prognosis with conventional 
chemotherapy agents.  The prognosis and long-term outcomes of AML have been shown to be 
independently associated with cytogenetics and more recently molecular genomics.  The 
European Leukemia Net (ELN) initially proposed stratification of patients to four different risk 
groups (favorable, intermediate-1, intermediate-2, and adverse) based on diagnostic cytogenetics 
and molecular mutations [1].  The ELN updated their proposed risk stratification in 2017 based 
on prognostic mutational status to reflect three different risk groups (favorable, intermediate and 
adverse)[2, 3].  Mrozek et al. retrospectively analyzed outcomes of 1,550 adult AML patients 
treated on Cancer and Leukemia Group B clinical trials from 1985-2006 based on ELN risk 
group and age (<60 and ≥60 years) [4].  There was a significant difference in outcomes (i.e. CR, 
OS, and DFS) between favorable, intermediate (including intermediate-1 and -2), and adverse-
risk groups among both younger and older patients.  Younger AML patients (<60 years) with 
adverse-risk were shown to have a CR rate of approximately 50% with induction chemotherapy, 
median OS and DFS=0.8 and 0.6 years, respectively; whereas older AML patients (≥60 years) 
with adverse-risk had dismal outcomes (39% CR rate, median OS and DFS=0.5 years).  Thus, 
outcomes are extremely poor in patients with newly diagnosed adverse-risk AML.  
 
Genomic risk assessment is typically performed as a panel in newly diagnosed AML patients and 
can take 1-2 weeks before final results are available.  Fluorescence in situ hybridization (FISH) 
and cytogenetics can be more rapidly ascertained within 48-72 hours.  The majority of newly 
diagnosed AML patients are treated with induction therapy prior to the results of their full 
genomic analyses with the exception of fms-like tyrosine kinase 3 (FLT3) mutations, which are 

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now available as a rapid assay to determine whether patients may benefit from the addition of 
Midostaurin, a FLT3 inhibitor, in newly diagnosed AML patients with FLT3 mutations.  
 
Induction chemotherapy with infused cytarabine plus an anthracycline (‘7+3’) has been widely 
used as the standard of care for younger, fit AML patients despite suboptimal outcomes.  
However, outcomes are extremely poor in patients with secondary AML and/or adverse-risk 
cytogenetics.  A randomized phase 3 trial comparing amonafide + cytarabine versus 7+3 
induction in newly diagnosed secondary AML patients found no difference in response between 
either arm (CR rate=46% versus 45%, respectively) and dismal OS outcomes (median OS=7 
months on both arms) [5].  A randomized phase 3 study compared daunorubicin and cytarabine 
liposome versus 7+3 in newly diagnosed AML patients 60-75 years with MRC.  AML with 
MRC includes patients with secondary AML (i.e. therapy-related AML or AML from preexisting 
MDS/CMML) and those with MDS-related cytogenetics according to the World Health 
Organization (WHO) [6].  A total of 309 patients were randomized to receive daunorubicin and 
cytarabine liposome or 7+3.  Daunorubicin and cytarabine liposome led to a significantly higher 
CR rate (47.7% versus 33.3%), median EFS (2.5 versus 1.3 months), and OS (9.6 versus 6.0 
months) when compared with 7+3.  Nonetheless, these findings highlight the dismal overall 
outcomes in this patient population despite the improvement seen with daunorubicin and 
cytarabine liposome.  Based on these findings, daunorubicin and cytarabine liposome was Food 
and Drug Administration (FDA)-approved for the treatment of newly diagnosed therapy-related 
AML or AML with MRC, and represents a new standard of care for this patient population [7].  
Optimal frontline management of AML with MRC represents an unmet need and novel therapies 
are urgently needed to improve clinical outcomes. 
 
2.2 
CTEP IND Agent 
 
2.2.1 Pomalidomide (CC-4047) (NSC 767909) 
 
Pomalidomide (CC-4047) is a member of a class of pharmaceutical compounds known as 
immunomodulatory drugs (IMiDs) that was approved on February 8, 2013 by the United States 
(U.S.) Food and Drug Administration (FDA) for the treatment of patients with multiple myeloma 
(MM) who have received at least two prior therapies, including lenalidomide and bortezomib, 
and have demonstrated disease progression on or within 60 days of completion of the last 
therapy [8].  Other IMiD compounds include thalidomide and lenalidomide, which are approved 
for use in treatment of MM and myelodysplastic syndromes (MDS) and are under investigation 
for a number of other hematologic neoplasms.  Pomalidomide shares a number of the beneficial 
pharmacologic properties of thalidomide and lenalidomide, but it is a more potent anti-
proliferative immunomodulating agent than either drug.  The pharmacodynamic properties of 
pomalidomide are of potential therapeutic benefit in the treatment of various hematologic 
neoplasms (MM, myelofibrosis with myeloid metaplasia [MMM]). 
 
2.2.1.1 
Mechanism of Action 
 
IMiD compounds may affect the immune system in several ways, such as inducing immune 
responses, enhancing activity of immune cells, altering and modulating the induction of pro- and 
anti-inflammatory cytokines, and inhibiting inflammation [8].  IMiD compounds are also 

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antiangiogenic.  Although their precise mechanism of action is currently under investigation, 
these agents offer promise for their anti-cancer and anti-inflammatory activities. 
 
Pomalidomide has a dual mechanism of action; it is directly tumoricidal for MM cells, and it also 
has immunomodulatory activity with direct effects on T cell and natural killer (NK) cell-
mediated immunity [8].  Pomalidomide’s pleiotropic activities in a range of cell types including 
MM cells and immune effector cells suggests the existence of multiple molecular target 
molecules and downstream modulation of multiple molecular pathways.  The possibility exists 
that a common molecular mediator present in various cell types that is proximal to the 
downstream modulation of multiple signaling pathways is involved in the inhibition of 
proliferation and induction of apoptosis in tumor cells and in the activation of immune effector 
cells.  Cereblon (CRBN), a substrate receptor for the E3 ubiquitin ligase complex, is required for 
the teratogenic effects of thalidomide in zebrafish and chicken embryos; forms a ubiquitin E3 
ligase complex with DNA damage-binding protein 1 (DDB1), cullin 4 (CUL4), and protein 
Roc1; and thalidomide treatment has been shown to inhibit the ubiquitin ligase activity of the 
complex [9].  Pomalidomide and lenalidomide are more potent structural analogs of thalidomide 
and it was demonstrated that both pomalidomide and lenalidomide interact with human cereblon 
[8].  Upon engagement with cereblon, the thalidomide analogs lenalidomide and pomalidomide 
induce ubiquitination and proteasomal degradation of two key transcription factors Ikaros 
(encoded by the gene IKZF1) and Aiolos (encoded by the gene IKZF3) that regulate immune cell 
development and homeostasis [10].  Pomalidomide and lenalidomide bind human cereblon and 
the expression of CRBN in myeloma cells is linked to both the efficacy of pomalidomide and 
lenalidomide and to the acquisition of resistance to lenalidomide [11].  In activated human T 
cells in which CRBN was transiently decreased, IL-2 and TNF-α induction by pomalidomide 
was markedly reduced.  Since IL-2 and TNF-α are important for tumor surveillance by activated 
T cells, these results indicate that some of the immunomodulatory effects of pomalidomide are 
mediated via initial binding to CRBN. 
 
An important aspect of the clinical use of lenalidomide is that tumors can acquire resistance to 
lenalidomide over time [12-14].  In vitro studies of long-term exposure to increasing 
concentrations of lenalidomide until the cells were resistant to its anti-proliferative effects 
indicated that CRBN expression decreased concurrently with the decrease in efficacy of 
lenalidomide [14].  However, pomalidomide maintained efficacy, although somewhat lower 
potency, in these lenalidomide resistant cells.  It is not clear why pomalidomide was still 
efficacious in cells in which the concentration of CRBN was relatively decreased.  It is possible 
that these molecules interact differentially with other proteins or induce a different 
conformational change in CRBN, resulting in differential effects within the context of the E3 
ligase complex [11].  In a MM cell line made resistant to lenalidomide and pomalidomide, 
CRBN was undetectable, supporting the conclusion that CRBN is essential for the activity of 
these immunomodulatory compounds. 
 
2.2.1.2 
Non-Clinical Studies  
 
The pleiotropic activities of pomalidomide on a range of cell types including MM cells and 
immune effector cells suggest modulation of multiple molecular pathways [8].  Indeed, activity 
of pomalidomide and lenalidomide are cell type- and context-dependent [15-20];;.  Activities 

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include effects on the cell cycle such as G0/G1 arrest associated with the upregulation of the 
cyclin dependent kinase (CDK) inhibitor p21WAF-1 [19], downregulation of the expression of 
interferon regulatory factor 4 (IRF4) in MM cell lines,[21], and modulation of Rho guanosine-5'-
triphosphate binding and hydrolyzing enzymes (GTPases) which are critical for actin 
hyperpolymerization and immune synapse formation [20]. 
 
 
Pomalidomide has potent anti-inflammatory activity in vitro [8].  Specifically, in 
lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC), the 
pomalidomide tumor necrosis factor-α (TNF-α) 50% inhibitory concentration (IC50) is ~13 nM 
[22].  Pomalidomide also inhibits LPS-induced PBMC production of the pro-inflammatory 
cytokines and chemokines interleukin (IL)-1β, IL-6, IL-12, monocytes chemoattractant protein 
(MCP-1), macrophage inflammatory protein (MIP)-1α and elevates production of the anti-
inflammatory cytokine IL-10.  Pomalidomide augments T helper cell type 1 (Th1) (cell-
mediated) and inhibits T helper cell type 2 (Th2) (humoral-mediated) T cell responses [8].  
Pomalidomide enhances T cell proliferation and production of the Th1 cytokines IL-2 and 
interferon gamma (IFN-γ) by freshly isolated human peripheral T cells in vitro [23].  Moreover, 
the addition of pomalidomide to naive splenocytes stimulated in vitro with immobilized anti-
CD3 antibody enhanced the production of IL-2, IFN-γ, and granulocyte macrophage colony 
stimulating factor (GM-CSF), while suppressing the production of the Th2 cytokines IL-4 and 
IL-10 [16]. 
 
Pomalidomide exerts multiple effects on the immune system and also demonstrates anti-fibrotic 
activity in vivo [8].  Therefore, in addition to its beneficial activities in relapsed/refractory MM, 
pomalidomide provides a potentially new treatment alternative for conditions that possess altered 
immunological parameters related to inflammation, fibrosis, and Th2 response, such as 
scleroderma.  Pomalidomide also affects the regulation of fetal hemoglobin (hemoglobin F; 
[HbF]) expression by erythroid precursors from healthy adults as well as adults with sickle cell 
disease (SCD), making it a potential therapeutic agent for the treatment of nonmalignant 
hematologic disorders such as SCD and β-thalassemia. 
 
Nonclinical safety pharmacology studies showed no major safety concerns on cardiac function in 
dogs and monkeys, central nervous system (CNS) functions in rats, or respiratory functions in 
rats and monkeys [8]. 
 
In rats and monkeys, pomalidomide exhibited low systemic clearance and a moderate volume of 
distribution [8].  The oral bioavailability was dose dependent.  Following intravenous (IV) or 
oral administration of the enantiomers of pomalidomide, there was notable interconversion (18% 
to 32% based on area under the plasma concentration-time curve [AUC] ratios) between the 
enantiomers in monkeys. 
 
[14C]-pomalidomide-derived radioactivity was widely distributed into tissues in pigmented male 
rats, and moderate distribution of pomalidomide into the brain was observed in mice and rats [8].  
Pomalidomide was detected in fetal blood following administration to pregnant rabbits.  In 
lactating rats, pomalidomide was excreted into milk.  In rats, monkeys, and humans, the urinary 
excretion of metabolites was a major route of clearance for the absorbed fraction of [14C]-

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pomalidomide, while urinary excretion of unchanged drug was minor.  Intact pomalidomide 
represented a predominant portion of the circulating radioactivity in all species.  In rats, 
monkeys, and humans in vivo, as well as in vitro in human and rabbit hepatocytes, pomalidomide 
was metabolized via hydrolysis of the glutarimide and phthalidmide rings and hydroxylation of 
phthalimide aryl ring (with subsequent glucuronidation).  These data demonstrate similar 
metabolic pathways for pomalidomide in humans and animal species used in toxicity studies.  
 
Pomalidomide is not a cytochrome P (CYP) isoenzyme inhibitor or inducer, and did not inhibit 
any of the drug transporters evaluated, including P-glycoprotein, breast cancer resistant protein 
(BCRP), organic anion transporter protein (OATP)1B1, OATP1B3, organic anion transporters 
(OAT)1 and OAT3, and organic cation transporter (OCT)2, at clinically relevant concentrations 
in vitro studies [8]. 
 
Pomalidomide has a low potential for acute toxicity in rodents [8].  The minimum lethal doses 
after oral administration was >2000 mg/kg, and >80 mg/kg and >50 mg/kg after IV dosing in 
mice and rats, respectively.  Oral administration of pomalidomide to rats for 6 months was well-
tolerated at doses up to 1000 mg/kg/day, and this dose was established as the no-observed-
adverse-effect-level (NOAEL).  Oral administration of pomalidomide to monkeys for 9 months 
was well tolerated at 0.05 and 0.1 mg/kg/day, and 0.1 mg/kg/day was established as the NOAEL 
corresponding to the AUC over 24 hours (AUC24h) of 227, and 211 ng•hr/mL on Day 272 for 
males and females, respectively (approximately 0.5-fold exposure ratio relative to a 4 mg clinical 
dose).  In the 1 mg/kg/day dose, test article-related morbidity and early euthanasia (3/sex) were 
observed and were attributed to immunomodulation/immunosuppression (decreased peripheral 
lymphocytes, histologic lymphoid depletion, and hypocellularity of bone marrow).  These 
immunosuppressive effects were associated with staphylococcal infection and chronic 
inflammation of the large intestine.  Villous atrophy of the small intestine and minimal and mild 
bile duct proliferation were also present.  In addition, findings consistent with AML were 
observed in 1 of the females that was terminated early.  Evaluation of recovery animals indicated 
that all treatment related findings were reversible after 8 weeks of dosing cessation, except for 
proliferation of intrahepatic bile ducts observed in 1 animal in the 1.0 mg/kg/day group. 
 
In a fertility and early embryonic development study in rats, pomalidomide treatment of males 
and females resulted in a decrease mean number of viable embryos and an increase in post-
implantation loss at dosages of 25 mg/kg/day or higher [8].  These effects were not observed 
when treated males were mated with untreated females.  The NOAEL was <25 mg/kg/day 
(AUC24h was 39960 ng•h/mL at this lowest dose tested, and the exposure ratio was 99-fold 
relative to a 4 mg clinical dose).  Pomalidomide was found to be teratogenic in both rats and 
rabbits when administered during the period of major organogenesis.  The NOAELs for 
developmental toxicity were <25 mg/kg/day for rat (AUC24h was 34340 ng•h/mL on Gestation 
Day 17 at this lowest dose tested, and the exposure ratio was 85-fold relative to a 4 mg clinical 
dose) and <10 mg/kg/day for rabbit (AUC24h was 418 ng•h/mL on Gestation Day 19 at this 
lowest dose tested, which was similar to that obtained from a 4 mg clinical dose). 
 
Pomalidomide was also assessed for immunotoxicity in monkeys after treatment at 2 mg/kg/day 
for 28 days and had no impact on the innate immune system (granulocyte, monocyte, and NK 
cell function) [8].  However, effects on the adaptive immune system, including peripheral blood 

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lymphocyte depletion, alterations in humoral immune system, decreases in thymic weight, and 
general lymphoid depletion in lymphoid organs, were evident.  Most of the observed effects 
recovered or partially recovered after a 30-day drug-free period. 
 
Pomalidomide was not mutagenic in bacterial and mammalian cells and did not induce 
chromosomal aberrations in human peripheral blood lymphocytes or micronuclei formation in 
polychromatic erythrocytes in bone marrow of rats administered doses up to 2000 mg/kg/day [8].  
Carcinogenicity studies have not been conducted. 
2.2.1.3 
Clinical Studies  
 
The clinical program comprises safety and efficacy evaluations of pomalidomide for relapse or 
refractory MM, MMM, MPN-associated myelofibrosis, metastatic prostate cancer, advanced soft 
tissue sarcoma, small cell lung cancer, and non-oncology indication with SCD and SSc [8].  As 
of February 7, 2020, 26 studies using pomalidomide have been completed.  Over 30 clinical 
trials have been conducted (started, completed, and/or ongoing) across these therapeutic 
indications.  Across these studies, the pharmacokinetic (PK) profiles of single and multiple doses 
of pomalidomide from 0.5 mg to 50 mg, and 0.5 mg to 5 mg, respectively, have been evaluated 
in over 300 patients. 
 
2.2.1.4 
Clinical Pharmacology/Pharmacokinetic Studies  
 
2.2.1.4.1 
Human Pharmacokinetics (PK) 
 
As of February 7, 2020, 13 clinical studies have characterized the clinical pharmacology and 
biopharmaceutics of pomalidomide [8].  Pharmacokinetic data have been collected from 306 
patients who have received at least one dose of pomalidomide.  PK profiles of single and 
multiple doses of pomalidomide from 0.5 mg up to 50 mg, and 0.5 mg up to 5 mg, respectively, 
have been evaluated.  In general, the PK results were similar between healthy and MM patients. 
 
2.2.1.4.2 
Absorption 
 
Pomalidomide was absorbed in healthy patients under fasting conditions at single, orally 
administered doses of 0.5 to 50 mg with a maximum plasma concentration (Cmax) at a median 
time (tmax) of approximately 3 hours post dose [8].  The systemic exposure of single dose 
pomalidomide as determined from the AUC (AUC from time zero 
to the last measurable time point [AUC0-t] and AUC from time zero extrapolated to infinity 
[AUC0-∞]) increased in an approximately dose proportional manner, whereas Cmax increased in a 
proportional manner over 0.5 mg to 2 mg and in a less than dose proportional manner over the 1 
mg to 50 mg dose range.  Exploratory analysis suggests absorption rate decreases at doses 
greater than 10 mg.  Multiple dose exposure over the 0.5 mg to 2 mg dose range was 
approximately dose proportional, with pomalidomide reaching steady state by Day 3. 
 
2.2.1.4.3 
Distribution 
 
Mean (% coefficient of variation [CV]) apparent total volume of distribution when dosed orally 
(Vz/F) of pomalidomide in healthy patients after a single dose ranged from 74 L (20%) to 138 L 

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(30%) across a dose range of 1 mg to 10 mg daily [8].  Pomalidomide distributes into semen, 
with a geometric mean concentration of 16.4 ng/mL at 4 hours post-dose after 4 daily doses of 2 
mg.  This was approximately 67% of pomalidomide plasma concentration observed at the same 
time point on Day 5.  In vitro data indicate that pomalidomide protein binding in human plasma 
was low to moderate (15.8% for R-enantiomer, 42.2% for S-enantiomer) and the binding was 
concentration independent in the concentration range of 30 and 1000 ng/mL. 
 
2.2.1.4.4 
Metabolism 
 
A [14C]-pomalidomide study showed that the majority of circulating total radioactivity was 
associated with pomalidomide (~70%) [8].  Pomalidomide is a racemic mixture of R- and S-
enantiomers, CC-6016 and CC-5083, respectively.  The mean Cmax and AUC0-t values for CC-
6016 were approximately 49% and 50%, respectively, and for CC-5083 were approximately 52% 
and 49%, respectively, of those observed for pomalidomide in plasma, indicating that the R- and 
S-enantiomers were present in approximately equal amounts.  Eight metabolites were detected in 
plasma, each at exposures <10% of the plasma pomalidomide.  The metabolites observed were 
formed primarily via hydroxylation with subsequent glucuronidation, or hydrolysis of the parent 
compound.  CYP-dependent metabolites accounted for approximately 43% of the excreted 
radioactivity, while non-CYP dependent hydrolytic metabolites accounted for 25%, and 
excretion of unchanged pomalidomide accounted for 10%.  There were no unique or 
disproportionate metabolites observed in humans compared with in vivo data from rats and 
monkeys.  These metabolites have shown no or weak activity in MM cell proliferation screens 
and the immunomodulatory assays and are unlikely to contribute significantly to these 
pharmacological activities of the parent compound. 
 
2.2.1.4.5 
Elimination 
 
Pomalidomide is eliminated predominantly through renal excretion (~73% of the administered 
dose), with < 3% of the administered dose excreted in urine as unchanged pomalidomide across 
all dose levels, indicating extensive metabolism prior to excretion [8].  The radioactivity in feces 
(15.5% of the dose) contained parent compound (approximately 8% of the dose) and several 
metabolites.  The metabolites in excreta were formed via similar pathways as those observed in 
plasma.  Based on the in vivo rat, monkey and human metabolism data, there were no unique or 
disproportionate metabolites observed in humans.  The geometric mean terminal elimination 
half-life (t1/2) of pomalidomide was approximately 7.5 hours and the apparent total plasma 
clearance (CL/F) generally ranged from 6.5 to 10.8 L/hr.  CL/F and t1/2 in plasma appeared to be 
independent of dose and dosing duration. 
 
2.2.1.4.6 
Drug-Interactions 
 
As a substrate, since pomalidomide is eliminated in humans via multiple pathways (CYP 
mediated metabolism, enzymatic and non-enzymatic hydrolysis, and excretion of unchanged 
drug), and several CYP enzymes are capable of metabolizing pomalidomide, namely CYP1A2, 
CYP3A4, and to a minor extent CYP2C19 and CYP2D6, it is not anticipated that 
coadministration of an inhibitor or inducer of any one of these CYPs will have a significant 
impact on pomalidomide pharmacokinetics [8].  Co-administration with dexamethasone (a weak 

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to moderate inducer of several CYP enzymes including CYP3A) did not affect the PK profile of 
pomalidomide in MM patients.  Coadministration of a strong CYP1A2 inhibitor (fluvoxamine) 
with pomalidomide in the presence of a strong CYP3A4 inhibitor (ketoconazole) approximately 
doubled the mean exposure to pomalidomide compared to pomalidomide with ketoconazole 
alone.  If strong inhibitors of CYP1A2 (e.g., ciprofloxacin, enoxacin, and fluvoxamine) are 
coadministered with pomalidomide, patients should be closely monitored for the occurrence of 
side effects. 
Pomalidomide is a substrate of P-glycoprotein (P-gp).  P-gp in MDCK cells, although intestinal 
absorption did not appear to be limited by P-gp interaction (Investigator’s Brochure, 2020).  In 
the human absorption, metabolism and elimination (AME) study, at least 73% of the dose was 
absorbed, indicating good oral absorption.  Additionally, parent drug is the major circulating 
entity, and any effect of P-gp inhibition on the minor metabolites is unlikely to have any clinical 
impact.   
 
2.2.1.4.7 
Food Effects 
 
Two studies have assessed the effects of food on pomalidomide [8].  The median Tmax observed 
in the fed state was approximately 3 hours later than that observed in the fasted state.  Exposure 
to pomalidomide was slightly decreased with food.  The mean ratio estimates for Cmax and 
AUC0-t were 75.6% and 91.5% in the fed state relative to the fasted state.  The mean t1/2 of 
pomalidomide was not affected by food administration.  In summary, a high fat meal decreased 
the rate of absorption but had minimal effect on overall extent of absorption; therefore, 
pomalidomide can be administered without regard to food intake. 
 
2.2.1.5 
Safety and Efficacy Clinical Studies  
 
Pomalidomide was safe at doses of up to 50 mg in a phase 1 single dose study in normal, healthy 
male volunteers and the maximum tolerated dose (MTD) was determined to be 5 mg every other 
day (QOD) or 2 mg daily (QD) in a phase 1 multidose clinical study in patients with relapsed or 
refractory multiple myeloma (RRMM) [8].  Dose-limiting toxicities (DLTs) seen in patients 
receiving higher doses were predominantly hematopoetic (i.e., neutropenia), and lower grade, 
self-limited neutropenia was also seen in some of the 1 and 2 mg QD and 5 mg QOD recipients.  
In a multidose, phase 2 clinical study of patients with prostate cancer, 2 mg QD dosing was well 
tolerated and, unlike the MM patients who received 1 and 2 mg QD doses, only an overall shift 
to lower neutrophil counts was noted.  No clinically relevant neutropenic adverse events (AEs) 
were observed, and no grade 3 or 4 neutropenic events occurred.  It is, therefore, likely that 
patients with solid tumors that do not extensively involve the bone marrow will have a higher 
pomalidomide MTD than patients with hematologic malignancies. 
 
At tolerated doses (MTD=2 mg QD and 5 mg QOD), pomalidomide has been shown to be active 
in patients with relapsed or refractory MM [8, 24, 25].  In 45 patients who received doses of 
pomalidomide ranging, by cohort, up to 10 mg daily, the most commonly occurring DLT was 
reversible neutropenia.  As with other IMiDs administered to patients receiving concomitant 
systemic steroids, deep vein thrombosis (DVT) was seen (in one patient each in this study and in 
its subsequent named patient supply rollover program) [8, 26]. 
 

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Preliminary efficacy and safety data from an ongoing phase 2 study, led by Martha Lacy et al. 
(Mayo Clinic), were published [27, 28].  Sixty patients with relapsed or refractory MM were 
enrolled.  Pomalidomide was given orally at a dose of 2 mg daily on Days 1-28 of a 28-day cycle 
and dexamethasone was given orally at a dose of 40 mg daily on Days 1, 8, 15, 22 of each cycle.  
Patients also received aspirin 325 mg once daily for thromboprophylaxis.  The study endpoints 
were the response rate in patients taking pomalidomide plus dexamethasone, including patients 
with lenalidomide resistant refractory MM, and safety of pomalidomide plus dexamethasone.  
Responses were recorded using the criteria of the International Myeloma Working Group.  
Thirty-eight patients achieved objective response (OR) (63%) including CR in 3 patients (5%), 
very good partial response (VGPR) in 17 patients (28%), and partial response (PR) in 18 patients 
(30%).  The CR + VGPR rate was 33%. grade 3 or 4 hematologic toxicity occurred in 23 patients 
(38%) and consisted of anemia in three patients (5%), thrombocytopenia in two patients (3%) 
and neutropenia in 21 (35%).  Among those that developed grade 3/4 neutropenia, all first 
experienced the neutropenia in Cycle 1-3; no new patients experienced grade 3/4 neutropenia in 
Cycle 4 or later.  The most common non-hematological grade 3/4 toxicities were fatigue (17%) 
and pneumonia (8%).  Other grade 3/4 non-hematological toxicities that occurred in less than 5% 
included diarrhea, constipation, hyperglycemia, and neuropathy.  One patient (1.6%) had a 
thromboembolic event of deep vein thrombosis. 
 
Lacy et al. have also demonstrated promising clinical activity of pomalidomide in myeloma 
patients with persistent disease following lenalidomide treatment [28].  A Celgene sponsored 
phase 1b/2 multi-center, randomized, open-label, dose escalation study evaluated the MTD, 
safety and efficacy of oral pomalidomide alone and in combination with low-dose 
dexamethasone in patients with relapsed and refractory MM.  Eligible patients must have 
received at least 2 prior regimens and all patients must have received prior treatment that 
includes lenalidomide and bortezomib.  This study consisted of a phase 1 single agent 
pomalidomide MTD segment and phase 2 randomized (pomalidomide plus low-dose 
dexamethasone versus pomalidomide alone) segment. 
 
The MTD was 4 mg 21/28 days (there were 4 drug-related DLTs [grade 4 neutropenia] at 5 mg).  
Neutropenia and anemia were the most common grade 3/4 toxicities; there was a dose-dependent 
increase in grade 4 neutropenia.  Based on the safety and response data, 4 mg 21/28 days was the 
dose for the phase 2 segment [29].  Phase 2 of the study was designed to evaluate the efficacy 
and safety of pomalidomide at the MTD alone and in combination with low dose dexamethasone 
and enrolled 221 patients.  There were 113 pomalidomide + dexamethasone-treated patients and 
108 pomalidomide treated patients.  Median follow up was 14.2 months.  Reported outcomes 
results for the pomalidomide and dexamethasone versus the pomalidomide only groups included 
the following:  median PFS was 4.2 and 2.7 months (hazard ratio=0.68, P=.003), ORRs were 
33% and 18% (P=.013), median response duration was 8.3 and 10.7 months, and median OS was 
16.5 and 13.6 months, respectively.  The most common grade 3-4 toxicity was neutropenia (41% 
in pomalidomide and dexamethasone and 48% in pomalidomide alone) [30]. 
 
Pre-clinical data and the prior experience with thalidomide and lenalidomide in the treatment of 
patients with MMM provide the rationale for the use of pomalidomide in patients with MMM.  
This is further supported by the results of a Celgene sponsored trial which indicated that 
pomalidomide therapy at 0.5 mg or 2 mg/day +/- an abbreviated course of prednisone 30 mg is 

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well tolerated in patients with myelofibrosis and active in the treatment of anemia [31].  After a 
median treatment period of 4.6 months, the anemia response rates in four arms were 23% 
(pomalidomide 2 mg/placebo), 16% (pomalidomide/prednisone), 36% (pomalidomide 0.5 
mg/prednisone) and 19% (pomalidomide 0.5 mg/placebo).  Response was durable and ranging 
from 3.2 to 16.9 + months. 
 
Across the ongoing studies with available data, SAEs were reported by approximately 50% to 
60% of patients.  The safety profile in these studies may be expected in a population with 
advanced disease such as that participating in these studies and is consistent with that seen in the 
completed studies. 
 
2.3 
Other Agent 
 
2.3.1 Daunorubicin and cytarabine liposome 
 
Liposomal delivery systems for anthracyclines are a promising strategy to mitigate cardiotoxicity 
while maintaining efficacy [32-34].  The potential advantages of liposomal preparations include 
1) prolonged time in the circulation due to protection of the drug from enzymatic inactivation; 2) 
altered bio-distribution of the liposome formulation with potential sparing of normal tissue to 
mitigate toxicity; and 3) circumvention of drug efflux transporters responsible for drug resistance 
[35-38].  Daunorubicin and cytarabine liposome liposome for intravenous administration is a 
fixed combination of daunorubicin (44 mg) and cytarabine (100 mg) in a 1:5 molar ratio 
encapsulated in liposomes.  The liposome membrane is made of distearoylphosphatidylcholine 
(DSPC), distearoylphosphatidylglycerol (DSPG), and cholesterol in a 7:2:1 molar ratio. 
 
The 1:5 molar ratio of daunorubicin:cytarabine has been shown to have synergistic effects at 
killing leukemia cells in vitro and in murine models.   Daunorubicin has antimitotic and 
cytotoxic activity, which is achieved by forming complexes with DNA, inhibiting topoisomerase 
II activity, inhibiting DNA polymerase activity, affecting regulation of gene expression, and 
producing DNA-damaging free radicals.  Cytarabine is a cell cycle phase-specific antineoplastic 
agent, affecting cells only during the S-phase of cell division.  Cytarabine acts primarily through 
inhibition of DNA polymerase.  Based on animal data, the liposomes enter and persist in the 
bone marrow, where they are taken up intact by bone marrow cells.  In leukemia-bearing mice, 
the liposomes are taken up by leukemia cells to a greater extent than by normal bone marrow 
cells.  After cellular internalization, liposomes undergo degradation releasing cytarabine and 
daunorubicin within the intracellular environment. 
 
Based on positive phase 3 findings, daunorubicin and cytarabine liposome was approved by the 
FDA in August 2017 for the treatment of adults with newly diagnosed therapy-related AML or 
AML with MDS changes.  Prior studies have demonstrated the importance of ratio-dependent 
synergy and antagonism for combinations of cytarabine and daunorubicin.  Maintaining a fixed 
ratio is difficult when using combinations of free drugs given the different distribution, 
metabolism, and elimination properties of the individual drugs.  In preclinical models, 
daunorubicin and cytarabine liposome provided elevated and prolonged drug concentrations that 
were orders of magnitude higher than free drug and also higher daunorubicin concentrations 
compared to Daunoxome (DNX), a liposomal anthracycline.  When daunorubicin and cytarabine 

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liposome was given Days 1, 3, and 5 in the adult Phase 1 study, the clearance of cytarabine and 
daunorubicin was less than 120 mL/h/m2 across all dose levels.  This is markedly less than the 
clearance of unencapsulated daunorubicin (38,600 mL/h/m2) and cytarabine (134,000 mL/h/m2) 
and results in striking differences in plasma elimination half-life when comparing daunorubicin 
and cytarabine liposome with free drug or with DNX [39, 40].  Of interest, there is almost no 
distribution phase of daunorubicin and cytarabine liposome, suggesting that virtually all 
detectable daunorubicin and cytarabine liposome in the plasma exists in the encapsulated form.  
In addition, these concentrations are maintained in the circulation at the synergistic daunorubicin 
to cytarabine 1:5 ratio [41-43].  Therefore, CPX 351 accumulates and persists in the bone 
marrow at drug concentrations many fold higher than free drugs and significantly higher than 
DNX.  Further, liposome encapsulation may result in the drug being selectively taken up by the 
leukemia cells with subsequent release of cytarabine and daunorubicin from intracytoplasmic 
liposomes [41]. 
 
A number of studies of daunorubicin and cytarabine liposome have been conducted in both de 
novo and relapsed/refractory adult AML.  The adult Phase 1 study of daunorubicin and 
cytarabine liposome reported DLT at 134 units/m2.  The DLTs were persistent cytopenia > 56 
days (1 patient), congestive heart failure (CHF) (1 patient), and hypertensive crisis (1 patient) 
[44].  The episode of CHF occurred during a period of sepsis and was transient.  Two phase 2 
studies in adults demonstrated superior response rates and improved overall survival (OS) among 
patients with unfavorable risk features [7].  A randomized phase 3 study comparing daunorubicin 
and cytarabine liposome vs. 7+3 in older adults (60 to 75 years) with high-risk AML/MDS 
reported significantly improved complete response (CR) rates and OS in the daunorubicin and 
cytarabine liposome arm.  Importantly, 60-day mortality due to progressive AML was 
significantly different between the daunorubicin and cytarabine liposome (3.3%) and 7+3 cohorts 
(11.3%).  More patients treated with daunorubicin and cytarabine liposome received HSCT 
compared to those on the standard arm (34% daunorubicin and cytarabine liposome vs. 25% 
7+3).  An intent to treat OS analysis, landmarked at hematopoietic stem-cell transplantation 
(HSCT), demonstrated marked benefit for those randomized to the daunorubicin and cytarabine 
liposome arm (HR-0.46, p=0.0046).  Although MRD data was not collected, this would suggest 
that patients with daunorubicin and cytarabine liposome had lower disease burden at time of 
HSCT compared to those who received standard 7+3 chemotherapy.  The aforementioned 
clinical trial results in adults led to FDA approval of daunorubicin and cytarabine liposome for 
adult patients with newly diagnosed therapy-related AML or AML with MDS-related changes. 
 
Standard dosing will be used for daunorubicin and cytarabine liposome.  For induction, the dose 
is 44 mg/m2 daunorubicin and 100 mg/m2 cytarabine liposome IV infusion for 90 min on Days 1, 
3, and 5.  If needed, patients may undergo re-induction on Day 1 and 3 using the same dosing as 
the initial induction.  Dosing for consolidation will be 29 mg/m2 daunorubicin and 65 mg/m2 
cytarabine liposome IV infusion on days 1 and 3. 
 
2.4 
Rationale 
 
2.4.1 Rationale for Current Study Design: 
 
Multiple innate and adaptive immune system aberrations that promote leukemia immune escape 

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occur at diagnosis leading to immune suppression, exhaustion and senescence [45-47].  This 
immune dysfunction persists throughout disease progression in AML.  We and others have 
shown that co-inhibitory molecules and senescence markers are expressed by CD8+ T cells at 
diagnosis leading to T cell dysfunction [48-50].  Our recent analysis demonstrates that the 
dysfunctional phenotypic and transcriptional signatures of CD8+ T cells are reversed in patients 
who achieve CR in contrast to non-responders, suggesting that immune modulation may provide 
benefit for patients who have not responded to intensive chemotherapy [48].  One of the 
predominant mechanisms of immune dysfunction in AML is related to the dysregulation of 
regulatory T cells (Tregs). Tregs are increased in the peripheral blood and bone marrow of AML 
patients [51-53], exhibit immunosuppressive effects on T effector cells [53], are minimally 
affected by chemotherapy [54], and are associated with worse outcomes in AML [52].  Our 
group demonstrated that early lymphocyte recovery (ELR), defined by the total white blood cell 
(WBC) count reaching ≥0.2x109/L above nadir, and customarily occurring between Days 14-21 
of timed-sequential induction therapy (TST), is dominated by an expanded oligoclonal 
population of peripherally-derived Tregs [55].  These findings provided the impetus for a CTEP-
sponsored phase 1 dose escalation study of pomalidomide, a potent immunomodulatory agent, 
administered at the time of ELR after induction TST in newly diagnosed AML and high-risk 
MDS.  Through its interaction with cereblon, a substrate receptor for the E3 ubiquitin ligase 
complex, pomalidomide leads to the selective ubiquitination of transcription factors Ikaros and 
Aiolos thereby increasing IL-2 production [10]. 
 
In this phase 1 study, all patients received TST with AcDVP16 (cytarabine 667 mg/m2/day 
continuous infusion [CI] IV Days 1-3, daunorubicin 45 mg/m2 IV Days 1-3 [or idarubicin 8 
mg/m2 during daunorubicin shortage], and etoposide 400 mg/m2 IV Days 8-10).  Pomalidomide 
was administered orally at the time of ELR, after Day 14 of induction therapy and within 3 days 
of ELR, but no later than Day 30 of induction therapy (median Day 21) to 43 patients with newly 
diagnosed AML with non-favorable cytogenetics (n=39) and high-risk MDS (n=4).  The MTD of 
pomalidomide was 4 mg for 21 days at ELR.  Pomalidomide was well tolerated and drug-related 
grade ≥3 toxicities are shown in Table 1.  Of those treated with AcDVP16 + pomalidomide, 33 
(77%) patients achieved a CR/CRi (Table 2).  Subset analyses revealed an encouraging CR rate 
in those with secondary AML (71% CR), AML with MDS-related changes (MRC: 85% CR), and 
those with unfavorable-risk cytogenetics (82% CR).  Laboratory correlates from samples 
obtained from patients on this study revealed that pomalidomide significantly decreased Aiolos 
expression, induced T cell differentiation, proliferation and cytokine production, and led to 
distinct gene expression changes in immune function-related ontologies in CD4+ and CD8+ T 
cells [56].  
 
Table 1:  Non-hematologic grade ≥3 toxicities possibly related to pomalidomide 
Adverse Event 
2 mg x 10 
days 
(n=3) 
4 mg x 
10 days 
(n=3) 
8 mg x 10 
days 
(n=7) 
4 mg x 
21 days 
(n=25) 
8 mg x 21 
days 
(n=5) 
Infectious 
  Febrile neutropenia 
  Lung infection 
  Sepsis 
 
 
1 
 
 
3 
 
5 
1 
1 
 
1 

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Electrolyte Abnormalities 
  Hypokalemia 
Hepatic 
  ALT elevation 
  AST elevation 
 
 
 
 
1 
 
1 
 
 
 
 
1 
1 
Pulmonary 
   Hypoxia 
   Respiratory Failure 
 
 
 
 
1 
 
 
1 
Renal 
   Acute kidney injury 
 
 
 
 
1 
 
General 
   Fatigue 
   Maculo-papular rash 
 
 
 
 
 
 
1 
5 
 
 
1 
 
 
 
 
Table 2:  Summary of response characteristics 
Response characteristics 
MDS 
(n = 4) 
AML 
(n = 39) 
Overall pom-
treated 
Not treated 
with pom 
Overall 
evaluable 
 
 
(n = 43) 
(n = 8) 
(n = 51) 
CR 
3 (75%) 
28 (72%) 
31 (72%) 
4 (50%) 
35 (69%) 
CRi 
0 
2 (5%) 
2 (5%) 
1 (13%) 
3 (6%) 
Overall CR 
3 (75%) 
30 (77%) 
33 (77%) 
5 (63%) 
38 (75%) 
Overall CR subgroups 
 
 
 
 
 
Secondary AML 
N/A 
10/14 (71%) 
10/14 (71%) 
2/3 (67%) 
12/17 (71%) 
AML with MDS-related 
N/A 
11/13 (85%) 
11/13 (85%) 
2/4 (50%) 
13/17 (76%) 
changes 
 
 
 
 
 
<60 years 
2/3 (67%) 
21/28 (75%) 
23/31 (74%) 
2/3 (67%) 
25/34 (74%) 
>60 years 
1/1 (100%) 
9/11 (82%) 
10/12 (83%) 
3/5 (60%) 
13/17 (76%) 
ELN-risk (Dohner et al.,2017) 
 
 
 
 
 
Favorable 
N/A 
9/9 (100%) 
9/9 (100%) 
1/1 (100%) 
10/10 (100%) 
Intermediate 
N/A 
12/17 (71%) 
12/17 (71%) 
1/2 (50%) 
13/19 (68%) 
Adverse 
N/A 
9/13 (69%) 
9/13 (69%) 
3/4 (75%) 
12/17 (71%) 
SWOG cytogenetics risk [57] 
Favorable 
N/A 
N/A 
N/A 
N/A 
N/A 
Intermediate 
1/1 
16/23 (70%) 
17/25 (68%) 
3/3 (100%) 
20/28 (71%) 
Unfavorable 
2/3 (67%) 
12/14 (86%) 
14/17 (82%) 
2/4 (50%) 
16/21 (76%) 
Unknown 
N/A 
2/2 (100%) 
2/2 (100%) 
0/1 (0) 
2/3 (67%) 
4 mg × 21 days (MTD) 
3/4 (75%) 
15/21 (71%) 
18/25 (72%) 
N/A 
18/25 (72%) 
AML patient characteristics 
AcDVP16 historical controls 
n = 301 (6) 
AcDVP16 + pomalidomide 
n = 39 
Median age (range) 
52 (20–74) 
54 (21–65) 
Overall CR/CRi 
205/301 (68%) 
30/39 (77%) 
Age ≥ 60 years 
45/79 (57%) 
9/11 (82%) 
Secondary AML 
51/96 (53%) 
10/14 (71%) 
Cytogenetic classiﬁcation 
Intermediate 
133/180 (74%) 
16/23 (70%) 

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Unfavorable 
49/94 (52%) 
12/14 (86%) 
Non-favorable 
182/274 (66%) 
28/37 (76%)a 
Allogeneic SCT 
98/301 (33%) 
23/39 (59%) 
Median OS 
17.2 months 
33.8 months 
Median OS-unfavorable- 
8.2 months 
19.7 months 
risk cytogenetics 
Median DFS 
15.0 months 
27.1 months 
Median DFS-unfavorable- 
9.2 months 
8.2 months 
risk cytogenetics 
aTwo patients had unknown cytogenetic risk per SWOG classiﬁcation and were thus excluded for comparison to 
overall non-favorable risk. 
 
Given the poor outcomes of patients with AML with MRC and the promising findings seen in 
this patient population in the phase 1 study, a randomized phase 2 study investigating the 
addition of pomalidomide to standard-of-care daunorubicin and cytarabine liposome in newly 
diagnosed AML with MRC is warranted to determine whether pomalidomide is an effective 
immunomodulatory adjunct after induction chemotherapy in patients with AML with MRC. 
 
2.4.2 Justification of Pomalidomide Dose and Schedule 
 
In the Phase 1 study of AcDVP16 followed by dose escalation of pomalidomide at ELR, 
pharmacodynamic (PD) analysis was performed by assessing pomalidomide’s impact on Aiolos 
inhibition in CD4+ and CD8+ T cells by flow cytometry. In the initial cohort of pomalidomide 
dose escalation of 2 mg, 4 mg and 8 mg for 10 consecutive days at ELR, there was more robust 
Aiolos inhibition seen at the 4 mg and 8 mg doses when compared with 2 mg dose[58]. 
Additionally, there were no significant differences observed in Aiolos inhibition between the 4 
mg and 8 mg doses (Figure 1).  
 
Figure 1. Ailos Expression in CD4+ and CD8+ T cells with Increasing Pomalidomide Exposure. 
 
 
 
Further, Aiolos expression was suppressed during pomalidomide administration only and 
returned to normal/baseline levels within 1 week after discontinuation of pomalidomide (Figure 
2). These observations signified that the duration of pomalidomide exposure is most critical to 
achieve a PD effect. As such, pomalidomide dosing regimen of 4 mg for 21 consecutive days at 
ELR was established as the MTD and schedule after AcDVP16 induction (Table 1)  [56] 

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consistent with the FDA approved pomalidomide dose in multiple myeloma. 
 
2.4.3 
Rationale for Safety Run-In   
 
The MTD of pomalidomide after AcDVP16 TST was 4 mg for 21 consecutive days at ELR. 
However, pomalidomide has not been investigated after daunorubicin and cytarabine liposome 
induction therapy. Thus, a safety run-in will be performed prior to randomization to determine 
the optimal schedule of pomalidomide after daunorubicin and cytarabine liposome induction. 
Two dosing schedules of pomalidomide will be explored in a safety run-in: 4 mg for 14 days 
versus 4 mg for 21 days. The recommended phase 2 dose/duration will then be used in the 
randomized phase 2 portion of the study after an evaluation of safety and tolerability data, 
efficacy, anti-tumor activity, exposure and PD effects, if available, in both cohorts.  
 
Ultimately, we hypothesize that the addition of pomalidomide starting on day 21 of daunorubicin 
and cytarabine liposome induction therapy for patients with newly diagnosed AML with 
preexisting MDS, CMML or MPN, or AML with MRC based on cytogenetics or morphologic 
dysplasia without history of MDS/MPN, will lead to an improvement in CR/CRi rate compared 
with daunorubicin and cytarabine liposome alone.  
 
Figure 2 Aiolos Expression Prior to, During and After Pomalidomide Administration 
 
 
2.5 
Correlative Studies Background 
 
2.5.1 Integrated Correlative Studies 
 

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2.5.1.1 
Foundation One Heme panel (Next Generation Sequencing Myeloid  
Mutational Panel) 
 
It is standard-of-care to perform next generation sequencing (NGS) mutational panels on newly 
diagnosed AML patients to inform risk stratification and overall prognosis.  Although there are a 
number of different laboratories and panels that are used for this assessment, it is critical to have 
a homogeneous and reproducible results with one uniform, comprehensive assay for a 
multicenter randomized trial.  The Foundation One Heme NGS panel is a comprehensive 
genomic assay that interrogates 406 genes for four classes of alterations: single nucleotide 
variants, small insertions/deletions, copy number variants, and gene fusions.  These results will 
be used to compare responders (i.e. CR/CRi) versus non-responders to determine if there is a 
molecular signature associated with response to pomalidomide.  The NGS mutational panel is 
strongly recommended for all patients and bone marrow aspirates if NGS has not been performed 
prior to consent in order to have uniform results across all institutions. If NGS has been 
performed by an alternative laboratory within 30 days of consent, Foundation One Heme testing 
is still strongly recommended for uniform NGS testing but not required. Please notify the PI for 
discussion if Foundation One Heme Panel is not planning on being performed. Foundation One 
Heme will be collected prior to pre-treatment in both arms. Foundation One Heme Panel should 
be sent with clinical information and without study identification.  
 
 
2.5.1.2 
Aiolos Expression (Flow Cytometry) 
 
Aiolos expression in T cells will be assessed by flow cytometry from bone marrow aspirate and 
peripheral blood samples prior to treatment with daunorubicin and cytarabine liposome +/- 
pomalidomide, during pomalidomide administration (Days 14 and 28), and at recovery.  
Determination of T cell expression of Aiolos is mandatory for all patients.  The role of this assay 
is to determine whether Aiolos expression prior to treatment with daunorubicin and cytarabine 
liposome + pomalidomide and during pomalidomide administration is associated with response 
and clinical outcomes and will be compared with the Aiolos expression in the control arm 
samples collected at the same time points.  The Aiolos expression will be examined in context 
with other T cell markers, to better delineate T cell differentiation and expression of co-signaling 
molecules and changes induced by pomalidomide administration. 
 
Aiolos expression in T cells will be assessed in UNC and John Hopkins University (JHU) 
participants only. All other affiliate site participants are exempt. 
 
2.5.1.3 
Hematologics Measurable Residual Disease (MRD) Assay (Flow Cytometry and 
PCR-based) 
 
In patients on both arms, MRD will be assessed by standardized flow cytometry assessment at 
the time of response by Hematologics, Inc. and PCR-based methodologies as standard of care.  
Neoplastic cells are distinguished from normal counterparts by multiparameter flow cytometry 
using a combination of difference from normal and leukemia-associated immunophenotype 
approaches, both of which allow sensitive detection of disease population based on abnormal 
expression of cellular antigens.  Sensitivity is generally estimated at 0.5% or less of total 

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nucleated cells.  This assay will be used uniformly to assess for MRD in patients receiving 
pomalidomide versus control group.  Bone marrow aspirate collection is mandatory for all 
patients and will be collected pre-treatment and at response. Hematologics MRD should be sent 
with clinical information and without study identification. 
 
2.5.2 Exploratory/Ancillary Correlative Studies 
 
2.5.2.1 
T-cell subsets (Flow Cytometry) 
 
The purpose of the T-cell subsets assay is to assess whether pre-treatment expression of T-cell 
subsets (in blood vs. bone marrow) are associated with response to daunorubicin and cytarabine 
liposome + pomalidomide, as well as to assess whether pomalidomide can induce changes in T 
cell composition in responders versus non-responders.  Bone marrow aspirate collection is 
mandatory for all patients and will be collected pre-treatment, Day 14, Day 28 and at response. 
 
T-cell subsets will be assessed in UNC and JHU participants only. All other affiliate site 
participants are exempt. 
 
2.5.2.2 
RNA Sequencing of blasts (NGS) 
 
mRNA-sequencing (mRNA-seq) of bulk bone marrow leukocyte samples from diagnostic 
samples and at response will be performed to assess for genetic subtypes and evaluation of gene 
expression signatures associated with immune activation and suppression in responders (i.e. 
CR/CRi) versus non-responders.  mRNA-seq is mandatory for all patients and bone marrow 
aspirates will be collected prior to treatment and at the response assessment in both arms. 
 
2.5.2.3 
T cell receptor repertoire analysis 
 
T cell receptor beta (TCRβ) will be amplified using mRNA isolated from CD8 + T cells in the 
peripheral blood.  Following reverse transcription and cDNA amplification by PCR (using 
primers with unique sequence tags to minimize amplification bias), Illumina MiSeq sequencing 
libraries will be prepared by PCR ligation of barcoded sequencing adapters.  Sequence data will 
be processed and TCRβ sequences analyzed.  Each clonotype will be defined by a given variable 
gene (V), joining gene (J), and complementary determining region 3 (CDR3) usage.  Repertoires 
will be evaluated V/J gene usage, CDR3 length, charge, hydrophobicity, and amino acid motifs, 
frequency of dominant clonotypes, shared clonotypes, and overall population diversity.  Motif 
analysis will be done using the TEIRISIAS algorithm.  Shannon entropy will be used as the 
index of diversity and estimated with confidence intervals for comparison of multiple 
populations as previously described.  The Kruskal-Wallis test with Dunn’s post-tests will be used 
to compare clonal diversity, sharing of specific sequence motifs, and IgHV mutation rate 
between responders vs. non-responders.  Proportional hazards modeling and multivariate 
regression will be used to uncover relationships between continuous outcomes (DFS, OS) and 
repertoire characteristics. 
 
T cell receptor repertoire analysis is mandatory for all patients and peripheral blood will be 
collected pre-treatment, Day 21 (for Arm A, this should be before pomalidomide) and at 

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response.  The purpose of this assay is to determine whether pre-treatment TCR diversity is 
associated with response to daunorubicin and cytarabine liposome + pomalidomide vs. 
daunorubicin and cytarabine liposome alone. 
 
2.5.3 DNA sequencing for mutation detection at complete remission 
 
A DNA sequencing panel allowing detection of mutations present at pre-treatment will be used 
to assess for MRD by NGS to determine the proportion of patients who achieve an NGS MRD-
negative CR after daunorubicin and cytarabine liposome + pomalidomide versus daunorubicin 
and cytarabine liposome alone.   DNA isolated from bone marrow aspirates and/or blood 
collected at response assessment in both arms will be banked for this purpose.  Patients for 
whom the Foundation One Heme panel (Section 2.5.1.1) on pre-treatment marrow aspirate does 
not identify appropriate mutations for such tracking may undergo additional sequencing on DNA 
stored from pre-treatment bone marrow aspirate.  Sequencing will be performed in a single batch 
at the completion of the study, is for research purposes only and no results will be returned to 
patients.  
 
3. 
PATIENT SELECTION 
 
3.1 
Eligibility Criteria  
 
3.1.1 Pathological confirmation of AML as defined by histologic, morphologic, or cytological 
evidence/confirmation of ≥20% blasts in bone marrow aspirate and/or biopsy. 
 
3.1.2 Must meet criteria for t-AML or AML with MRC as defined by the 5th Edition of the 
World Health Organization (WHO ) [59] Classification of Myeloid Neoplasms or the 
International Consensus Classification (ICC) of Myeloid Neoplasms [60]. Patients must 
meet one of the following criteria: 
o 1) Therapy-related AML (AML derived from prior chemotherapy or radiation 
therapy) 
o 2) AML originating from prior hematologic malignancy (MDS, CMML, or MPN) 
o 3) AML with myelodysplasia-related cytogenetic abnormalities: 
▪ One of the following cytogenetic abnormalities: 
• Complex karyotype (3 or more unrelated chromosomal 
abnormalities in the absence of other class-defining recurrent 
genetic abnormalities as defined by WHO or ICC) 
• -7/del(7q) 
• Del(5q)/t(5q)/add(5q) 
• +8 
• i(17q) 
• -17/add(17p) or del(17p) 
• Del(20q) 
• -13/del(13q) 
• Del(11q) 
• Del(12p)/t(12p)/add(12p) 
• idicX(q13) 

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o 4) AML with Myelodysplasia-related mutations: Must have a mutation in one of 
the following genes: 
▪ ASXL1 
▪ BCOR 
▪ EZH2 
▪ RUNX1 
▪ SF3B1 
▪ SRSF2 
▪ STAG2 
▪ U2AF1 
▪ ZRSR2 
 
3.1.3 No prior treatment for AML other than cytoreductive doses of hydroxyurea or 
leukapheresis.   
 
3.1.4 Age ≥18 and <75 years on day of signing informed consent are eligible who are planned 
for intensive chemotherapy.  Because no dosing or adverse event data are currently 
available on the use of pomalidomide in combination with daunorubicin and cytarabine 
liposome in patients <18 years of age, children are excluded from this study.  Patients 
>75 years are not candidates for intensive chemotherapy with daunorubicin and 
cytarabine liposome.  
 
3.1.5 ECOG Performance Status of 0-2 (Karnofsky ≥60%, see Appendix A). 
 
3.1.6 Patients must have adequate organ and marrow function as defined below: 
 
− 
total bilirubin 
 
≤1.5 institutional upper limit of normal (ULN) 
unless due to leukemic infiltration, Gilbert’s 
Syndrome, or hemolysis 
− 
AST(SGOT)/ALT(SGPT) 
 
≤5 × institutional ULN 
− 
creatinine  
 
>30 ml/min creatinine clearance by cockroft-gault  
 
3.1.7 Left Ventricular ejection fraction (LVEF) ≥50%  
 
3.1.8 Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral 
therapy with undetectable viral load within 6 months are eligible for this trial.   
 
3.1.9 For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral 
load must be undetectable on suppressive therapy, if indicated. 
 
3.1.10 Patients with a history of hepatitis C virus (HCV) infection must have been treated and 
cured with undetectable HCV viral load.  For patients with HCV infection who are 
currently on treatment, they are eligible if they have an undetectable HCV viral load. 
 
3.1.11 Patients with known history or current symptoms of cardiac disease, or history of 
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac 

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function using the New York Heart Association Functional Classification.  To be eligible 
for this trial, patients should be class 2B or better. 
 
3.1.12 Females of childbearing potential (FCBP), defined as a female who: 1) has reached 
menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; 
or 3) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has 
had menses at any time in the preceding 24 consecutive months) must have a negative 
pregnancy test 72 hours prior to the start of study therapy.  For FCBPs in Arm A, they 
must have a negative serum or urine pregnancy test with a sensitivity of at least 25 
mIU/mL within 10 – 14 days prior to and again within 24 hours of starting pomalidomide 
and must either commit to continued abstinence from heterosexual intercourse or begin 
TWO acceptable methods of birth control, one highly effective method and one 
additional effective method AT THE SAME TIME, at least 28 days before starting 
pomalidomide.  FCBP must also agree to ongoing pregnancy testing.  Men must agree to 
use a latex condom during sexual contact with a FCBP even if they have had a 
vasectomy.  All patients must be counseled at a minimum of every 28 days about 
pregnancy precautions and risks of fetal exposure.  See Appendix D Pomalidomide Risks 
of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods, 
AND also Appendix E: Pomalidomide Education and Counseling Guidance Document. 
 
3.1.13 Ability to understand and the willingness to sign a written informed consent document.  
Participants with impaired decision-making capacity (IDMC) who have a legally-
authorized representative (LAR) and/or family member available will also be eligible. 
 
3.2 
Exclusion Criteria 
 
3.2.1 Patients with Wilson’s Disease or Copper-related metabolic disorders. 
 
3.2.2 Absolute blast count >30 x 109/L (cytoreduction with leukapheresis or hydroxyurea can 
be used to achieve absolute blast count <30 x 109/L prior to Day 1 of treatment).   
 
3.2.3 Cumulative daunorubicin lifetime exposure >330 mg/m2 and >180 mg/m2 with prior 
mediastinal radiation therapy.  
 
3.2.4 Patients with known active central nervous system leukemia should be excluded from this 
clinical trial because they often develop progressive neurologic dysfunction that would 
confound the evaluation of neurologic and other adverse events.  Patients receiving 
intrathecal chemotherapy prophylaxis should receive pomalidomide ≥3 days after 
administration. 
 
3.2.5 Patients with uncontrolled intercurrent illness including, but not limited to, active and 
uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, 
and cardiac arrhythmia.  Patients with infection under active treatment and controlled 
with antibiotics are eligible. 
 
3.2.6 Known additional malignancy (with the exception of prior hematologic malignancies that 

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have transformed to AML) that is active and/or progressive requiring treatment; 
exceptions include basal cell or squamous cell skin cancer, in situ cervical cancer or 
patients receiving maintenance treatments without active disease (for example, hormonal 
therapy for breast cancer or prostate cancer or other adjuvant chemotherapy approaches). 
Anti-cancer therapy as above should be discontinued >72 hours prior to Day 1 of 
treatment.   
 
3.2.7 Patients with psychiatric illness/social situations that would limit compliance with study 
requirements. 
 
3.2.8 Receipt of prior allogeneic stem cell transplant. 
 
3.2.9 Administration of any therapy for MDS, CMML, or MPN (conventional or 
unconventional) must be completed by 2 weeks prior to treatment with daunorubicin and 
cytarabine liposome.  Use of strong CYP1A2 inhibitors should be avoided. 
 
3.2.10 Patients who are receiving any other investigational agents. 
 
3.2.11 History of allergic reactions attributed to compounds of similar chemical or biologic 
composition to pomalidomide (e.g. lenalidomide, thalidomide) or daunorubicin and 
cytarabine liposome or their excipients. 
 
3.2.12 Development of erythema nodosum if characterized by a desquamating rash while taking 
thalidomide, lenalidomide, or similar drugs in the past. 
 
3.2.13 Pregnant women are excluded from this study because pomalidomide is an 
immunomodulatory agent with the potential for teratogenic or abortifacient effects.  
Because there is an unknown but potential risk for adverse events in nursing infants 
secondary to treatment of the mother with pomalidomide, breastfeeding should be 
discontinued if the mother is treated with pomalidomide.  These potential risks may also 
apply to other agents used in this study.  Women of childbearing potential must be 
willing to undergo pregnancy testing as outlined in the Time and Events Tables, Sections 
11.1 and 11.2. 
 
3.2.14 Any other medical condition that in the opinion of investigator would place patient at 
increased risk for toxicity during pomalidomide treatment (i.e. history of recurrent or 
serious thromboembolic events such as massive pulmonary embolism [see Section 
6.2.7]). 
 
3.3 
Inclusion of Women and Minorities 
 
NIH policy requires that women and members of minority groups and their subpopulations be 
included in all NIH-supported biomedical and behavioral research projects involving NIH-
defined clinical research unless a clear and compelling rationale and justification establishes to 
the satisfaction of the funding Institute & Center (IC) Director that inclusion is inappropriate 
with respect to the health of the patients or the purpose of the research.  Exclusion under other 

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CTEP and Cancer Trials Support Unit (CTSU) websites and applications.  In addition, IVRs and 
NPIVRs must list all clinical practice sites and Institutional Review Boards (IRBs) covering their 
practice sites on the FDA Form 1572 in RCR to allow the following: 
 
• Addition to a site roster, 
• Assign the treating, credit, consenting, or drug shipment (IVR only) tasks in OPEN, 
• Act as the site-protocol Principal Investigator (PI) on the IRB approval, and 
• Assign the Clinical Investigator (CI) role on the Delegation of Tasks Log (DTL).  
 
In addition, all investigators acting as the Site-Protocol PI (Investigator listed on the IRB 
approval), consenting/treating/drug shipment investigator in OPEN, or as the Clinical 
Investigator (CI) on the DTL must be rostered at the enrolling site with a participating 
organization.  
 
Additional information is located on the CTEP website at 
https://ctep.cancer.gov/investigatorResources/default.htm.  For questions, please contact the 
RCR Help Desk by email at RCRHelpDesk@nih.gov. 
 
 

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4.2 
Site Registration 
 
This study is supported by the NCI Cancer Trials Support Unit (CTSU). 
 
IRB Approval   
 
Sites participating with the NCI Central Institutional Review Board (NCI CIRB) must submit the 
Study Specific Worksheet (SSW) for Local Context to the CIRB using IRB Manager to indicate 
their intent to open the study locally.  The NCI CIRB’s approval of the SSW is automatically 
communicated to the CTSU Regulatory Office, but sites are required to contact the CTSU 
Regulatory Office at CTSURegPref@ctsu.coccg.org to establish site preferences for applying 
NCI CIRB approvals across their Signatory Network.  Site preferences can be set at the network 
or protocol level.  Questions about establishing site preferences can be addressed to the CTSU 
Regulatory Office by email or calling 1-888-651-CTSU (2878). 
 
In addition, the Site-Protocol PI (i.e., the investigator on the IRB/REB approval) must meet the 
following criteria to complete processing of the IRB/REB approval record to be completed: 
• Holds an active CTEP status, 
• Active status at the site(s) on the IRB/REB approval (applies to US and Canadian sites 
only) on at least one participating organization’s roster, 
• If using NCI CIRB, active on the NCI CIRB roster under the applicable CIRB Signatory 
Institution(s) record, 
• Includes the IRB number of the IRB providing approval in the Form FDA 1572 in the 
RCR profile, 
• Lists all sites on the IRB/REB approval as Practice Sites in the Form FDA 1572 in the 
RCR profile; and 
• Holds the appropriate CTEP registration type for the protocol.  
 
Additional Requirements 
 
Additional site requirements to obtain an approved site registration status include: 
• An active Federalwide Assurance (FWA) number, 
• An active roster affiliation with the Lead Protocol Organization (LPO) or a Participating 
Organization (PO), 
• An active roster affiliation with the NCI CIRB roster under at least one CIRB Signatory 
Institution (US sites only); and 
• Compliance with all protocol-specific requirements (PSRs). 
 
4.2.1 Downloading Site Registration Documents 
 
Download the site registration forms from the protocol-specific page located on the CTSU 
members’ website.  Permission to view and download this protocol and its supporting documents 
is restricted to institutions and its associated investigators and staff  on a participating roster.  To 
view/download site registration forms: 
 

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• Log in to the CTSU members’ website (https://www.ctsu.org) using your CTEP-IAM 
username and password, 
• Click on Protocols in the upper left of the screen 
o Enter the protocol number in the search field at the top of the protocol tree, or 
o Click on the By Lead Organization folder to expand, then select LAO-OH007, and 
protocol number 10434. 
• Click on Documents, Protocol Related Documents, and use the Document Type filter and 
select Site Registration, download and complete the forms provided.  (Note:  For sites 
under the CIRB, IRB data will load automatically to the CTSU.)  
 
4.2.2 Protocol Specific Requirements for NCI Protocol 10434 Site Registration 
 
• Completion of Site Initiation Visit to be completed before the first patient enrollment at a 
given site. 
• Specimen Tracking System Training Requirement: 
o All data entry users (Clinical Research Associate role) at each participating site will 
need to complete the Theradex-led training. 
o Theradex will provide a certificate of completion, which will need to be submitted to 
the CTSU through the Regulatory Submission Portal. 
o The training is a one-time only requirement per individual.  If an individual has 
previously completed the training for another ETCTN study, the training does not 
need to be completed again nor does the certificate of completion need to be 
resubmitted to the CTSU.  However, new versions of the Specimen Tracking System 
may require new training. 
o This training will need to be completed before the first patient enrollment at a given 
site. 
o Please contact STS Support at Theradex for the training 
(STS.Support@theradex.com, Theradex phone: 609-799-7580). 
 
4.2.2.1 
Site Registration Protocol Specific Requirement 
Each site must have two trained counselors available for counseling all patients receiving 
pomalidomide supplied by the Division of Cancer Treatment and Diagnosis.  Trained counselors 
must complete training using the online program provided free by Celgene, the Celgene 
Pregnancy Prevention Counseling Program (CPPCP).  Registration for the program is done by 
completing the form found in Appendix G and following the directions provided in the email 
notification.  After the training is complete, the counselors must generate a training certificate 
and provide it to the CTSU for documentation.  Sites may not order pomalidomide until 
documentation for two trained counselors is provided to the appropriate office. 
 
4.2.3 Submitting Regulatory Documents 
 
Submit required forms and documents to the CTSU Regulatory Office using the Regulatory 
Submission Portal on the CTSU members’ website.  
 
To access the Regulatory Submission Portal, log on to the CTSU members’ website, go to the 

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Regulatory section, and select Regulatory Submission. 
 
Institutions with patients waiting that are unable to use the Regulatory Submission Portal should 
alert the CTSU Regulatory Office immediately by phone or email: 1-866-651-CTSU (2878), or 
CTSURegHelp@coccg.org in order to receive further instruction and support. 
 
Delegation of Tasks Log (DTL) 
 
Each site must complete a protocol-specific DTL using the DTL application in the Delegation 
Log section on the CTSU members’ website.  The Clinical Investigator (CI) is required to review 
and electronically sign the DTL prior to the site receiving an approved site registration status and 
enrolling patients to the study.  To maintain an approved site registration status the CI must re-
sign the DTL at least annually and when a new version of the DTL is released; and activate new 
task assignments requiring CI sign-off.  Any individual at the enrolling site on a participating 
roster may initiate the site DTL.  Once the DTL is submitted for CI approval, only the designated 
DTL Administrators or the CI may update the DTL.  Instructions on completing the DTL are 
available in the Help Topics button in the DTL application and include a Master Task List, 
which describes DTL task assignments, CI signature, and CTEP registration requirements. 
 
4.2.4 Checking Site Registration Status 
 
Site’s registration status may be verified on the CTSU website.  
 
• Click on Regulatory at the top of the screen, 
• Click on Site Registration, and  
• Enter the site’s 5-character CTEP Institution Code and click on Go. 
o Additional filters are available to sort by Protocol, Registration Status, Protocol 
Status, and/or IRB Type. 
 
Note:  The status shown only reflects institutional compliance with site registration requirements 
as outlined within the protocol.  It does not reflect compliance with protocol requirements for 
individuals participating on the protocol or the enrolling investigator’s status with NCI or their 
affiliated networks. 
 
4.3 
Patient Registration 
 
Prior to registering patients into Oncology Patient Enrollment Network (OPEN), participating 
sites are instructed to contact the Coordinating Center for the following:  
• Subject Consent – Within 24 business hours of subject signing consent for the study, the 
Site Coordinator notifies the Project Manager by email (CPOMulticenter@med.unc.edu) 
with a completed new patient registration form and copies of consent. 
• Eligibility Confirmation – After completion of all screening evaluations and if possible, 
within at least 48 business hours of anticipated study treatment start, the Site Coordinator 
notifies the Project Manager by email (CPOMulticenter@med.unc.edu) and includes the 
completed eligibility checklist and de-identified supporting source documentation. After 

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review of eligibility documents by the Lead Principal Investigator or designee(s), the 
Project Manager will email the Site Coordinator with confirmation or 
questions/comments regarding subject eligibility. If eligibility is confirmed, the Site 
Coordinator will be instructed by the Project Manager via email to proceed to patient 
registration in OPEN. 
 
4.3.1 OPEN / IWRS 
 
The Oncology Patient Enrollment Network (OPEN) is a web-based registration system available 
on a 24/7 basis.  OPEN is integrated with CTSU regulatory and roster data and with the LPOs 
registration/randomization systems or the Theradex Interactive Web Response System (IWRS) 
for retrieval of patient registration/randomization assignment.  OPEN or IWRS will populate the 
patient enrollment data in NCI’s clinical data management system, Medidata Rave. 
 
Requirements for OPEN access:   
 
• A valid CTEP-IAM account. 
• To perform enrollments or request slot reservations:  Must be on an LPO roster, ETCTN 
corresponding roster, or PO roster with the role of Registrar.  Registrars must hold a 
minimum of an Associate Plus (AP) registration type. 
• If a DTL is required for the study, the registrar must hold the OPEN Registrar task on the 
DTL for the site. 
• Have an approved site registration for the protocol prior to patient enrollment. 
 
To assign an Investigator (IVR) or Non-Physician Investigator (NPIVR) as the treating, 
crediting, consenting, drug shipment (IVR only), or receiving investigator for a patient transfer in 
OPEN, the IVR or NPIVR must list the IRB number used on the site’s IRB approval on their 
Form FDA 1572 in RCR.  If a DTL is required for the study, the IVR or NPIVR must be 
assigned the appropriate OPEN-related tasks on the DTL. 
 
Prior to accessing OPEN, site staff should verify the following: 
 
• Patient has met all eligibility criteria within the protocol stated timeframes, and  
• All patients have signed an appropriate consent form and Health Insurance Portability 
and Accountability Act (HIPAA) authorization form (if applicable). 
 
Note:  The OPEN system will provide the site with a printable confirmation of registration and 
treatment information.  IWRS system also sends an email confirmation of the registration.  You 
may print this confirmation for your records.  
 
Access OPEN at https://open.ctsu.org or from the OPEN link on the CTSU members’ website.  
Further instructional information is in the OPEN section of the CTSU website at 
https://www.ctsu.org or https://open.ctsu.org.  For any additional questions, contact the CTSU 
Help Desk at 1-888-823-5923 or ctsucontact@westat.com. 
 
Patient enrollment for this study will be facilitated using the Slot Reservation System in 

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conjunction with the registration system in OPEN.  Prior to discussing protocol entry with the 
patient, all site staff must use the CTSU OPEN Slot Reservation System or the IWRS Slot 
Reservation System to ensure that a slot on the protocol is available to the patient.  Once a slot 
reservation confirmation is obtained, site staff may then proceed to enroll the patient to this 
study.  
 
• Patients that have had a prescreening bone marrow biopsy will have a study slot reserved.  
o All prescreening clinical characteristics and cytogenetics from the bone marrow 
biopsy should be sent to the coordinating center for eligibility determination. 
 
4.3.2 Special Instructions for Patient Enrollment 
 
This Study will use the ETCTN Specimen Tracking System (STS).  
 
• All biospecimens collected for this trial must be submitted using the ETCTN Specimen 
Tracking System (STS) unless otherwise noted.   
• The system is accessed through Rave user roles:  “Rave CRA” and “Rave CRA 
(Labadmin)” for data entry at the treating institutions and “Biorepository” for users 
receiving the specimens for processing and storage at reference labs and the NCI Early-
Phase and Experimental Clinical Trials Biospecimen Bank (EET Biobank, formerly 
known as the ETCTN Biorepository).   
• Please refer to the Medidata Account Activation and Study Invitation Acceptance link on 
the CTSU website in the Data Management section under the Rave Home tab and then 
under Rave Resource Materials. 
• Important:  Failure to complete required fields in STS may result in a delay in 
sample processing.  Any case reimbursements associated with sample submissions will 
not be credited if samples requiring STS submission are not logged into STS. 
 
Detailed instructions on use of the STS can be found in Section 5.4. 
 
4.3.3 OPEN/IWRS Questions? 
 
Further instructional information on OPEN is provided on the OPEN link of the CTSU website 
at https://www.ctsu.org or at https://open.ctsu.org.  For any additional questions contact the 
CTSU Help Desk at 1-888-823-5923 or ctsucontact@westat.com.  
 
Theradex has developed a Slot Reservations and Cohort Management User Guide, which is 
available on the Theradex website:  http://www.theradex.com/clinicalTechnologies/?National-
Cancer-Institute-NCI-11. This link to the Theradex website is also on the CTSU website OPEN 
tab. For questions about the use of IWRS for slot reservations, contact the Theradex Helpdesk at 
609-619-7862 or Theradex main number 609-799-7580; CTMSSupport@theradex.com. 
 
4.4 
General Guidelines 
 
Following registration, patients should begin protocol treatment within 14 days.  Issues that 
would cause treatment delays should be discussed with the Principal Investigator.  If a patient 

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cold packs- please contact UNC TPF upon collection and shipment to alert for incoming 
samples.(unc_tpf@med.unc.edu). Do not send on Fridays. All specimens shipped to UNC 
TPF must contain appropriate labeling as outlined in section 5.4.2.1, and be accompanied 
by a shipping manifest. 
 
• Blood should be immediately ficolled to cryopreserve peripheral blood mononuclear cells 
for shipment on dry ice to the UNC Tissue Procurement Facility for storage upon request. 
If unable to ficoll, bone marrow should be shipped the day of collection using cold packs- 
please contact UNC TPF upon collection and shipment to alert for incoming samples. 
(unc_tpf@med.unc.edu). Do not send on Fridays. All specimens shipped to UNC TPF 
must contain appropriate labeling as outlined in section 5.4.2.1, and be accompanied by a 
shipping manifest. 
 
5.3.2.3 
Scheduling of Specimen Collections to the UNC-Molecular Genetic Laboratory. 
 
• Bone marrow should be shipped the day of collection when possible using cold packs.  
Do not send on Fridays. 
 
• Blood should be shipped the day of collection when possible with cold packs.  Do not 
send on Fridays. 
 
5.3.2.4 
Scheduling of Specimen Collections to Foundation Medicine 
 
• If procuring samples on Friday, please FedEx priority overnight and specify Saturday 
delivery on the shipping label to ensure timely receipt. 
 
5.3.2.5 
Scheduling of Specimen Collections to Hematologics 
 
• If shipping via FedEx for Saturday delivery, please use a Saturday delivery sticker (which 
Hematologics will provide) and check the Saturday delivery box on the address label.  
Both sticker and checked box are necessary to insure proper handling. 
 
5.4 
Specimen Tracking System Instructions 
 
5.4.1 Specimen Tracking System Overview and Enrollment Instructions 
 
For the ETCTN STS, the following information will be requested: 
• Protocol Number 
• Investigator Identification  
o Institution and affiliate name 
o Investigator’s name 
• Eligibility Verification:  Patients must meet all the eligibility requirements listed in 
Section 3. 
• Additional Requirements: 
o Patients must provide a signed and dated, written informed consent form. 
 

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Upon enrolling a patient, IWRS will communicate with OPEN, assigning two separate and 
unique identification numbers to the patient, a Universal patient ID (UPID) and a Treatment 
patient ID.  The UPID is associated with the patient and used each and every time the patient 
engages with the portion of this or any other protocol that uses the ETCTN Specimen Tracking 
System.  The UPID contains no information or link to the treatment protocol.  IWRS will 
maintain an association between the UPID for ETCTN biobanking and molecular 
characterization and any treatment protocols the patient participates in, thereby allowing analysis 
of the molecular characterization results with the clinical data.   
 
Immediately following enrollment, the institutional anatomical pathology report for the diagnosis 
under which the patient is being enrolled must be uploaded into Rave.  The report must include 
the surgical pathology ID (SPID), collection date, block number, and the IWRS-assigned UPID 
and patient study ID for this trial.  For newly acquired biopsies, the radiology and operative 
report(s) must also be uploaded into Rave.  Important:  Remove any personally identifying 
information, including, but not limited to, the patient’s name, date of birth, initials, medical 
record number, and patient contact information from the institutional pathology report 
prior to submission. 
 
Additionally, please note that the STS software creates pop-up windows when reports are 
generated, so you will need to enable pop-ups within your web browser while using the software.   
 
For questions regarding the Specimen Tracking System, please contact STS Support at 
STS.Support@theradex.com. 
 
The Shipping List report must be included with all sample submissions. 
 
5.4.2 Specimen Labeling 
 
 
5.4.2.1 Blood and Bone Marrow Specimen Labels 
 
 
Include the following on research-only bone marrow and blood specimens (including whole 
blood and frozen, processed blood products – like serum and plasma): 
• Patient Study ID 
• Universal Patient ID (UPID) 
• Specimen ID (automatically generated by Rave) 
• Time point 
• Specimen type (e.g., blood, serum, bone marrow) 
• Laterality, if applicable (bone marrow only) (to be added by hand) 
• Collection date (to be added by hand) 
• This does not apply to standard-of-care testing with Foundation One Heme Panel 
prior to treatment and Hematologics MRD.  
 
5.4.2.2 Example of Specimen Label Generated by STS 
 
STS includes a label printing facility, accessed via the Print Label CRF in the All Specimens 
folder.  A generated PDF is emailed to the user as a result of saving that form.  

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The following image is an example of a tissue specimen label printed on a label that is 0.5” high 
and 1.28” wide. 
 
 
  
 
The QR code in the above example is for the Specimen ID shown on the second line.   
 
Labels may be printed on a special purpose label printer, one label at a time, or on a standard 
laser printer, multiple labels per page.  Theradex recommends the use of these low temperature 
waterproof labels for standard laser printers: https://www.labtag.com/shop/product/cryo-laser-
labels-1-28-x-0-5-cl-23-colors-available/ 
 
The last line item on the label includes the following data points joined together: 
1. Tissue only: Primary (P), Metastatic (M), Normal (N) tissue indicated at the 
beginning of the specimen ID; this field is blank if not relevant (e.g., for blood) 
2. Block ID or blank if not relevant 
3. SPID (Surgical Pathology ID) or blank if none 
4. An optional alpha-numeric code that is protocol specific and is only included if the 
protocol requires an additional special code classification 
 
Space is provided at the bottom of the label for the handwritten date and optional time.  
The last line on the example label is for the handwritten date and optional time. 
 
5.4.3 Overview of Process at Treating Site 
 
5.4.3.1 OPEN Registration 
 
All registrations will be performed using the Oncology Patient Enrollment Network (OPEN) 
system.  OPEN communicates automatically with the Interactive Web Response System (IWRS) 
which handles identifier assignments, any study randomization, and any prescribed slot 
assignments.  If specimen analysis is required to determine eligibility, the protocol will be setup 
with multi-step registration. 
 
Registration with eligibility specimen analysis:  
 
1. Site enters first step data into OPEN. 

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2. IWRS receives data from OPEN, generates the Patient Study ID and the Universal Patient 
ID, both of which are sent back to OPEN. 
3. IWRS sends first step registration data, including the IDs and a TAC of “NOT REG” 
directly to Rave. 
4. The specimen tracking system in Rave is utilized for the specimen that contributes to 
eligibility determination. 
5. Site enters second and any subsequent step data into OPEN including results of specimen 
analysis. 
6. IWRS receives all data from OPEN, then sends it onto Rave with either the treatment 
TAC or a TAC of “SCRN FAIL”. 
7. In addition to the specimen tracking forms completed to determine eligibility, data entry 
for screen failure patients should include Histology and Disease, all forms in the Baseline 
folder, any lab forms connected to eligibility determination, and Off Treatment/Off 
Study. 
 
Any data entry errors made during enrollment should be corrected in Rave. 
 
5.4.3.2 Rave Specimen Tracking Process Steps 
 
Step 0: Log into Rave via your CTEP-IAM account, then navigate to the appropriate participant. 
 
Step 1:  Complete the Histology and Disease form (but do not upload reports until a specimen 
label can be applied to them) and the Baseline forms regarding Prior Therapies.  Enter the 
initial clinical specimen data:  
• Specimen Tracking Enrollment CRF:  Enter Time Point, Specimen Category, 
Specimen Type, Block number, Tissue type, Surgical Path ID, and number of labels 
needed (include extra labels to apply to reports to be uploaded).  CRF generates unique 
Specimen ID.  
 
Step 2:  Print labels using the Print Labels CRF located in the All Specimens folder, then 
collect specimen. 
• Label specimen containers and write collection date on each label.  After collection, store 
labeled specimens as described in Section 5.4.2. 
• Apply an extra specimen label to each report before scanning.  Return to the Histology 
and Disease form to upload any initial Pathology, Radiology, Bone Marrow, Molecular 
Reports (up to 4), and Surgical (or Operative) reports.  Return to Specimen Tracking 
Enrollment CRF to upload any molecular report (one per specimen) and/or specimen 
specific pathology or related report (one per specimen) and/or Tissue Biopsy Verification 
form (when applicable).  Uploaded reports should have protected health information 
(PHI) data, like name, date of birth, mailing address, medical record number or social 
security number (SSN), redacted.  Do not redact SPID, block number, diagnosis or 
relevant dates (such as collection date), and include the UPID and patient study ID on 
each document.  
 
Step 3:  Complete specimen data entry. 

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• Specimen Transmittal Form:  Enter collection date and time and other required 
specimen details. 
 
Step 4:  When ready to ship, enter shipment information. 
• Shipping Status CRF:  Enter tracking number, your contact information, recipient, 
number of sample containers and ship date once for the first specimen in a shipment. 
• Copy Shipping CRF:  In the specimen folders for additional specimens (if any) that will 
be shipped with the initial specimen, please use the Copy Shipping form to derive 
common data into additional Shipping Status forms. A few unique fields will still need 
to be entered in Shipping Status.   
Step 5:  Print shipping list report and prepare to ship.  
• Shipping List report is available at the site level. 
• Print two copies of the shipping list, one to provide in the box, the other for your own 
records. 
• Print pathology or other required reports to include in the box.  Be sure the printed copy 
includes the specimen label. 
 
Step 6:  Send email notification.  
• For only one of the specimens in the shipment, click “Send Email Alert” checkbox on the 
Shipping Status CRF to email recipient. 
 
Step 7:  Ship the specimen(s). 
 
Step 8: Monitor the Receiving Status form located in each specimen folder for acknowledgment 
of receipt and adequacy. 
 
5.5 
Specimen Collection  
 
5.5.1 Blood Collection  
 
5.5.1.1 Collection of Blood in Sodium Heparin Tubes for Shipping Whole Blood  
 
1. Peripheral blood samples will be obtained via phlebotomy. 
2. Label green-top vacutainer tubes according to the instructions in Section 5.4.2. 
3. Collect 10 mL blood in sodium heparin tube(s) and gently invert tube to mix. 
4. Ship on day of collection (whenever possible) according to instructions in Section 5.6. 
5. If blood cannot be shipped on the day of collection (e.g., a late scheduled collection), 
then refrigerate until shipment.  
 
5.5.1.2 Collection of Blood in EDTA for Shipping Whole Blood 
1. Peripheral blood samples will be obtained via phlebotomy. 
2. Label lavender-top vacutainer tubes according to the instructions in Section 5.4.2. 
3. Collect 10 mL blood in EDTA and gently invert tube to mix. 
4. Ship on day of collection (whenever possible) according to instructions in Section 5.6. 
5. If blood cannot be shipped on the day of collection (e.g., a late scheduled collection), 

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then refrigerate until shipment.  
 
5.5.2 Bone Marrow Collection  
 
5.5.2.1 
Collection of Bone Marrow aspirate in Sodium Heparin Tubes 
 
1. Bone marrow will be collected through standard access to iliac crest. 
2. Label green-top vacutainer tubes according to the instructions in Section 5.4.2. 
3. Aspirate bone marrow in 4-10 mL sodium heparin tube(s) and gently invert tube to mix. 
4. Ship on day of collection (whenever possible) according to instructions in Section 5.6. 
5. If bone marrow cannot be shipped on the day of collection (e.g., a late scheduled 
collection), then refrigerate until shipment.  
 
5.5.2.2 
Collection of Bone Marrow aspirate in EDTA tubes (for Foundation One HEME 
Collections) 
 
1. Bone marrow will be collected through standard access to iliac crest. 
2. Label green-top vacutainer tubes with clinical information. 
3. Aspirate bone marrow in 4-10 mL EDTA tube(s) and gently invert tube to mix. 
4. Ship on day of collection (whenever possible) according to instructions in Section 5.6. 
5. If bone marrow cannot be shipped on the day of collection (e.g., a late scheduled 
collection), then refrigerate until shipment.  
 
5.5.2.3 
Collection of Bone Marrow aspirate in EDTA tubes for DNA Sequencing 
 
1. Bone marrow will be collected through standard access to iliac crest. 
2. Label lavender-top vacutainer tubes according to the instructions in Section 5.4.2. 
3. Aspirate bone marrow in 4-10 mL EDTA tube(s) and gently invert tube to mix. 
4. Ship on day of collection (whenever possible) according to instructions in Section 5.6. 
5. If bone marrow cannot be shipped on the day of collection (e.g., a late scheduled 
collection), then refrigerate until shipment.  
 
5.5.2.4 
Collection of Bone Marrow aspirate in EDTA tubes for RNA Sequencing (TPF) 
 
1.   Bone marrow will be collected through standard access to iliac crest. 
2.   Label lavender-top vacutainer tubes according to the instructions in Section 5.4.2. 
3.   Aspirate bone marrow in 10 mL EDTA tube and gently invest tube to mix. 
4.   Immediately transfer the sample to a tissue processing facility that will separate the     
mononuclear cells over ficoll, cryopreserve, and store in liquid nitrogen until transfer to the 
UNC Tissue Procurement Facility in a dry ice shipment according to instruction in Section 
5.6. 
 
5.6 
Shipping of Specimens from Clinical Site to Other Laboratories  
 
5.6.1 Shipping of Specimens to Luznik Laboratory at JHU 
 

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5.6.1.1 
Specimen Shipping Instructions 
 
Ship stored samples after processing in batches. Please coordinate shipment with PI and Luznik 
Laboratory at JHU. If processing not able to occur per guidelines in Appendix M, please send 
fresh specimens overnight to the Luznik Laboratory at JHU. 
 
5.6.1.2 
Shipping Address 
Dr. Leo Luznik  
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center  
1650 Orleans St. 
Baltimore, MD 21287 
 
5.6.1.3 
Contact Information for Assistance 
Dr. Leo Luznik 
Leonido.luznik@bcm.edu 
5.6.2 Shipping of Specimens to Tissue Procurement Facility.  
 
5.6.2.1 
Specimen Shipping Instructions 
 
Ship cryopreserved peripheral blood mononuclear cell specimens on dry ice when requested by 
the PI/Project Manager. Ship overnight Monday-Thursday, excluding the day before a federal 
holiday. Several patients may be batched for shipment.  
 
Ship cryopreserved bone marrow mononuclear cell specimens on dry ice when requested by the 
PI/Project Manager.  Ship overnight Monday – Thursday, excluding the day before a federal 
holiday.  Several patients may be batched for shipment.   
 
5.6.2.2 
Shipping Address 
Tissue Procurement Facility 
108 MacNider Building, CB7304 
333 South Columbia St. 
Chapel Hill, NC 27599 
 
5.6.2.3 
Contact Information for Assistance 
Tissue Procurement Facility 
Phone: 919-966-2620 
unc_tpf@med.unc.edu 
 
5.6.3 Shipping of Specimens to UNC-Molecular Genetic Laboratory 
 
5.6.3.1 
Shipping specimen Instructions 
 
Ship fresh specimens overnight Monday-Thursday. Please send fresh samples. with 
cold packs. 
 

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5.6.3.2 
Shipping Address 
 
Molecular Genetics Lab 
McLendon Clinical Laboratories  
Outreach Services, 1st floor, East Wing  
UNC Hospitals  
Chapel Hill, NC - 27514  
 
5.6.3.3 
Contact Information for Assistance 
Rachana Kshatriya 
Phone: (984) 974-1825 
Rachana.Kshatriya@unchealth.unc.edu 
 
5.6.4 Shipping of Specimens to Foundation Medicine, Inc 
 
5.6.4.1 
Specimen Shipping Instructions 
 
See the following link for the most up to date instructions. 
https://assets.ctfassets.net/w98cd481qyp0/4qY3AxNKhJQF024FxoDmvU/cffb4094bc48e3badf1
25ccd5e43c645/FoundationOne_Heme_Specimen_Instructions__All_Sample_Types_.pdf 
 
The kits for Foundation Medicine are not supplied by the study. Please follow the instructions 
listed on the website above for sample collection. 
 
If procuring samples on Friday, please FedEx priority overnight and specify Saturday delivery on 
the shipping label to ensure timely receipt. 
 
5.6.4.2 
Shipping Address 
Foundation Medicine, Inc. 
7010 Kit Creek Road 
Morrisville, NC 27560 
 
5.6.4.3 
Contact Information for Assistance 
Phone: (888) 988-3639 
 
5.6.5 Shipping of Specimens to Hematologics 
 
Also see https://www.hematologics.com/shipping-instructions/hospital-shipping (cut and paste 
link in address bar) 
 
5.6.5.1 
Specimen Shipping Instructions 
 
1. Complete Requisition Attach Billing & Diagnostic Information. 
2. Seal Specimen in Biohazard Bag.  Place Specimen in Shipping Container and Close. 
3. Place Completed Requisition with Billing Information in Second Biohazard Bag & Seal. 
4. Place Iceberg Cool Pack on Top of Sealed Biohazard Bag and Close Shipping Container. 

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5. Place Shipping Container in FedEx Diagnostic Pack & Seal.  Complete and Attach 
Airbill.  If shipped on Friday, please mark for Saturday delivery and place Saturday 
delivery sticker on envelope. 
6. Call FedEx for Pick-Up (800-463-3339); Call Hematologics Client Services Dept. with 
Airbill Number (800-860-0934). 
 
5.6.5.2 
Shipping Address 
3161 Elliott Ave. Suite 200  
Seattle, WA 98121 
 
5.6.5.3 
Contact Information for Assistance 
Phone: (800) 860-0934 or (206) 223-2700 
FAX: (206) 223-5550 
 

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5.8 
Integrated Correlative Studies 
 
5.8.1 Foundation One Heme Panel  
 
5.8.1.1 
Specimen(s) Receipt and Processing at Foundation Medicine, Inc. 
 
Fresh bone marrow aspirate from pre-treatment should be sent to Foundation Medicine Inc. for 
NGS processing using the Foundation One Heme Panel.  Samples should be received one day 
after collection for optimal analysis.  Foundation One Heme Panel should be sent with clinical 
information and without study identification. 
 
If a patient has already had NGS performed at a CLIA-certified laboratory within 30 days of 
consent, then Foundation One Heme testing is not mandatory to be performed, per standard-of-
care and investigator discretion. 
 
See also: 
https://assets.ctfassets.net/w98cd481qyp0/4qY3AxNKhJQF024FxoDmvU/cffb4094bc48e3badf1
25ccd5e43c645/FoundationOne Heme Specimen Instructions
All Sample Types .pdf 
 
5.8.1.2 
Site Performing Correlative Study 
 
Foundation Medicine Inc. 
 
5.8.1.3 
Contact information for notification of specimen shipment 
 
Phone: (888) 988-3639 
 
5.8.2 Aiolos Expression 
 
5.8.2.1 
Specimen(s) Receipt and Processing at Luznik Laboratory at JHU 
 
Blood (sodium heparin tube) and bone marrow aspirate from pre-treatment, Day 14, Day 28 and 
at response will be shipped to the Luznik laboratory and processed according to laboratory SOPs 
for flow cytometry.  Briefly, at each sampling interval, bone marrow and peripheral blood 
mononuclear cells (PBMC) will be processed by Ficoll density gradient centrifugation.  Each 
sample is aliquoted in multiple vials of 10-15 x 106 cells/vial for bone marrow samples and 5-10 
x 106 cells/vial for PBMC. Specimen for Aiolos expression will be collected from UNC and JHU 
participants only. 
 
Frozen PBMCs will be transferred from the Luznik Lab at JHU to the Tissue Procurement 
Facility UNC-Chapel Hill for storage and then distributed to the Luznik Laboratory at Baylor 
College of Medicine for analysis. 
 
5.8.2.2 
Site Performing Correlative Study 
 

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Dr. Leo Luznik Laboratory; Baylor College of Medicine  
 
5.8.2.3 
Contact information for notification of specimen shipment 
 
Leo Luznik (Leonido.Luznik@bcm.edu)  
 
5.8.3 Hematologics Flow Cytometry Minimal Residual Disease  
 
5.8.3.1 
Specimen(s) Receipt and Processing at Hematologics 
 
Fresh bone marrow aspirate in sodium heparin green top tubes at pre-treatment and response will 
be sent to Hematologics for processing.  Hematologics MRD should be sent with clinical 
information and without study identification. 
 
5.8.3.2 
Site Performing Correlative Study 
 
Hematologics 
 
5.8.3.3 
Contact information for notification of specimen shipment 
 
Phone:  (800) 860-0934 or (206) 223-2700 
 
5.9 
Exploratory/Ancillary Correlative Studies 
 
5.9.1 T-Cell Subsets 
 
5.9.1.1 
Specimen(s) Receipt and Processing at Luznik Laboratory at JHU 
 
Bone marrow aspirates (collected pre-treatment, Day 14, Day 28 and at response) and blood 
(collected at pre-treatment, Day 21, Day 28, and at response) in sodium heparin tubes may be 
processed locally per guidelines in Appendix M or fresh samples sent to Dr. Luznik’s Laboratory 
(overnight).  The samples will be processed according to laboratory SOPs.  Briefly, at each 
sampling interval, bone marrow and PBMC will be processed by Ficoll density gradient 
centrifugation.  Each sample is aliquoted in multiple vials of 10-15 x 106 cells/vial for bone 
marrow samples and 5-10 x 106 cells/vial for PBMC. Specimen for Aiolos expression will be 
collected from UNC and JHU participants only. 
 
Frozen PBMCs will be transferred from Luznik Lab at JHU to the Tissue Procurement Facility 
UNC-Chapel Hill for storage and then distributed to the Luznik Laboratory at Baylor College of 
Medicine for analysis. 
 
 
5.9.1.2 
Site Performing Correlative Study 
 
Dr. Leo Luznik Laboratory; Baylor College of Medicine  
 

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5.9.1.3 
Contact information for notification of specimen shipment 
 
Leo Luznik (Leonido.Luznik@bcm.edu) 
 
5.9.2 DNA-Seq 
5.9.2.1 
Specimen(s) Receipt and Processing at  Molecular Genetics Laboratory 
Bone marrow aspirate and peripheral blood pre-treatment and at response will be shipped to 
University of North Carolina Molecular Genetics Laboratory overnight for processing and 
storage. DNA-Sequencing will be done at a later date to assess for MRD.  
 
5.9.3 RNA-Seq and TCR Diversity 
 
5.9.3.1 
Specimen(s) Receipt and Processing at the Tissue Procurement Facility UNC-Chapel 
Hill. 
 
Peripheral blood samples (10 ml EDTA x 2 or 8 ml ACD x 3) from Pre-Treatment, Day 21 (For 
Arm A should be before pomalidomide) and Response between days 42 and 64 will be processed 
locally if possible according to the laboratory SOPs to process by Ficoll density gradient 
centrifugation and cryopreserve in multiple vials of 5-10 x 106 cells/vial for PBMC. Multiple 
cryopreserved patient samples may be batched for overnight shipment on dry ice to the Tissue 
Procurement Facility UNC-Chapel Hill upon request. 
 
5.9.3.2 
Site Performing Correlative Study 
RNA-Seq: Tissue Procurement Facility UNC-Chapel Hill (DNA-seq: TBD) 
 
Bone marrow aspirates (collected pre-treatment and Response (between Days 42 and 64) in 
EDTA tubes should be processed locally according to prepare Bone Marrow Mononuclear Cells 
(BMMC) following ficol hypaque gradient centrifugation and cryopreservation in multiple vials 
that must exceed 5 x 106 cells/vial.   After cryopreservation protocols are completed, samples 
must be stored under liquid nitrogen vapor phase until transfer to UNC Chapel Hill.  Multiple 
patient samples may be batched for shipment overnight on dry ice to the Tissue Procurement 
Facility UNC-Chapel Hill. 
 
5.9.3.3 
Contact information for notification of specimen shipment 
TPF Lab (unc_tpf@med.unc.edu) 
 
6. 
TREATMENT PLAN 
  
 
6.1 
Agent Administration 
 
Treatment will be administered on an inpatient or outpatient basis based on institutional standard 
until Day 6, and then all patients will be hospitalized starting on Day 6 of therapy until early 
hematologic recovery.  Patients can be discharged once they achieve early hematologic recovery 
or per institutional standards.  Reported adverse events and potential risks are described in 
Section 10.  Appropriate dose modifications are described in Section 7.  No investigational or 
commercial agents or therapies other than those described below may be administered with the 

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intent to treat the patient's malignancy.  To prevent hyperuricemia, all patients without known 
allergy will receive allopurinol 300 mg PO QD prior to beginning chemotherapy continuing 
through the period of maximal tumor lysis (at least through Day 5) or other antiuricemia regimen 
per institutional practice (refer to Section 6.2.6).   
 
6.2 
Safety Run-in 
A safety run-in will be performed for pomalidomide dose finding purposes utilizing a standard 3 
+ 3 design. After daunorubicin and cytarabine liposome induction, up to 12 subjects will enter 
the safety run-in phase. There will be two dose levels (DLs). The dose for each dose level will 
remain the same (4 mg), while the duration of pomalidomide exposure will vary from 14 days to 
21 days.   
 
Pomalidomide Safety Run-in Dose Levels 
Dose Level 
Dose (mg) 
Duration (Days) 
-1 
4 
10 
1 
4 
14 
2 
4 
21 
 
6.3 
Dose Escalation 3 + 3 Design 
The safety run-in will follow a traditional 3 + 3 design. Three (3) subjects will be evaluated at 
each dose level for treatment-emergent toxicities.  The maximum tolerated dose (MTD) will be 
defined as the highest dose tested in which more than 2 dose limiting toxicity (DLT; Section 6.4) 
occurred in evaluable subjects at that dose level using the following escalation procedure: 
•  If none of the first 3 subjects on DL1 experience a DLT, the dose may be escalated to the 
next level 
• If 1 of the first 3 subjects on any DL experiences a DLT, then 3 additional subjects will 
be studied at the same dose level. If 1 or more of these 3 new subjects experience a DLT, 
then the MTD has been exceeded. 
• If ≥ 2 subjects in a cohort of 3 experience a DLT, 3 additional subjects will be assigned to 
the lower dose level unless there have been 6 subjects already at that dose level, or this 
occurs in DL1.  If needed, a dose level minus 1 incorporating 4 mg pomalidomide for 10 
days will be employed. 
The recommended phase 2 dose (RP2D) to be used in the randomized phase 2 portion of the 
study will be determined after evaluating safety, tolerability, efficacy, anti-tumor activity, 
exposure, and PD information (ie, Aiolos inhibition), if available, for both dose levels. 
Additionally, the RP2D will not exceed the estimated MTD and will be no greater than DL2.  
 
6.4 
Definition of a Dose Limiting Toxicity 
DLTs related to pomalidomide will be graded per CTCAE v5.0 and be defined as the following:  
Grade ≥3 non-hematologic toxicity at least possibly related to pomalidomide and not related to 
underlying leukemia with the following exceptions: 
 
A) Grade ≥3 isolated electrolyte abnormalities that last <72 hours with or without supportive 
care 

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B) Grade 3 anorexia, nausea, vomiting or diarrhea if it does not result in hospitalization or 
prolongation of hospitalization or parenteral nutrition via tube-feeds or central/total 
parenteral nutrition.  
C) Infection, bleeding, or other direct complication of cytopenias due to underlying leukemia 
D) Grade >3 tumor lysis syndrome if successfully managed clinically and resolving with 7 
days without end-organ damage. 
Furthermore, the following will be considered as DLTs if they are determined to be at least 
possibly related to treatment regimen: 
• Grade 2 elevation of AST or ALT (>3x upper limit normal) and elevation of total 
bilirubin 2x upper limit normal without other known causes such as cholestasis 
• Non-hematologic grade ≥ 4 toxicity (excluding infection)   
Hematologic toxicity will be considered as a DLT if grade 4 neutropenia (ANC < 0.5x 109/L) 
and grade 4 thrombocytopenia (platelets < 25 x 109/L or transfusion-dependent) occur without 
evidence of persistent leukemia (i.e. <5% blasts in bone marrow) after >49 days from start of 
induction or re-induction for those receiving 1 or 2 induction cycles, respectively.  This will 
apply until receipt of subsequent therapy but no more than 30 days after response assessment for 
each individual patient. 
 
6.5 
Randomization Phase 
Randomization will occur prior to initiation of daunorubicin and cytarabine liposome and will be 
stratified by the following: 
1) Age ≥60 vs. <60 years of age 
2) Newly diagnosed AML with preexisting MDS, CMML, or MPN (or unexplained 
cytopenias >6 months) vs. 2) therapy-related AML vs. 3) AML with MRC based on 
cytogenetics or morphologic dysplasia without history of MDS/MPN. 
 
Regimen Description 
Agent 
Premedications; 
Precautions 
Dose 
Route 
Schedule 
Cycle 
Length
- up to 
64 (+/- 
3 days) 
daunorubicin 
and cytarabine 
liposome 
(Arm A  
and Arm B) 
In response to 
hypersensitivity 
reactions (See 
Section 7.2), 
antihistamines 
and/or 
corticosteroids 
may be 
administered. 
See Section 6.2 
Induction and 
second induction 
(if required): 
Daunorubicin  
44 mg/m2 and 
cytarabine 
100mg/m2 
 
Consolidation: 
For patients who 
IV over 
90 
minutes 
(+/- 15 
minutes) 
Induction: 
Days 1, 3, and 5 
during induction. 
 
Second 
induction (if 
required): 
Days 1 and 3 on 
the subsequent 
induction cycle. 
Inductio
n = 42+ 
days 
 
 
 
Consoli
dation = 
5-8 
weeks 

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and 11 for 
additional 
premedications/pr
ecautions. 
achieve CR/CRi, 
daunorubicin  
29 mg/m2 and 
cytarabine  
65 mg/m2 
 
 
Consolidation: 
Days 1 and 3 for 
up to 2 cycles. 
Should start 5-8 
weeks after the 
start of 
induction.  If a 
second 
consolidation 
cycle is 
administered, it 
should be 5-8 
weeks after the 
start of the first 
consolidation. 
cycle  
Pomalidomide 
(Arm A only) 
 
4 mg 
PO 
Daily after 
induction, 
beginning Day 
21 (+3 days) for 
one cycle for 
Arm A only 
14 days 
(as 
determi
ned in 
the run-
in 
phase) 
 
Arm A:  
For induction, daunorubicin and cytarabine liposome (liposomal daunorubicin 44 mg/m2 and 
cytarabine 100 mg/m2) is administered IV Days 1, 3 and 5.  If patients require a second 
induction, they will receive daunorubicin and cytarabine liposome (liposomal daunorubicin 44 
mg/m2 and cytarabine 100 mg/m2) IV on Days 1 and 3. Daunorubicin and cytarabine liposome 
consolidation (liposomal daunorubicin 29 mg/m2 and cytarabine 65 mg/m2) will occur >24 hours 
after completing pomalidomide and after achievement of CR/CRi.  
 
Pomalidomide 4 mg daily is given for 14 days starting on Day 21 after induction or at least 48 
hours after second induction has been completed, but may be delayed until Day 30.  Patients may 
be discharged from the hospital once they achieve early hematologic recovery (i.e., ANC ≥0.5 x 
109/L and platelets >50 x 109/L) or per institutional standards. 
 
All patients will be assessed for laboratory eligibility and patients in Arm A need to meet 
laboratory eligibility parameters in Criterion 3.1.6 prior to initiating pomalidomide.  
Pomalidomide initiation can be delayed (up to Day 30) in the following scenarios: 
• Patients who receive re-induction with daunorubicin and cytarabine liposome 
(pomalidomide must be initiated no sooner than 48 hours after last dose of daunorubicin 
and cytarabine liposome) 
• Patients who do not meet laboratory eligibility criteria on Day 21 but correct to eligibility 
criteria with supportive care by Day 30 

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• Patients with intercurrent illness whereby the investigator deems it unsafe to administer 
pomalidomide 
 
Arm B:  
Daunorubicin and cytarabine liposome (liposomal daunorubicin 44 mg/m2 and cytarabine 100 
mg/m2) is administered IV Days 1, 3 and 5.  If patients require a second induction, they will 
receive daunorubicin and cytarabine liposome (liposomal daunorubicin 44 mg/m2 and cytarabine 
100 mg/m2) IV on Days 1 and 3.  
 
Arm A and B Consolidation: 
Patients in both arms who achieve CR/CRi will receive consolidation therapy with daunorubicin 
and cytarabine liposome (29 mg/m2 daunorubicin and 65 mg/m2 cytarabine) IV infusion on Days 
1 and 3 per standard-of-care for up to 2 cycles.  In patients who develop cardiomyopathy or who 
exceed lifetime anthracycline dose of >430 mg/m2 (or >280 mg/m2 with prior mediastinal 
radiation) or have any other contraindications to daunorubicin and cytarabine liposome 
consolidation, moderate- to high-dose (1-3 g/m2 IV Q12 hours Days 1, 3, and 5) cytarabine 
should be used in place of daunorubicin and cytarabine liposome for consolidation (See 
Appendix I).  An allogeneic stem cell transplant will be performed for patients who are 
candidates for a transplant per investigator discretion in either arm after induction therapy, before 
or after consolidation therapy. 
 
6.5.1 Pomalidomide 
• Pomalidomide is administered by mouth (orally) without regards to food or other oral 
intake. 
• Pomalidomide capsules should be swallowed whole, and should not be broken, chewed, 
or opened. 
• If a dose of pomalidomide is missed, the dose may still be taken up to 12 hours after the 
time they normally would take it.  If more than 12 hours have elapsed, the dose should be 
skipped.  Take the next dose at the usual time.  Patients should not take 2 doses to make 
up for the one they missed. 
• If a patient vomits after taking pomalidomide, doses will not be made up and should be 
taken at the next scheduled dose. 
• Patients who take more than the prescribed dose of pomalidomide should be instructed to 
seek emergency medical care if needed and contact study staff immediately.  
 
Treatment compliance 
At all times, when dispensing study drug, research center personnel will review the instructions, 
printed on the packaging, with patients.  Patients will be asked to maintain a diary to record the 
drug administration (see Appendix H).  Patients will be asked to bring any unused study drug 
and empty study drug containers to the research center at their next visit.  Research personnel 
will count and record the number of used and unused study drug capsules at each visit and 
reconcile with the patient diary.  
 
6.5.2 Daunorubicin and cytarabine liposome 
 

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Daunorubicin and cytarabine liposome is a sterile, preservative-free, purple, lyophilized cake 
for reconstitution supplied in a single-dose clear glass vial as follows: 
• For injection: 44 mg daunorubicin and 100 mg cytarabine in a 1:5 molar ratio 
encapsulated in liposomes for intravenous administration.  
 
The use of daunorubicin and cytarabine liposome is contraindicated in patients with the 
following:  
• History of serious hypersensitivity reaction to cytarabine, daunorubicin, or any 
component of the formulation 
Please clarify or add a reference to section 6.1 about consolidation and allowed use of moderate 
to high dose cytarabine to replace daunorubicin and cytarabine liposome during consolidation. 
 
Do not interchange with other daunorubicin-and/or cytarabine-containing products  
Due to substantial differences in the pharmacokinetic parameters, the dose and schedule 
recommendations for daunorubicin and cytarabine liposome are different from those for 
daunorubicin hydrochloride injection, cytarabine injection, daunorubicin citrate liposome 
injection, and cytarabine liposome injection.  Verify drug name and dose prior to preparation 
and administration to avoid dosing errors.  Do not substitute other preparations of daunorubicin 
or cytarabine for daunorubicin and cytarabine liposome.  Moderate- to high-dose (1-3 g/m2 IV 
Q12 hours Days 1, 3, and 5) cytarabine can be used in place of daunorubicin and cytarabine 
liposome for consolidation (See Section 6.1, Arm A and B Consolidation). 
 
6.6 
General Concomitant Medication and Supportive Care Guidelines 
 
Patients should receive full supportive care, including transfusions of blood and blood products, 
antibiotics, and antiemetics when appropriate.  
 
Because there is a potential for interaction of pomalidomide with other concomitantly 
administered drugs, the case report form must capture the concurrent use of all other drugs, over-
the-counter medications, or alternative therapies.  The Principal Investigator should be alerted if 
the patient is taking any agent known to affect or with the potential for drug interactions.  The 
study team should check a frequently-updated medical reference for a list of drugs to avoid or 
minimize use of.  Appendix C (Patient Clinical Trial Wallet Card) should be provided to 
patients. 
 
Pomalidomide is primarily metabolized by CYP1A2 and CYP3A4 and is a substrate for P-gp.  
Caution should be used with concomitant strong CYP1A2 inhibitors and alternative agents 
should be used if possible.  
 
6.6.1 Antiemetics 
 
Antiemetics will be used according to standard practices.  Any 5-hydroxytryptamine (5-HT3) 
receptor inhibitor (e.g. ondansetron) combined with haloperidol or prochlorperazine as needed, 
will be used during chemotherapy infusions and during pomalidomide administration, as needed.  
A typical antiemetic regimen prior to daunorubicin and cytarabine liposome may be the 
following:  

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• Zofran 24 mg PO and dexamethasone 8 mg PO on D1, 3, and 5 administered 30 min 
prior to dose. 
 
6.6.2 Menstrual Suppression 
 
During the period of thrombocytopenia, to reduce the risk of bleeding, all premenopausal women 
should receive menstrual suppression.  All premenopausal women who are in the pre-ovulatory 
half of the menstrual cycle will be placed on daily combination (estrogen + progesterone) oral 
contraceptive pills.  All premenopausal women who are in the post-ovulatory phase (>14 days 
from last menstrual period) of the menstrual cycle will be given megestrol 40 mg QD x 2 days or 
institutional equivalent and then begun on combination oral contraceptive pills beginning 5 days 
after the onset of withdrawal bleeding.  Combination pills will be continued throughout drug-
induced aplasia if breakthrough bleeding does not occur.  Breakthrough bleeding will be 
managed by increasing the progesterone content of the combination pills until bleeding is 
controlled.  This increase can be achieved by doubling the dose of combination oral 
contraceptive.  If bleeding is not controlled by 2 combination pills QD, a trial of megestrol (40-
80 mg QD or equivalent) is indicated.  Oral contraceptives or megestrol could be stopped after 
marrow recovery and achievement of platelet count of at least 30 x 109/L in order to permit 
endometrial sloughing unless used for ongoing pregnancy protection while taking pomalidomide.  
Similar menstrual suppression guidelines per institutional standard may be followed. 
 
6.6.3 Antimicrobial Prophylaxis 
 
Patients should receive prophylaxis directed against gram-negative gastrointestinal infections 
(GI), candidiasis, and/or herpes simplex virus (HSV), according to institutional standards. 
 
6.6.4 Intrathecal prophylaxis 
 
Intrathecal prophylaxis will be used according to institutional standard practice for those patients 
presenting with elevated WBCs.  Any patient presenting with WBC >40 x 109/L or any 
monocytic phenotype should have screening lumbar puncture after clearance of peripheral blood 
blasts preferably by Day 14 of induction chemotherapy with prophylactic intrathecal 
chemotherapy instillation of cytarabine per institutional standards.  Patients receiving intrathecal 
chemotherapy prophylaxis should not start pomalidomide for ≥3 days after chemotherapy 
administration.  
 
6.6.5 Colony Stimulating Factors and Steroids 
 
The routine use of colony stimulating factors is disallowed only during induction (e.g., this does 
not refer to consolidation).  The use of colony stimulating factors in the presence of severe 
infection should be discussed with the study chair before implementation.  Fever and rash are 
common side effects of pomalidomide.  Low dose steroids (up to max 40 mg of prednisone per 
day or equivalent steroid dose) may be used as needed to control symptoms as long as infectious 
cause for fever has been excluded.  This should be discussed with the study chair before 
implementation. 
 

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6.6.6 Management of Tumor Lysis Syndrome (TLS) 
 
Tumor lysis occurs as part of initial cytoreductive therapy.  The most extreme form, TLS, is 
characterized by hyperuricemia, hyperphosphatemia, increased lactate dehydrogenase (LDH) 
coagulopathy, and a potential cytokine release syndrome.  Since the occurrence of TLS is 
magnified in the presence of high leukemia burden, we will not begin induction chemotherapy in 
any patient whose blood blast count is >30 x 109/L (see Eligibility 3.2.2).  TLS also occurs with 
higher propensity in monoblastic phenotypes. 
 
Tumor lysis labs consisting of basic metabolic panel, uric acid, LDH, and phosphate, must be 
drawn a minimum of twice daily at least through Day 5 of chemotherapy. Tumor lysis labs 
should be performed if clinically indicated after day 5 until maximum tumor lysis has abated.  
The following precautionary and prophylaxis regimens are suggested prior to and during initial 
chemotherapy administration: 
• To prevent hyperuricemia, all patients without known allergy will receive allopurinol 300 
mg PO QD prior to beginning chemotherapy and continuing through the period of 
maximal tumor lysis (at least through Day 5) or other antiuricemia regimen per 
institutional practice.  Rasburicase may be used per institutional policy for 
hyperuricemia. Screening for G6PD deficiency should be obtained in susceptible 
populations before beginning Rasburicase. 
• If there is an evidence of hyperphosphatemia prior or during administration of 
daunorubicin and cytarabine liposome, an oral phosphate binder per institutional practice 
(i.e., sevelamer 400-800 mg) should be administered orally every 8 hours and continued 
as tolerated until hyperphosphatemia is resolved. 
• Cytokine release syndrome can occur shortly after completion of drug infusion, 
accompany severe TLS, or after pomalidomide and present with fever, bronchospasm 
with dyspnea and/or respiratory distress, altered blood pressure, myalgias, arthralgias, 
tumor pain and/or urticarial rash.  Any patient with cytokine release syndrome should 
receive 20 mg dexamethasone (or equivalent steroid) IV immediately. 
 
6.6.7 Anticoagulation Consideration 
 
Pomalidomide may increase the risk of thrombotic events in patients who are at high risk or with 
a history a thrombosis, in particular when combined with other drugs known to cause 
thrombosis.  Anticoagulation is not necessary while on pomalidomide unless patients have a 
high-risk for thrombosis (i.e. prior history).  Consideration should be given to the optional use of 
aspirin (81 or 325 mg) in patients with a high-risk of thrombosis while on pomalidomide and 
with platelet count >30 x 109/L.  Low molecular weight heparin may be utilized in patients that 
are intolerant to ASA.  Routine use of warfarin is discouraged.  Patients with AML will be 
allowed to start prophylactic antithrombotic therapy (if deemed high-risk) only when their 
platelet count is stable and >30 x 109/L unless they need therapeutic anticoagulation. 
 
6.7 
Duration of Therapy 
 
In the absence of treatment delays due to adverse event(s), treatment may continue for up to two 
consolidation cycles of daunorubicin and cytarabine liposome or until one of the following 

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criteria applies: 
 
• 
Disease progression or relapse 
 
• 
Intercurrent illness that prevents further administration of treatment 
 
• 
Unacceptable adverse event(s) 
 
• 
Patient decides to withdraw from the study 
 
• 
General or specific changes in the patient's condition render the patient unacceptable for 
further treatment in the judgment of the investigator 
 
• 
Patient non-compliance 
 
• 
Pregnancy 
 
o All women of childbearing potential should be instructed to contact the investigator 
immediately if they suspect they might be pregnant (e.g., missed or late menstrual 
period) at any time during study participation. 
 
o The investigator must immediately notify CTEP in the event of a confirmed 
pregnancy in a patient participating in the study. 
 
• 
Termination of the study by sponsor 
 
• 
The drug manufacturer can no longer provide the study agent 
 
• 
Patients have treatment delays >2 weeks 
 
The reason(s) for protocol therapy discontinuation, the reason(s) for study removal, and the 
corresponding dates must be documented in the Case Report Form (CRF). 
 
6.8 
Duration of Follow-Up 
 
Patients will be followed for 5 years after the start of induction therapy or until death, whichever 
occurs first.  Patients removed from study for unacceptable adverse event(s) will be followed 
until resolution or stabilization of the adverse event. 
 
In patients who complete consolidation chemotherapy and do not undergo an allogeneic stem 
cell transplant, patients should be followed approximately once every 1-2 months for the first 
year per institutional standard-of-care.  Additionally, patients should receive surveillance bone 
marrow aspirate and biopsy while in remission approximately every 3 months for the first year 
after completing daunorubicin and cytarabine liposome consolidation.  
 

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7. 
DOSING DELAYS/DOSE MODIFICATIONS 
 
7.1 
Pomalidomide 
 
Toxicities are graded using CTCAE v5.0.  Grade ≥3 non-hematologic toxicities that are 
determined to be at least possibly related to pomalidomide and not related to underlying 
leukemia will require pomalidomide to be held until grade <1 and then restarted at 2 mg daily for 
the remainder of their treatment cycle (see Table below) with the following exceptions: 
A) Grade >3 isolated electrolyte abnormalities that last <72 hours with or without supportive 
care 
B) Grade 3 anorexia, nausea, vomiting or diarrhea if it does not result in hospitalization or 
parenteral nutrition via tube-feeds or central/total parenteral nutrition.  
C) Infection, bleeding, or other direct complication of cytopenias due to underlying leukemia 
D) Grade >3 tumor lysis syndrome if successfully managed clinically and resolving with 7 
days without end-organ damage. 
Additionally, subjects who develop grade 2 elevation of AST or ALT (>3x upper limit normal) 
and elevation of total bilirubin 2x upper limit normal without other known causes such as 
cholestasis will require pomalidomide to be held until improvement of AST/ALT and total 
bilirubin. Pomalidomide should be restarted at 2 mg daily after clinical improvement of these 
laboratory parameters.  
Pomalidomide should be held if grade 4 neutropenia or thrombocytopenia occurs lasting >49 
days from start of induction or reinduction in absence of active AML. 
Pomalidomide should be held for grade 4 infectious toxicities and restarted at 2 mg daily once 
infection-related toxicity is <grade 3.   
Missed doses of pomalidomide not taken within 12 hours of the time normally taken will not be 
made up.  Patients with grade ≥3 maculopapular rash on pomalidomide should have drug held 
until improvement to ≤ grade 2.  Patients who have symptoms and/or clinical sequelae of rash 
can receive concomitant prednisone and supportive care while remaining on pomalidomide.  
Patients with Stevens-Johnson Syndrome (SJS) or toxic epidermal necrolysis (TEN) should be 
taken permanently off pomalidomide.  If tumor lysis syndrome develops on pomalidomide, 
subsequent doses should be held until tumor lysis syndrome resolves.  Hematologic toxicity may 
occur after pomalidomide administration.  Dose modifications will not occur during 
pomalidomide administration for hematologic toxicities.  
Grade ≥3 venous or arterial thromboses will require pomalidomide to be discontinued 
permanently and subjects should be treated off study.  
Subjects experiencing angioedema, skin exfoliation or any other severe dermatologic reaction 
should permanently discontinue pomalidomide and be treated off study.  
 
For patients with mild or moderate hepatic impairment (Child-Pugh A or B), reduce the 
recommended dosage to 3 mg orally daily. 
 

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For patients with severe hepatic impairment (Child-Pugh C), reduce the recommended dosage to 
2 mg. 
 
Other Non-
Hematologic 
Toxicity  
(with the exception 
of toxicities listed 
above) 
Management/Next Dose for Pomalidomide 
≤ Grade 1 
No change in dose 
Grade 2 
No change in dose 
Grade 3 or 4 
Hold* until grade ≤1, and then restart at 2 mg.  If grade 3 or 4 event 
occurs on lower dose (2 mg), then permanently discontinue 
pomalidomide.  Missed doses should not be made up.  
*Patients requiring a delay of >2 weeks should go off protocol therapy. 
 
Thromboembolic Events 
Management/Next Dose for Pomalidomide 
≤ Grade 2 
No change in dose 
Grade >3 
Start anticoagulation as per standard-of-care. Pomalidomide 
should be discontinued.  
 
Strong CYP1A2 Inhibitors 
The use of strong CYP1A2 inhibitors (e.g. ciprofloxacin, fluvoxamine) should be avoided or 
used with caution.  If a strong CYP1A2 inhibitor must be used, reduce the pomalidomide dose by 
50%.  
 
7.2 
Daunorubicin and cytarabine liposome 
 
Missed Doses of daunorubicin and cytarabine liposome  
If a planned dose of daunorubicin and cytarabine liposome is missed, administer the dose as soon 
as possible and adjust the dosing schedule accordingly, maintaining the treatment interval.  
 
Hypersensitivity Reactions  
For hypersensitivity reactions of any grade/severity, interrupt daunorubicin and cytarabine 
liposome infusion immediately and manage symptoms.  Reduce the rate of infusion or 
discontinue treatment as outlined below:  
• Mild symptoms:  Once symptoms resolve, reinitiate infusion at half the prior rate of 
infusion.  Consider premedication with antihistamines and/or corticosteroids for 
subsequent doses of daunorubicin and cytarabine liposome.  
• Moderate symptoms:  Do not reinitiate infusion.  For subsequent doses of daunorubicin 
and cytarabine liposome, premedicate with antihistamines and/or corticosteroids prior to 
initiating infusion at same rate.  
• Severe/life-threatening symptoms:  Permanently discontinue daunorubicin and cytarabine 
liposome treatment, treat according to the standard-of-care to manage symptoms, and 
monitor patient until symptoms resolve.  
 

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Pomalidomide capsules are supplied in high density polyethylene (HDPE) containers fitted 
with induction seals and child-resistant plastic closures. Each bottle contains 100 capsules. 
 
Storage: Store at 20°C-25°C (68°F-77°F) [USP Controlled Room Temperature] 
 
If a storage temperature excursion is identified, promptly return pomalidomide to 
controlled room temperature and quarantine the supplies. Provide a detailed report of the 
excursion (including documentation of temperature monitoring and duration of the 
excursion) to PMBAfterHours@mail.nih.gov for determination of suitability. 
 
Stability: Shelf life studies are ongoing for investigational supplies. Refer to the package labeling 
for commercially-labeled supplies. 
 
Route of Administration: Take by mouth with or without food. Capsules should be swallowed 
whole and taken with water and not crushed, chewed or opened. If patients miss a dose, the 
dose may still be taken up to 12 hours after the time they normally would take it.  If more than 
12 hours have elapsed, the dose should be skipped. Take the next dose at the usual time. 
Patients should not take 2 doses to make up for the one they missed. 
 
Dispensing: Dispense one cycle or up to a 28-day supply (whichever is shorter) at one time. Sites 
may not mail pomalidomide to patients. 
 
Patient Care Implications and Counseling: 
  
Risks Associated with Pregnancy 
Pomalidomide is structurally related to thalidomide. Thalidomide is a known human 
teratogenic active substance that causes severe life-threatening birth defects. An 
embryofetal development study in animals indicates that pomalidomide produced 
malformations in the offspring of female monkeys who received the drug during 
pregnancy. The teratogenic effect of pomalidomide in humans cannot be ruled out. 
Therefore, a risk minimization plan to prevent pregnancy must be observed. 
 
Definition of female of childbearing potential (FCBP) 
This protocol defines a female of childbearing potential 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 (i.e., has had 
menses at any time in the preceding 24 consecutive months). 
 
Before starting study drug: 
 
Female Subjects:   
• FCBP must have two negative pregnancy tests (minimum sensitivity of 25 mIU/mL) 
prior to starting study drug. The first pregnancy test must be performed within 10-14 days 
prior to the start of study drug and the second pregnancy test must be performed within 

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24 hours prior to the start of study drug. The subject may not receive study drug until the 
Investigator has verified that the results of these pregnancy tests are negative.  
• FCBP must agree to use two reliable forms of contraception simultaneously, or practice 
complete abstinence for 28 days before starting pomalidomide, while taking 
pomalidomide, during dose interruptions, and for at least 28 days after the last dose of 
pomalidomide. 
 
Male Subjects:   
• Must agree to use a latex condom during sexual contact with females of childbearing 
potential while participating in the study, during dose interruptions, and for at least 28 
days following discontinuation from the study even if he has undergone a successful 
vasectomy.  
 
All Subjects: 
• Only enough pomalidomide for one cycle of therapy may be dispensed with each cycle of 
therapy.  
 
• If pregnancy or a positive pregnancy test does occur in a study subject or the partner of a 
male study subject during study participation, pomalidomide must be immediately 
discontinued. 
 
Counseling 
• In investigational studies where pomalidomide is supplied by the NCI, patients will be 
counseled by a qualified healthcare professional (including but not limited to, nurses, 
pharmacists and physicians). Two healthcare professionals at each site will be trained by 
Celgene in requirements specific to counseling of subjects (investigators cannot counsel 
patients as part of this requirement). Refer to specific protocol sections for more 
information about training requirements. 
 
• Once trained, these healthcare staff will counsel subjects prior to medication being 
dispensed to ensure that the subject has complied with all requirements including use of 
birth control and pregnancy testing (FCBP) and that the subject understands the risks 
associated with pomalidomide. This step will be documented with a completed 
Pomalidomide Education and Counseling Guidance Document (Appendix E) and no drug 
will be dispensed until this step occurs. Counseling includes verification with the patient 
that required pregnancy testing was performed and results were negative. A 
Pomalidomide Information Sheet (Appendix F) will be supplied with each medication 
dispense. 
 
 
Potential Drug Interactions:   
Pomalidomide is metabolized mostly by CYP 1A2 and 3A and is substrate for P-
glycoprotein (P-gp). In vitro studies showed a significant plasma increase when strong CYP 
1A2, 3A and P-gp inhibitors were given simultaneously.  Avoid concomitant administration 
of strong inducers and inhibitors of CYP 1A2, 3A and P-gp in patients receiving 

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pomalidomide. Closely monitor INR when patients receive concomitant warfarin and 
dexamethasone. Refer to the protocol for pomalidomide dose modifications.  
 
Pomalidomide does not inhibit CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, or 3A4/5 in 
vitro.  It is also not an inhibitor of P-gp, BCRP, OATP1B1, OATP1B3, OAT1, OAT3, or 
OCT2. 
 
Pomalidomide does not induce CYP1A2, 2B6, 2C9, 2C19, or 3A4/5 in vitro. 
 
Special Handling:  
Pomalidomide should not be handled by non-patient FCBP or non-patient partners of 
FCBP unless gloves are worn. If any contact with a broken pomalidomide capsule or the 
medicine in the capsule occurs, the exposed area should be washed immediately and 
thoroughly with soap and water. 
 
Patient Care Implications: 
 
Patients should be advised that smoking tobacco may reduce the efficacy of pomalidomide. 
 
 
Pomalidomide can be removed by hemodialysis. 
 
 
8.1.2 Availability 
 
Pomalidomide is an investigational agent supplied to investigators by the Division of Cancer 
Treatment and Diagnosis (DCTD), NCI. 
 
Pomalidomide is provided to the NCI under a Collaborative Agreement between the 
Pharmaceutical Collaborator and the DCTD, NCI (see Section 13.4). 
 
8.1.3 Agent Ordering and Agent Accountability 
 
8.1.3.1 
NCI-supplied agents may be requested by eligible participating Investigators (or their 
authorized designee) at each participating institution.  The CTEP-assigned protocol 
number must be used for ordering all CTEP-supplied investigational agents.  The 
eligible participating investigators at each participating institution must be registered 
with CTEP, DCTD through an annual submission of FDA Form 1572 (Statement of 
Investigator), NCI Biosketch, Agent Shipment Form, and Financial Disclosure Form 
(FDF).  If there are several participating investigators at one institution, CTEP-
supplied investigational agents for the study should be ordered under the name of one 
lead participating investigator at that institution. 
 
Sites can place orders for PMB-supplied agents only after enrollment and 
randomization onto the study.  Please provide the participant ID# when placing an 
order. 
 
Submit agent requests through the PMB Online Agent Order Processing (OAOP) 

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application.  Access to OAOP requires the establishment of a CTEP Identity and 
Access Management (IAM) account and the maintenance of an “active” account 
status, a “current” password, and active person registration status.  For questions 
about drug orders, transfers, returns, or accountability, call or email PMB any time.  
Refer to the PMB’s website for specific policies and guidelines related to agent 
management.   
 
8.1.3.2 
Agent Inventory Records – The investigator, or a responsible party designated by the 
investigator, must maintain a careful record of the receipt, dispensing and final 
disposition of all agents received from the PMB using the appropriate NCI 
Investigational Agent (Drug) Accountability Record (DARF) available on the CTEP 
forms page.  Store and maintain separate NCI Investigational Agent Accountability 
Records for each agent, strength, formulation and ordering investigator on this 
protocol. 
 
8.1.4 Investigator Brochure Availability 
 
The current versions of the IBs for the agents will be accessible to site investigators and research 
staff through the PMB OAOP application.  Access to OAOP requires the establishment of a 
CTEP IAM account and the maintenance of an “active” account status, a “current” password and 
active person registration status.  Questions about IB access may be directed to the PMB IB 
Coordinator via email. 
 
▪ Useful Links and Contacts 
• CTEP Forms, Templates, Documents:  http://ctep.cancer.gov/forms/ 
• NCI CTEP Investigator Registration:  RCRHelpDesk@nih.gov 
• PMB policies and guidelines: 
http://ctep.cancer.gov/branches/pmb/agent_management.htm  
• 
PMB Online Agent Order Processing (OAOP) application:  
https://ctepcore.nci.nih.gov/OAOP 
• CTEP Identity and Access Management (IAM) account: https://ctepcore.nci.nih.gov/iam/  
• CTEP IAM account help:  ctepreghelp@ctep.nci.nih.gov  
• IB Coordinator:  IBCoordinator@mail.nih.gov  
• PMB email:  PMBAfterHours@mail.nih.gov 
• PMB phone and hours of service: (240) 276-6575 Monday through Friday between 8:30 
am and 4:30 pm (ET) 
 
8.2 
Commercial Agent 
 
8.2.1 Daunorubicin and cytarabine liposome  
 
Product description:  Daunorubicin and cytarabine liposome (CPX-351, VyxeosTM) for 
injection is a commercially available, sterile, preservative-free, purple, lyophilized cake for 
reconstitution supplied in a single-dose clear glass vial as follows:  
• For injection: 44 mg daunorubicin and 100 mg cytarabine encapsulated in liposomes. 
 

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Each vial contains 44 mg daunorubicin and 100 mg cytarabine, and the following inactive 
ingredients:  distearoylphosphatidylcholine 454 mg, distearoylphosphatidylglycerol 132 mg, 
cholesterol HP 32 mg, copper gluconate 100 mg, triethanolamine 4 mg, and sucrose 2054 mg. 
 
Solution preparation:  Daunorubicin and cytarabine liposome is a cytotoxic drug. Follow 
applicable special handling and disposal procedures (https://www.osha.gov/hazardous-drugs). 
Daunorubicin and cytarabine liposome is supplied as a single-dose vial and does not contain any 
preservatives. Do not save any unused portions for later administration. 
 
Reconstitute and further dilute daunorubicin and cytarabine liposome prior to intravenous 
infusion. 
Reconstitution: 
• Calculate the daunorubicin and cytarabine liposome dose based on daunorubicin and 
individual patient's BSA. 
• Calculate the number of vials of daunorubicin and cytarabine liposome based on the 
daunorubicin dose. 
• Remove the appropriate number of vials of daunorubicin and cytarabine liposome from 
the refrigerator and equilibrate to the room temperature for 30 minutes. 
• Then, reconstitute each vial with 19 mL of Sterile Water for Injection using a sterile 
syringe and immediately thereafter start a 5-minute timer. 
• Carefully swirl the contents of the vial for 5 minutes while gently inverting the vial 
every 30 seconds. 
• Do not heat, vortex, or shake vigorously. 
• After reconstitution, let rest for 15 minutes. 
• The reconstituted product should be an opaque, purple, homogeneous dispersion, 
essentially free from visible particulates. After reconstitution (but before final dilution), 
each mL will contain 2.2 mg of daunorubicin and 5 mg of cytarabine. 
• Use the reconstituted solution immediately. If needed, store the reconstituted solution in 
the vial refrigerated at 2ºC to 8ºC (36°F to 46°F) for up to 4 hours. Note that the 
reconstituted product in the vial and the reconstituted product which has been diluted into 
an infusion solution are stable for a total of 4 hours (not 4 hours each) when stored at 2°C 
to 8°C. 
 
Dilution: 
• Calculate the volume of reconstituted daunorubicin and cytarabine liposome required 
using the following formula: 
[volume required (mL) = dose of daunorubicin (mg/m2) X patient's BSA (m2) ÷ 2.2 
(mg/mL)] 
• Gently invert each vial 5 times prior to withdrawing the reconstituted product for further 
dilution. 
• Aseptically withdraw the calculated volume of the reconstituted product from the vial(s) 
with a sterile syringe and transfer it to an infusion bag containing 500 mL of 0.9% 
Sodium Chloride Injection, USP or 5% Dextrose Injection, USP. There may be residual 
product remaining in the vial. Discard unused portion. 

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• Gently invert the bag to mix the solution. The dilution of the reconstituted product results 
in a deep purple, translucent, homogeneous dispersion, free from visible particulates. 
• If the diluted infusion solution is not used immediately, store in a refrigerator at 2ºC to 
8ºC (36°F to 46°F) for up to 4 hours. If the reconstituted solution in the vial was stored 
for 4 hours, the diluted infusion solution must be used immediately and cannot be stored 
for an additional 4 hours. 
• Parenteral drug products should be inspected visually for particulate matter and 
discoloration prior to administration, whenever solution and container permit. Only 
solutions without visible particles should be used. 
 
 
Route of administration: 
• For intravenous use only. 
• Do not mix daunorubicin and cytarabine liposome with or administer as an infusion with 
other drugs. 
• Administer daunorubicin and cytarabine liposome by constant intravenous infusion over 
90 minutes via an infusion pump through a central venous catheter or a peripherally 
inserted central catheter. An in-line membrane filter may be used for the intravenous 
infusion of Vyxeos, provided the minimum pore diameter of the filter is greater than or 
equal to 15 µm. 
• Flush the line after administration with 0.9% Sodium Chloride Injection, USP or 5% 
Dextrose Injection, USP. 
 
 
Agent Ordering:  Daunorubicin and cytarabine liposome is commercially available.  Refer to 
the daunorubicin and cytarabine liposome package insert for more information. 
 
9. 
STATISTICAL CONSIDERATIONS 
 
9.1 
Study Design/Endpoints 
 
This is a randomized two-arm study of daunorubicin and cytarabine liposome + pomalidomide 
versus daunorubicin and cytarabine liposome alone in newly diagnosed AML with preexisting 
MDS, CMML or MPN; t-AML; or AML with MRC based on cytogenetics or morphologic 
dysplasia without history of MDS/MPN.  We will test the null hypothesis that the CR/CRi rates 
in the two arms are the same.  We will enroll 39 patients in each arm.  We will test for futility 
after responses from the first 16 patients accrued to each arm are available.  The trial may be 
stopped for futility if the one-sided Fisher’s p-value is higher than 0.52.  
 
If the trial is not stopped for futility, 39 patients will be enrolled to each arm.  We will conclude 
that the combination therapy is better than daunorubicin and cytarabine liposome alone if the 
one-sided Fisher’s p-value at the end of the trial is lower than 0.05.  This design yields 80% 
power with the one-sided type I error rate of 0.05 assuming 48% CR/CRi rate in daunorubicin 
and cytarabine liposome alone arm and 77.3% CR/CRi rate in daunorubicin and cytarabine 
liposome + pomalidomide arm (alternative hypothesis).  The probability to stop for futility under 
the alternative hypothesis is 0.07.  The probability to stop for futility under the null hypothesis 

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major protocol treatment deviations.  Each patient will be assigned one of the following 
categories:  1) complete response, 2) partial response, 3) stable disease, 4) progressive disease, 5) 
early death from malignant disease, 6) early death from toxicity, 7) early death because of other 
cause, or 9) unknown (not assessable, insufficient data).  [Note:  By arbitrary convention, 
category 9 usually designates the “unknown” status of any type of data in a clinical database.] 
 
All of the patients who met the eligibility criteria (with the possible exception of those who 
received no study medication) should be included in the main analysis of the response rate.  
Patients in response categories 4-9 should be considered to have a treatment failure (disease 
progression).  Thus, an incorrect treatment schedule or drug administration does not result in 
exclusion from the analysis of the response rate.  Precise definitions for categories 4-9 will be 
protocol specific.  
 
All conclusions should be based on all eligible patients.  Subanalyses may then be performed on 
the basis of a subset of patients, excluding those for whom major protocol deviations have been 
identified (e.g., early death due to other reasons, early discontinuation of treatment, major 
protocol violations, etc.).  However, these subanalyses may not serve as the basis for drawing 
conclusions concerning treatment efficacy, and the reasons for excluding patients from the 
analysis should be clearly reported.   
 
9.6 
Data Safety Monitoring Board 
 
The conduct of this study will be overseen by the ETCTN DSMB.  The DSMB will be 
responsible for recommendations to the Principal Investigator and NCI regarding possible trial 
closure and/or early reporting of the study.  The study team (with the exception of the study 
statistician) will not have access to the summary outcome data until released by the DSMB. 
 
 
10. ADVERSE EVENTS:  LIST AND REPORTING REQUIREMENTS  
 
Adverse event (AE) monitoring and reporting is a routine part of every clinical trial.  The 
following list of AEs (Section 10.1) and the characteristics of an observed AE (Sections 10.2 and 
10.3) will determine whether the event requires expedited reporting via the CTEP Adverse Event 
Reporting System (CTEP-AERS) in addition to routine reporting. 
 
10.1 
Comprehensive Adverse Events and Potential Risks List (CAEPR) 
 
10.1.1 CAEPR for Pomalidomide (CC-4047, NSC 767909) 
The Comprehensive Adverse Events and Potential Risks list (CAEPR) provides a single list of 
reported and/or potential adverse events (AE) associated with an agent using a uniform 
presentation of events by body system. In addition to the comprehensive list, a subset, the 
Specific Protocol Exceptions to Expedited Reporting (SPEER), appears in a separate column and 
is identified with bold and italicized text. This subset of AEs (SPEER) is a list of events that are 
protocol specific exceptions to expedited reporting to NCI (except as noted below). Refer to the 
'CTEP, NCI Guidelines: Adverse Event Reporting Requirements' 
http://ctep.cancer.gov/protocolDevelopment/electronic applications/docs/aeguidelines.pdf for 

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3Sickle cell crises in patients with SCD is a rare but serious event.  
 
4Venous thromboembolic events (e.g., deep vein thrombosis and pulmonary embolism) and 
arterial thromboembolic events (e.g., myocardial infarction and stroke) have been observed to 
occur more frequently in multiple myeloma patients treated with pomalidomide and 
dexamethasone. 
  
5Infection includes all 75 sites of infection under the INFECTIONS AND INFESTATIONS 
SOC. 
 
Adverse events reported on Pomalidomide (CC-4047) trials, but for which there is 
insufficient evidence to suggest that there was a reasonable possibility that Pomalidomide 
(CC-4047) caused the adverse event: 
 
BLOOD AND LYMPHATIC SYSTEM DISORDERS - Blood and lymphatic system 
disorders - Other (sickle cell anemia with crisis)3; Febrile neutropenia 
CARDIAC DISORDERS - Atrial fibrillation; Cardiac arrest; Heart failure; Sinus tachycardia 
EAR AND LABYRINTH DISORDERS - Vertigo 
EYE DISORDERS - Blurred vision; Eye disorders - Other (eyelid swelling) 
GASTROINTESTINAL DISORDERS - Abdominal pain; Colonic perforation; Dry mouth; 
Dyspepsia; Enterocolitis; Vomiting 
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS - Chills; Death 
NOS; Disease progression; Malaise 
IMMUNE SYSTEM DISORDERS - Allergic reaction 
INVESTIGATIONS - CD4 lymphocytes decreased; CPK increased; Creatinine increased; 
Weight gain; Weight loss; White blood cell decreased 
METABOLISM AND NUTRITION DISORDERS - Dehydration; Hypercalcemia; 
Hyperglycemia; Hyperuricemia; Hypocalcemia; Hypokalemia 
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS - Arthralgia; Chest 
wall pain; Generalized muscle weakness; Muscle cramp; Myalgia; Pain in extremity 
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND 
POLYPS) - Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other 
(multiple myeloma, myelofibrosis, progression of MM); Tumor pain 
NERVOUS SYSTEM DISORDERS - Dysphasia; Headache; Intracranial hemorrhage; 
Ischemia cerebrovascular; Seizure; Syncope; Tremor 
PSYCHIATRIC DISORDERS - Anxiety; Depression; Insomnia 
RENAL AND URINARY DISORDERS - Hematuria   
REPRODUCTIVE SYSTEM AND BREAST DISORDERS - Pelvic pain 
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - Epistaxis; Nasal 
congestion; Oropharyngeal pain; Postnasal drip; Productive cough; Pulmonary hypertension; 
Respiratory failure; Respiratory, thoracic and mediastinal disorders - Other (sputum discolored) 
SKIN AND SUBCUTANEOUS TISSUE DISORDERS - Alopecia; Dry skin; Erythema 
multiforme; Hyperhidrosis; Pruritus 
VASCULAR DISORDERS - Vascular disorders - Other (hyperviscosity syndrome) 
 

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4The majority of hemorrhage events were mild. Major events, defined as symptomatic bleeding in a critical area or 
organ (e.g., eye, GI hemorrhage, GU hemorrhage, respiratory hemorrhage, reproductive hemorrhage), and nervous 
system [including fatal intracranial hemorrhage and cerebrovascular accident] have been reported. 
 
 
 
Adverse events reported on (Daunorubicin and Cytarabine) Liposome (CPX-351; Vyxeos) trials, but for 
which there is insufficient evidence to suggest that there was a reasonable possibility that (Daunorubicin and 
Cytarabine) Liposome (CPX-351; Vyxeos) caused the adverse event: 
 
BLOOD AND LYMPHATIC SYSTEM DISORDERS - Blood and lymphatic system disorders - Other 
(pancytopenia) 
CARDIAC DISORDERS - Heart failure 
INVESTIGATIONS - Ejection fraction decreased 
METABOLISM AND NUTRITION DISORDERS - Hyponatremia 
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS) - Leukemia 
secondary to oncology chemotherapy 
NERVOUS SYSTEM DISORDERS - Seizure; Syncope 
PSYCHIATRIC DISORDERS - Delirium 
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - Pulmonary edema 
 
 
Note: (Daunorubicin and Cytarabine) Liposome (CPX-351; Vyxeos) in combination with other agents could cause 
an exacerbation of any adverse event currently known to be caused by the other agent, or the combination may result 
in events never previously associated with either agent. 
 
 
Refer to the Package insert for daunorubicin and cytarabine liposome for more information. 
 
10.2 
Adverse Event Characteristics  
 
• CTCAE term (AE description) and grade:  The descriptions and grading scales found 
in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 
5.0 will be utilized for AE reporting.  All appropriate treatment areas should have access 
to a copy of the CTCAE version 5.0.  A copy of the CTCAE version 5.0 can be 
downloaded from the CTEP website 
http://ctep.cancer.gov/protocolDevelopment/electronic applications/ctc.htm. 
 
• For expedited reporting purposes only:   
- 
AEs for the agent that are bold and italicized in the CAEPR (i.e., those listed in the 
SPEER column, Section 10.1) should be reported through CTEP-AERS only if the 
grade is above the grade provided in the SPEER. 
- 
Other AEs for the protocol that do not require expedited reporting are outlined in 
Section 10.3.4. 
 
• Attribution of the AE: 
- 
Definite – The AE is clearly related to the study treatment. 
- 
Probable – The AE is likely related to the study treatment. 
- 
Possible – The AE may be related to the study treatment. 
- 
Unlikely – The AE is doubtfully related to the study treatment. 
- 
Unrelated – The AE is clearly NOT related to the study treatment. 

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10.3 
Expedited Adverse Event Reporting 
 
10.3.1 Rave-CTEP-AERS Integration 
 
The Rave Cancer Therapy Evaluation Program Adverse Event Reporting System (CTEP-
AERS) integration enables evaluation of Adverse Events (AEs) entered in Rave to 
determine whether they require expedited reporting and facilitates entry in CTEP-AERS 
for those AEs requiring expedited reporting.  Sites must initiate all AEs for this study in 
Medidata Rave. 
 
Adverse Events that occur after informed consent is signed and prior to start of treatment 
are collected in Medidata Rave using either the Adverse Baseline Symptoms form (SAE) 
or the Pre-treatment Biopsy Adverse Event form (AE and SAE that occur as a result of 
tissue biopsy specimen collection).  
 
Pre-existing medical conditions (formerly referred to as baseline AEs) identified during 
baseline assessment are not considered AEs and therefore should not be reported on the 
Pre-treatment Adverse Event form. If these pre-existing conditions worsen in severity, 
the investigator must reassess the event to determine if an expedited report is required. 
Whether or not an expedited report is required, the worsened event should be reported as 
a routine AE. 
 
Treatment-emergent AEs:  All AEs that occur after start of treatment are collected in 
Medidata Rave using the Adverse Event form, which is available for entry at each 
treatment course or reporting period and is used to collect AEs that start during the period 
or persist from the previous reporting period.  AEs that occur 30 Days after the Last 
Administration of the Investigational Agent/Intervention are collected using the Late 
Adverse Event form. 
 
Prior to sending AEs through the rules evaluation process, site staff should verify the 
following on the Adverse Event form in Rave: 
 
• The reporting period (course/cycle) is correct, and 
• AEs are recorded and complete (no missing fields) and the form is query-free.  
 
The CRA reports AEs in Rave at the time the Investigator learns of the event.  If the CRA 
modifies an AE, it must be re-submitted for rules evaluation. 
 
Upon completion of AE entry in Medidata Rave, the CRA submits the AE for rules 

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evaluation by completing the Expedited Reporting Evaluation form.  Both NCI and 
protocol-specific reporting rules evaluate the AEs submitted for expedited reporting.  A 
report is initiated in CTEP-AERS using information entered in Medidata Rave for AEs 
that meet reporting requirements.  The CRA completes the report by accessing CTEP-
AERS via a direct link on the Medidata Rave Expedited Reporting Evaluation form.  
Contact the CTSU Help Desk at 1-888-823-5923 or by email at ctsucontact@westat.com 
if you have any issues submitting an expedited report in CTEP-AERS. 
 
In the rare occurrence that internet connectivity is lost, a 24-hour notification is to be 
made to CTEP by telephone at 301-897-7497.  Once internet connectivity is restored, the 
24-hour notification that was phoned in must be entered immediately into CTEP-AERS 
using the direct link from Medidata Rave. 
 
Additional information about the CTEP-AERS integration is available on the CTSU 
members’ website: 
 
• Study specific documents:   Protocols > Documents> Protocol Related 
Documents> Adverse Event Reporting, and   
• Additional resources: Resources > CTSU Operations Information> User Guides 
& Help Topics. 
 
NCI requirements for SAE reporting are available on the CTEP website:  
 
NCI Guidelines for Investigators:  Adverse Event Reporting Requirements is available at 
https://ctep.cancer.gov/protocolDevelopment/electronic applications/docs/aeguidelines.p
df.  
 
10.3.2 Distribution of Adverse Event Reports 
 
CTEP-AERS is programmed for automatic electronic distribution of reports to the following 
individuals:  Principal Investigator and Adverse Event Coordinator(s) (if applicable) of the 
Corresponding Organization or Lead Organization, the local treating physician, and the Reporter 
and Submitter.  CTEP-AERS provides a copy feature for other e-mail recipients.  
 
10.3.3 Expedited Reporting Guidelines 
 
Use the NCI protocol number and the protocol-specific patient ID assigned during trial 
registration on all reports. 
 
Note:  A death on study requires both routine and expedited reporting, regardless of 
causality as long as the death occurred within 30 days after the last administration of the 
investigational agent.  Attribution to treatment or other cause must be provided. 

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Death due to progressive disease should be reported as Grade 5 “Disease progression” in the 
system organ class (SOC) “General disorders and administration site conditions.”  Evidence that 
the death was a manifestation of underlying disease (e.g., radiological changes suggesting tumor 
growth or progression: clinical deterioration associated with a disease process) should be 
submitted.  
 
 

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CTCAE SOC 
Adverse Event 
Grade 
Skin And Subcutaneous Tissue 
Disorders 
Infusion Reactions 
3 
Skin And Subcutaneous Tissue 
Disorders 
Rash 
3 
General Disorders And 
Administration Site Conditions 
Fever 
 
3 
Blood And Lymphatic System 
Disorders 
Febrile neutropenia 
3 
Infections And Infestations 
Infection 
3 
Gastrointestinal Disorders 
Nausea 
3 
General Disorders And 
Administration Site Conditions 
Fatigue 
3 
Metabolism And Nutrition 
Disorders 
Anorexia 
2 
Investigations 
Lymphocyte count decreased 
 
3 
Investigations 
Neutrophil count decreased 
3 
Investigations 
Platelet count decreased 
3 
Investigations 
White blood cell count 
decreased 
3 
 
 
10.4 
Routine Adverse Event Reporting 
 
All Adverse Events must be reported in routine study data submissions.  AEs reported 
expeditiously through CTEP-AERS must also be reported in routine study data 
submissions. 
 
10.5 
Pregnancy 
 
Although not an adverse event in and of itself, pregnancy as well as its outcome must be 
documented via CTEP-AERS.  In addition, the Pregnancy Information Form included within 
the NCI Guidelines for Adverse Event Reporting Requirements must be completed and 
submitted to CTEP.  Any pregnancy occurring in a patient or patient’s partner from the time of 
consent to 90 days after the last dose of study drug must be reported and then followed for 
outcome.  Newborn infants should be followed until 30 days old.  Please see the “NCI 
Guidelines for Investigators: Adverse Event Reporting Requirements for DCTD (CTEP and CIP) 
and DCP INDs and IDEs” (at http://ctep.cancer.gov/protocolDevelopment/adverse_effects.htm) 
for more details on how to report pregnancy and its outcome to CTEP.  
 
• Pregnancies and suspected pregnancies (including a positive pregnancy test regardless of 

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age or disease state) of a female patient or the partner of a male patient occurring while 
the patient is on pomalidomide or within 28 days after the patient’s last dose, are 
considered immediately reportable events.  Pomalidomide is to be discontinued 
immediately.  The pregnancy, suspected pregnancy, or positive pregnancy test must be 
reported via CTEP-AERS as a grade 4 event under: SOC pregnancy, puerperium and 
perinatal conditions; adverse event:  pregnancy, puerperium and perinatal conditions-
other, fetal exposure. 
o The female patient should be referred to an obstetrician-gynecologist, preferably 
one experienced in reproductive toxicity for further evaluation and counseling. 
 
• The Investigator will follow the female patient until completion of the pregnancy, and 
must make an amendment to the initial pregnancy report immediately regarding the 
outcome of the pregnancy and neonatal status (either normal or abnormal outcome). 
 
• If the outcome of the pregnancy was abnormal (including spontaneous or therapeutic 
abortion, fetal demise and congenital abnormalities), the Investigator should report the 
abnormal outcome as an amendment to the initial pregnancy report as soon as the as the 
Investigator has knowledge of the outcome.  
 
• All neonatal deaths and neonatal complications that occur within 28 days of birth should 
be reported, without regard to causality, as an amendment to the initial pregnancy report.  
In addition, any infant death after 28 days that the Investigator suspects is related to the in 
utero exposure to the pomalidomide should also be reported as an amendment within 24 
hours of the Investigator’s knowledge of the event. 
 
Male Patients 
• If a female partner of a male patient taking investigational product becomes pregnant, the 
male patient taking pomalidomide should notify the Investigator, and the pregnant female 
partner should be advised to call her healthcare provider immediately. 
 
10.6 
Secondary Malignancy 
 
A secondary malignancy is a cancer caused by treatment for a previous malignancy (e.g., 
treatment with investigational agent/intervention, radiation or chemotherapy). A secondary 
malignancy is not considered a metastasis of the initial neoplasm. 
 
CTEP requires all secondary malignancies that occur following treatment with an agent under an 
NCI IND/IDE be reported expeditiously via CTEP-AERS.  Three options are available to 
describe the event:  
 
• Leukemia secondary to oncology chemotherapy (e.g., acute myelocytic leukemia [AML])  
• Myelodysplastic syndrome (MDS)  
• Treatment-related secondary malignancy  
 
Any malignancy possibly related to cancer treatment (including AML/MDS) should also be 
reported via the routine reporting mechanisms outlined in each protocol.  

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10.7 
Second Malignancy 
 
A second malignancy is one unrelated to the treatment of a prior malignancy (and is NOT a 
metastasis from the initial malignancy).  Second malignancies require ONLY routine AE 
reporting unless otherwise specified.

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Assessment 
(CTCAE v5.0)  
Bone marrow 
biopsy 
X9 
 
 
 
 
 
 
X9 
 
 
 
X9 
X9 
 
 
Blood sample for 
biomarkers 
X10 
 
 
 
 
 
 
 
 
X10 
 
X10 
X10 
 
daunorubicin and 
cytarabine 
liposome 
 
X 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
Allopurinol11 
 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
Pomalidomide 4 
mg (ARM A 
only) 
 
 
 
 
 
 
 
 
 
X5 
X 
X 
 
 
 
Pomalidomide 
Education and 
Counseling (Arm 
A only) 
 
 
 
 
 
 
 
 
 
X12 
 
 
X12 
 
 
Pomalidomide 
Dispensing (Arm 
A only) 
 
 
 
 
 
 
 
 
 
X13 
 
 
 
 
 
Survival analysis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
1. 
Screening Windows for pre-study assessments are as follows: 
a. 
Complete history, physical exam, ECOG performance status, echocardiogram (does not need to be repeated after consent if done within 14 days of study 
treatment), bone marrow biopsy for disease assessment, and blood samples for biomarkers should be performed within 14 days prior to Day 1 of study 
treatment (daunorubicin and cytarabine liposome induction).   
b. 
All other screening evaluations including hematology and chemistry labs, and serum β-HCG pregnancy test (only applies to FCBP) must be performed within 3 
days prior to Day 1 of study treatment (daunorubicin and cytarabine liposome induction).  
 
2. 
Study visits should occur as scheduled in the time and events table unless otherwise specified.  If pomalidomide is not administered on Day 21 in Induction Phase, please 
follow scheduled assessments aligned with Days 15-20 (to be continued Days 22-28) in the induction table.  After pomalidomide is administered, please follow the 
assessments listed in the Induction Time and Events Table under “Daily after pomalidomide (Arm A) or eligibility for pomalidomide until discharge from hospital.”  Full 
hematologic recover is defined as (absolute neutrophil count [ANC] ≥1x109/L and platelet count ≥100 x 109/L). 
 
3. 
The end of treatment visit should only occur when patients permanently stop study treatment and should be performed within 30 days (+/-7 days) after the last dose of 
study medication.  Patients who have an ongoing ≥grade 2 or SAE at this visit will continue to be followed until the event is resolved or deemed irreversible by the 
investigator.  
  
4. 
See Section 6.4 for long-term follow up plan for this study. 
 
 
5. 
An FCBP is a female who:  1) has reached 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 (i.e., has had menses at any time in the 
preceding 24 consecutive months). 

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a. 
For patients in Arm A:  When starting pomalidomide, serum β-HCG pregnancy tests must occur within 10 – 14 days and again within 24 hours prior to 
initiation of pomalidomide.  FCBP with regular or no menstruation must have a pregnancy test weekly for the first 28 days; at discontinuation of pomalidomide 
and at Day 28 post the last dose of pomalidomide.  Females with irregular menstruation must have a pregnancy test weekly for the first 28 days and then every 
14 days while on study treatment (including breaks in treatment), at discontinuation of pomalidomide and at Day 14 and Day 28 post the last dose of 
pomalidomide (see Appendix D:  Pomalidomide Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods).  Pregnancy 
test during recovery should occur 3-4 weeks after the last dose of pomalidomide. 
6. 
Hematology labs:  CBC with differential 
 
7. 
During induction therapy hematology and serum chemistry labs will be performed twice daily on study Days 1-5 as outlined below.  
• 
Once daily labs 
o 
CBC with differential 
o 
CMP  
o 
BMP (obtained approximately 12 hrs [+/- 2h] after CMP on the same day) 
 
• 
Twice daily labs 
o 
Tumor lysis labs twice daily for Days 1-5. After day 5, tumor lysis labs should be performed only if clinically indicated. Tumor lysis labs consist of basic 
metabolic panel, uric acid, LDH, and phosphate. 
 
8. 
Starting on Day 6, CBC with differential and CMP should be collected three times a week at minimum until completion of pomalidomide or hematologic recovery 
(whichever occurs later). If patients are hospitalized, it is recommended to check a CBC and CMP daily while hospitalized. 
 
9. 
Bone marrow aspirate will be collected as follows(for additional information see Section 5): 
a. 
Prescreening: 
i. Bone marrow aspirate sample- 2.5 mL to be sent for next generation sequencing at Foundation Medicine, Inc.  
ii. Bone marrow aspirate sample- 2 mL to be sent for MRD analysis at Hematologics. 
iii. Bone marrow aspirate sample- 2.5 mL to be sent to University of North Carolina Molecular Genetics Laboratory 
iv. Correlative samples- 20 mL to the Tissue Procurement Facility UNC-Chapel Hill, 20 mL stored for future research 
v. Correlative samples- 20 mL to Luznik Laboratory at JHU, 20 mL stored for future research (from UNC and JHU participants only) 
b. 
Day 14: 
i. 40 ml bone marrow aspirate for correlative research to Luznik Laboratory at JHU (from UNC and JHU participants only) 
c. 
Day 28( +7 days): 
i. 40 ml bone marrow aspirate for correlative research to Luznik Laboratory at JHU (from UNC and JHU participants only) 
d. 
Response (between Days 30 and 64):  
i. A Bone marrow biopsy should be performed at full hematologic recovery or by day 49 (+/-3 days) if ANC <0.5x109/L and Platelets <25x109/L. 
Pomalidomide should be discontinued for at least 3 days prior to response assessment.  
ii. 2.5 ml bone marrow aspirate to University of North Carolina Molecular Genetics Laboratory 
iii. 20 ml bone marrow aspirate to Luznik Laboratory at JHU for correlative studies (from UNC and JHU participants only) 
iv. 20 ml bone marrow aspirate to the Tissue Procurement Facility for correlative studies 
v. 2 ml bone marrow aspirate to Hematologics for MRD analysis 
 
10. Correlative blood samples will be collected as described below (for additional information see Section 5.0): 
a. 
Pretreatment:  
i. 8-10 mL EDTA to be sent to University of North Carolina Molecular Genetics Laboratory 
ii. 20 ml sodium heparin tubes for correlative research to Luznik Laboratory at JHU (from UNC and JHU participants only) 
iii. 20 ml sodium heparin tubes for correlative research to the Tissue Procurement Facility UNC-Chapel Hill  

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Concomitant meds 
X--------------------------------------------------------------------------------------------------X 
X 
 
 
Toxicity Assessment 
(CTCAE v5.0) 
X--------------------------------------------------------------------------------------------------X 
X 
X 
 
Bone marrow biopsy  
 
 
 
 
 
 
X7 
X7 
 
 
Blood sample for biomarkers  
 
 
 
 
X8 
 
X8 
X8 
 
 
daunorubicin and cytarabine 
liposome Re-induction9 
X 
 
X 
 
 
 
 
 
 
 
Pomalidomide 4 mg PO (at 
least 48 hours after 
reinduction) Arm A only 
 
 
 
X 
X 
X 
 
 
 
Pomalidomide Education and 
Counseling (Arm A only) 
 
 
 
 
X10 
 
 
X10 
 
 
Pomalidomide Dispensing 
(Arm A only) 
 
 
 
 
X11 
 
 
 
 
 
Survival analysis  
 
 
 
 
 
 
 
 
 
X 
 
*Reinduction with daunorubicin and cytarabine liposome must be initiated by Day 21.  
( ) denotes other possible start days for daunorubicin and cytarabine liposome re-induction chemotherapy and subsequent assessments performed as shown above 
taking into account the delayed start. 
 
1. 
Study visits should occur as scheduled in the time and events table unless otherwise specified.  If pomalidomide is not administered on Day 21 in Induction Phase, please 
follow scheduled assessments aligned with Days 15-20 (to be continued Days 22-28) in the induction table.  After pomalidomide is administered, please follow the 
assessments listed in the Induction Time and Events Table under “Daily after pomalidomide (Arm A) or eligibility for pomalidomide until discharge from hospital.”  Full 
hematologic recover is defined as (absolute neutrophil count [ANC] ≥1x109/L and platelet count ≥100 x 109/L). 
 
2. 
The end of treatment visit should only occur when patients permanently stop study treatment and should be performed within 30 days (+/-7 days) after the last dose of 
study medication.  Patients who have an ongoing ≥grade 2 or SAE at this visit will continue to be followed until the event is resolved or deemed irreversible by the 
investigator. A response bone marrow aspirate/biopsy should be performed by day 49 +/- 3 days from day 1 of re-induction daunorubicin and cytarabine liposome if 
ANC <0.5x109/L and platelets <25x109/L 
  
3. 
See Section 6.4 for long-term follow up plan for this study. 
 
4. 
An FCBP is a female who:  1) has reached 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 (i.e., has had menses at any time in the 
preceding 24 consecutive months). 
a. 
For patients in Arm A:  When starting pomalidomide, serum β-HCG pregnancy tests must occur within 10 – 14 days and again within 24 hours prior to 
initiation of pomalidomide.  FCBP with regular or no menstruation must have a pregnancy test weekly for the first 28 days; at discontinuation of pomalidomide 
and at Day 28 post the last dose of pomalidomide.  Females with irregular menstruation must have a pregnancy test weekly for the first 28 days and then every 
14 days while on study treatment (including breaks in treatment), at discontinuation of pomalidomide and at Day 14 and Day 28 post the last dose of 
pomalidomide (see Appendix D:  Pomalidomide Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods).  Pregnancy 
test during recovery should occur 3-4 weeks after the last dose of pomalidomide. 

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5. 
During re-induction therapy hematology and serum chemistry labs will be performed once daily on study Days 1-3 as outlined below.  
• 
Once daily labs 
o 
CBC with differential 
o 
CMP  
 
6. 
After completion of daunorubicin and cytarabine liposome reinduction and prior to pomalidomide administration, BMP should be done every other day and CMP should 
be done every other day on alternating days. 
 
7. 
Bone marrow aspirate will be collected as follows(for additional information see Section 5): 
a. 
Prescreening: 
i. Bone marrow aspirate sample- 2.5 mL to be sent for next generation sequencing at Foundation Medicine, Inc.  
ii. Bone marrow aspirate sample- 2 mL to be sent for MRD analysis at Hematologics.  
iii. Bone marrow aspirate sample- 2.5 mL to be sent to University of North Carolina Molecular Genetics Laboratory 
iv. Correlative samples- 20 mL to Tissue Procurement Facility UNC-Chapel Hill, 20 mL stored for future research 
v. Correlative samples- 20 mL to Luznik Laboratory, 20 mL stored for future research (from UNC and JHU participants only) 
b. 
Day 14: 
i. 40 ml bone marrow aspirate for correlative research to Luznik Laboratory (from UNC and JHU participants only) 
c. 
Day 28( +7 days): 
i. 40 ml bone marrow aspirate for correlative research to Luznik Laboratory (from UNC and JHU participants only) 
d. 
Response (between Days 30 and 64):  
i. 2.5 ml bone marrow aspirate to University of North Carolina Molecular Genetics Laboratory 
ii. 20 ml bone marrow aspirate to Luznik Laboratory for correlative studies (from UNC and JHU participants only) 
iii. 20 ml bone marrow aspirate to the Tissue Procurement Facility UNC-Chapel Hill for correlative studies 
iv. 2 ml bone marrow aspirate to Hematologics for MRD analysis 
 
8. 
Correlative blood samples will be collected as described below (for additional information see Section 5.0): 
a. 
Pretreatment:  
i. 8-10 mL EDTA to be sent to University of North Carolina Molecular Genetics Laboratory 
ii. 20 ml sodium heparin tubes for correlative research to Luznik Laboratory (from UNC and JHU participants only) 
iii. 20 ml sodium heparin tubes for correlative research to the Tissue Procurement Facility UNC-Chapel Hill  
b. 
Day 21 (For Arm A, this should be before pomalidomide):  
i. 
20 ml sodium heparin tubes for correlative research to Luznik Laboratory (from UNC and JHU participants only) 
ii. 
20 ml sodium heparin tubes for correlative research to the Tissue Procurement Facility UNC-Chapel Hill  
c. 
Day 28 (+ 7 days):  
i. 40 ml sodium heparin tube for correlative research to Luznik Laboratory (from UNC and JHU participants only) 
d. 
At Response (between Days 30 and 64):  
i. 8-10 mL EDTA to be sent to University of North Carolina Molecular Genetics Laboratory 
ii. 20 ml sodium heparin tubes for correlative research to Luznik Laboratory (from UNC and JHU participants only) 
iii. 20 ml sodium heparin tubes for correlative research to the Tissue Procurement Facility UNC-Chapel Hill  
 
9. 
Daunorubicin and cytarabine liposome re-induction = liposomal daunorubicin 44 mg/m2 and cytarabine 100 mg/m2 IV Days 1 and 3 of re-induction. 
 
10. For patients in Arm A:  The Pomalidomide Education and Counseling Guidance Document (Appendix E) must be completed and signed by a trained counselor at the 

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participating site prior to each dispensing of Pomalidomide treatment.  A copy of this document must be maintained in the patient records.  The Pomalidomide 
Information Sheet (Appendix F) will be given to each patient receiving pomalidomide treatment.  The patient must read this document prior to starting pomalidomide 
study treatment and each time they receive a new supply of study drug. 
 
11. Only enough pomalidomide for the one cycle of study treatment may be provided to the patient each cycle. 
 
 

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4. 
Echocardiogram should be performed within 7 days prior to 1st cycle of consolidation and if clinically indicated.  
5. 
Hematology labs:  CBC with differential. 
6. 
Hematology labs (CBC with differential) and CMP to be drawn at a minimum twice weekly during recovery period (i.e., Day 6 until Day 1 of subsequent 
cycle) of each consolidation phase. 
7. 
Concomitant Medications and Toxicity Assessments should occur once weekly during recovery period (i.e., Day 6 until Day 1 of subsequent cycle) of 
consolidation 
8. 
In patients who develop cardiomyopathy, have an LEVF <50 prior to starting consolidation, who exceed lifetime anthracycline dose of > 430 mg/m2 (or >280 
mg/m2 with prior mediastinal radiation) or have any other contraindications to daunorubicin and cytarabine liposome consolidation, moderate to high dose (1-3 
g/m2 IV Q12 hours Days 1, 3 and 5) cytarabine can be used in place of daunorubicin and cytarabine liposome for consolidation. 
9. 
See Section 6.4 for long-term follow up plan for this study. 
 

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12. MEASUREMENT OF EFFECT 
 
12.1 
Antitumor Effect – Hematologic Tumors 
 
Patients will be evaluated using ELN AML Response Criteria (2017) [2].  See Appendix J. 
 
12.1.1 Definitions 
 
Evaluable for Toxicity.  All patients will be evaluable for toxicity from the time of their first 
treatment with daunorubicin and cytarabine liposome. 
 
Evaluable for Objective Response.  Only those patients who have measurable disease present at 
baseline, have received at least one cycle of induction therapy, and have had their disease re-
evaluated will be considered evaluable for response.  These patients will have their response 
classified according to the definitions in Appendix J. 
 
13. STUDY OVERSIGHT AND DATA REPORTING / REGULATORY 
REQUIREMENTS 
 
Adverse event lists, guidelines, and instructions for AE reporting can be found in Section 10 
(Adverse Events: List and Reporting Requirements). 
 
13.1 
Study Oversight 
 
This protocol is monitored at several levels, as described in this section.  The Protocol Principal 
Investigator is responsible for monitoring the conduct and progress of the clinical trial, including 
the ongoing review of accrual, patient-specific clinical and laboratory data, and routine and 
serious adverse events; reporting of expedited adverse events; and accumulation of reported 
adverse events from other trials testing the same drug(s).  The Protocol Principal Investigator and 
statistician have access to the data at all times through the CTMS web-based reporting portal.   
 
All Study Investigators at participating sites who register/enroll patients on a given protocol are 
responsible for timely submission of data via Medidata Rave and timely reporting of adverse 
events for that particular study.  This includes timely review of data collected on the electronic 
CRFs submitted via Medidata Rave. 
 
All studies are also reviewed in accordance with the enrolling institution’s data safety monitoring 
plan. 
 
13.2 
Data Reporting 
 
Medidata Rave is a clinical data management system being used for data collection for this 
trial/study.  Access to the trial in Rave is controlled through the CTEP-IAM system and role 
assignments.   
 

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Requirements to access Rave via iMedidata: 
 
• 
A valid account, and  
• 
Assigned a Rave role on the LPO or PO roster at the enrolling site of:  Rave CRA, Rave 
Read Only, Rave CRA (LabAdmin), Rave SLA, or Rave Investigator.   
Rave role requirements: 
 
o Rave CRA or Rave CRA (Lab Admin) role, must have a minimum of an 
Associate Plus (AP) registration type, 
o Rave Investigator role, must be registered as an Non-Physician Investigator 
(NPIVR) or Investigator (IVR), and 
o Rave Read Only role, site staff must have at a minimum an Associates (A) 
registration type. 
• 
Refer to https://ctep.cancer.gov/investigatorResources/default.htm for registration types 
and documentation required. 
 
If the study has a DTL, individuals requiring write access to Rave must also be assigned the 
appropriate Rave tasks on the DTL. 
 
Upon initial site registration approval for the study in Regulatory Support System (RSS), all 
persons with Rave roles assigned on the appropriate roster will be sent a study invitation email 
from iMedidata.  To accept the invitation, site staff must either click on the link in the email or 
log in to iMedidata via the CTSU members’ website  under Data Management > Rave Home and 
click to accept the invitation in the Tasks pane located in the upper right-corner of the iMedidata 
screen.  Site staff will not be able to access the study in Rave until all required Medidata and 
study specific trainings are completed.  Trainings will be in the form of electronic learnings 
(eLearnings) and can be accessed by clicking on the eLearning link in the Tasks pane located in 
the upper right corner of the iMedidata screen.  If an eLearning is required for a study and has 
not yet been taken, the link to the eLearning will appear under the study name in the Studies pane 
located in the center of the iMedidata screen; once the successful completion of the eLearning 
has been recorded, access to the study in Rave will be granted, and a Rave EDC link will replace 
the eLearning link under the study name.  
 
Site staff that have not previously activated their iMedidata/Rave account at the time of initial 
site registration approval for the study in RSS will receive a separate invitation from iMedidata 
to activate their account.  Account activation instructions are located on the CTSU website in the 
Data Management section under the Rave resource materials (Medidata Account Activation and 
Study Invitation Acceptance).  Additional information on iMedidata/Rave is available on the 
CTSU members’ website in the Data Management > Rave section at www.ctsu.org/RAVE/ or by 
contacting the CTSU Help Desk at 1-888-823-5923 or by e-mail at ctsucontact@westat.com.   
 
13.2.1 Method 
 
This study will be monitored by the Clinical Trials Monitoring Service (CTMS).  Data will be 
submitted to CTMS at least once every two weeks via Medidata Rave (or other modality if 
approved by CTEP).  Information on CTMS reporting is available at:  

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http://www.theradex.com/clinicalTechnologies/?National-Cancer-Institute-NCI-11.  On-site 
audits will be conducted on an 18-36 month basis as part of routine cancer center site visits. 
More frequent audits may be conducted if warranted by accrual or due to concerns regarding 
data quality or timely submission.  For CTMS monitored studies, after users have activated their 
accounts, please contact the Theradex Help Desk at (609) 619-7862 or by email at 
CTMSSupport@theradex.com for additional support with Rave and completion of CRFs. 
 
13.2.2 Responsibility for Data Submission 
 
For ETCTN trials, it is the responsibility of the PI(s) at the site to ensure that all investigators at 
the ETCTN Sites understand the procedures for data submission for each ETCTN protocol and 
that protocol specified data are submitted accurately and in a timely manner to the CTMS via the 
electronic data capture system, Medidata Rave.   
 
Data are to be submitted via Medidata Rave to CTMS on a real-time basis, but no less than once 
every 2 weeks.  The timeliness of data submissions and timeliness in resolving data queries will 
be tracked by CTMS.  Metrics for timeliness will be followed and assessed on a quarterly basis.  
For the purpose of Institutional Performance Monitoring, data will be considered delinquent if it 
is greater than 4 weeks past due. 
 
Data from Medidata Rave and CTEP-AERS is reviewed by the CTMS on an ongoing basis as 
data is received.  Queries will be issued by CTMS directly within Rave.  The queries will appear 
on the Task Summary Tab within Rave for the CRA at the ETCTN to resolve.  Monthly web-
based reports are posted for review by the Drug Monitors in the IDB, CTEP.  Onsite audits will 
be conducted by the CTMS to ensure compliance with regulatory requirements, GCP, and NCI 
policies and procedures with the overarching goal of ensuring the integrity of data generated 
from NCI-sponsored clinical trials, as described in the ETCTN Program Guidelines, which may 
be found on the CTEP 
(http://ctep.cancer.gov/protocolDevelopment/electronic applications/adverse events.htm)  and 
CTSU websites. 
 
CTMS will utilize a core set of eCRFs that are Cancer Data Standards Registry and Repository 
(caDSR) compliant (http://cbiit.nci.nih.gov/ncip/biomedical-informatics-
resources/interoperability-and-semantics/metadata-and-models).  Customized eCRFs will be 
included when appropriate to meet unique study requirements.  The PI is encouraged to review 
the eCRFs, working closely with CTMS to ensure prospectively that all required items are 
appropriately captured in the eCRFs prior to study activation.  CTMS will prepare the eCRFs 
with built-in edit checks to the extent possible to promote data integrity. 
 
CDUS data submissions for ETCTN trials activated after March 1, 2014, will be carried out by 
the CTMS contractor, Theradex.  CDUS submissions are performed by Theradex on a monthly 
basis.  The trial’s lead institution is responsible for timely submission to CTMS via Rave, as 
above. 
 
Further information on data submission procedures can be found in the ETCTN Program 
Guidelines 

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(http://ctep.cancer.gov/protocolDevelopment/electronic applications/adverse events.htm). 
 
13.3 
Data Quality Portal 
 
The Data Quality Portal (DQP) provides a central location for site staff to manage 
unanswered queries and form delinquencies, monitor data quality and timeliness, 
generate reports, and review metrics.  
 
The DQP is located on the CTSU members’ website under Data Management.  The Rave 
Home section displays a table providing summary counts of Total Delinquencies and 
Total Queries.  DQP Queries, DQP Delinquent Forms, DQP Form Status and the DQP 
Reports modules are available to access details and reports of unanswered queries, 
delinquent forms, forms with current status and timeliness reports.  Review the DQP 
modules on a regular basis to manage specified queries and delinquent forms. 
 
The DQP is accessible by site staff that are rostered to a site and have access to the CTSU 
website.  Staff that have Rave study access can access the Rave study data using a direct 
link on the DQP. 
 
To learn more about DQP use and access, click on the Help icon displayed on the Rave 
Home, DQP Queries, DQP Delinquent Forms, DQP Form Status, and DQP Reports 
modules. 
 
This study does not use the Rave Calendaring functionality and therefore the DQP 
Delinquent Forms module will not include details for this study, and the DQP Summary 
table on the Rave Home page will display N/A for the Total Delinquencies summary 
count. 
13.4 
Collaborative Agreements Language 
 
The agent(s) supplied by CTEP, DCTD, NCI used in this protocol is/are provided to the NCI 
under a Collaborative Agreement (CRADA, CTA, CSA) between the Pharmaceutical 
Company(ies) (hereinafter referred to as “Collaborator(s)”) and the NCI Division of Cancer 
Treatment and Diagnosis.  Therefore, the following obligations/guidelines, in addition to the 
provisions in the “Intellectual Property Option to Collaborator”  
(http://ctep.cancer.gov/industryCollaborations2/intellectual property.htm) contained within the 
terms of award, apply to the use of the Agent(s) in this study: 
 
1. Agent(s) may not be used for any purpose outside the scope of this protocol, nor can 
Agent(s) be transferred or licensed to any party not participating in the clinical study.  
Collaborator(s) data for Agent(s) are confidential and proprietary to Collaborator(s) and shall 
be maintained as such by the investigators.  The protocol documents for studies utilizing 
Agents contain confidential information and should not be shared or distributed without the 
permission of the NCI.  If a copy of this protocol is requested by a patient or patient’s family 
member participating on the study, the individual should sign a confidentiality agreement.  A 
suitable model agreement can be downloaded from: http://ctep.cancer.gov. 

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2. For a clinical protocol where there is an investigational Agent used in combination with 
(an)other Agent(s), each the patient of different Collaborative Agreements, the access to and 
use of data by each Collaborator shall be as follows (data pertaining to such combination use 
shall hereinafter be referred to as "Multi-Party Data”): 
 
a. NCI will provide all Collaborators with prior written notice regarding the existence and 
nature of any agreements governing their collaboration with NCI, the design of the 
proposed combination protocol, and the existence of any obligations that would tend to 
restrict NCI's participation in the proposed combination protocol. 
 
b. Each Collaborator shall agree to permit use of the Multi-Party Data from the clinical trial 
by any other Collaborator solely to the extent necessary to allow said other Collaborator 
to develop, obtain regulatory approval or commercialize its own Agent. 
 
c. Any Collaborator having the right to use the Multi-Party Data from these trials must 
agree in writing prior to the commencement of the trials that it will use the Multi-Party 
Data solely for development, regulatory approval, and commercialization of its own 
Agent. 
 
3. Clinical Trial Data and Results and Raw Data developed under a Collaborative Agreement 
will be made available to Collaborator(s), the NCI, and the FDA, as appropriate and unless 
additional disclosure is required by law or court order as described in the IP Option to 
Collaborator (http://ctep.cancer.gov/industryCollaborations2/intellectual_property.htm).  
Additionally, all Clinical Data and Results and Raw Data will be collected, used and 
disclosed consistent with all applicable federal statutes and regulations for the protection of 
human patients, including, if applicable, the Standards for Privacy of Individually 
Identifiable Health Information set forth in 45 C.F.R. Part 164. 
 
4. When a Collaborator wishes to initiate a data request, the request should first be sent to the 
NCI, who will then notify the appropriate investigators (Group Chair for Cooperative Group 
studies, or PI for other studies) of Collaborator's wish to contact them. 
 
5. Any data provided to Collaborator(s) for Phase 3 studies must be in accordance with the 
guidelines and policies of the responsible Data Monitoring Committee (DMC), if there is a 
DMC for this clinical trial. 
 
6. Any manuscripts reporting the results of this clinical trial must be provided to CTEP by the 
Group office for Cooperative Group studies or by the principal investigator for non-
Cooperative Group studies for immediate delivery to Collaborator(s) for advisory review and 
comment prior to submission for publication.  Collaborator(s) will have 30 days from the 
date of receipt for review.  Collaborator shall have the right to request that publication be 
delayed for up to an additional 30 days in order to ensure that Collaborator’s confidential and 
proprietary data, in addition to Collaborator(s)’s intellectual property rights, are protected.  
Copies of abstracts must be provided to CTEP for forwarding to Collaborator(s) for courtesy 
review as soon as possible and preferably at least three (3) days prior to submission, but in 
any case, prior to presentation at the meeting or publication in the proceedings.  Press 

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releases and other media presentations must also be forwarded to CTEP prior to release.  
Copies of any manuscript, abstract and/or press release/ media presentation should be sent to: 
 
Email:  ncicteppubs@mail.nih.gov 
 
The Regulatory Affairs Branch will then distribute them to Collaborator(s).  No publication, 
manuscript or other form of public disclosure shall contain any of Collaborator’s confidential/ 
proprietary information. 
 
13.5 
Incidental/Secondary Findings Disclosure Procedure 
 
Results will be placed in the patient’s medical record if confirmed by a CLIA-certified laboratory 
and signed off by the MTB.  Notification of results of reportable genetic profiling will be 
provided to the patient’s treating physician who will be responsible for sharing results with their 
patient.  Negative reports (i.e. no alteration found) will also be reported.  If an incidental 
germline mutation is discovered that has clinical implications with respect to hereditary cancer 
predisposition, for example, this information will be conveyed through formal genetic 
counseling.  Along with the results, the participant’s physician will explain the implications of 
the testing, including whether their genetic profile renders them eligible for a specific therapy or 
clinical trial, and/or if their genetic profile carries any prognostic significance for their disease.  
Participants will be informed that researchers may contact them in the future, to request their 
participation in new research or in the event new discoveries or therapies become available that 
may be applicable to their specific genetic profile. 
 

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14. REFERENCES 
 
 
1. 
Dohner, H., et al., Diagnosis and management of acute myeloid leukemia in adults: 
recommendations from an international expert panel, on behalf of the European 
LeukemiaNet. Blood, 2010. 115(3): p. 453-74. 
2. 
Dohner, H., et al., Diagnosis and management of AML in adults: 2017 ELN 
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affects circulating TC1, TH1, TH17 and TREG cells. BMC Immunol, 2010. 11: p. 38. 
54. 
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140(11): p. 1200-1228. 
 
 
 

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APPENDIX A 
PERFORMANCE STATUS CRITERIA 
 
ECOG Performance Status Scale 
Karnofsky Performance Scale 
Grade 
Descriptions 
Percent 
Description 
0 
Normal activity. Fully active, able 
to carry on all pre-disease 
performance without restriction. 
100 
Normal, no complaints, no evidence 
of disease. 
90 
Able to carry on normal activity; 
minor signs or symptoms of disease. 
1 
Symptoms, but ambulatory. 
Restricted in physically strenuous 
activity, but ambulatory and able 
to carry out work of a light or 
sedentary nature (e.g., light 
housework, office work). 
80 
Normal activity with effort; some 
signs or symptoms of disease. 
70 
Cares for self, unable to carry on 
normal activity or to do active work. 
2 
In bed <50% of the time. 
Ambulatory and capable of all 
self-care, but unable to carry out 
any work activities. Up and about 
more than 50% of waking hours. 
60 
Requires occasional assistance, but 
is able to care for most of his/her 
needs. 
50 
Requires considerable assistance and 
frequent medical care. 
3 
In bed >50% of the time. Capable 
of only limited self-care, confined 
to bed or chair more than 50% of 
waking hours. 
40 
Disabled, requires special care and 
assistance. 
30 
Severely disabled, hospitalization 
indicated. Death not imminent. 
4 
100% bedridden. Completely 
disabled. Cannot carry on any self-
care. Totally confined to bed or 
chair. 
20 
Very sick, hospitalization indicated. 
Death not imminent. 
10 
Moribund, fatal processes 
progressing rapidly. 
5 
Dead. 
0 
Dead. 
 
 
 

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APPENDIX D 
POMALIDOMIDE RISKS OF FETAL EXPOSURE, PREGNANCY 
TESTING GUIDELINES AND ACCEPTABLE BIRTH CONTROL 
METHODS 
 
1.1 
Risks Associated with Pregnancy 
Pomalidomide was teratogenic in both rats and rabbits when administered during the period of 
organogenesis. Pomalidomide is an analogue of thalidomide. Thalidomide is a known human 
teratogen that causes severe life-threatening human birth defects. If pomalidomide is taken 
during pregnancy, it can cause birth defects or death to an unborn baby. 
The teratogenic effect of pomalidomide in humans cannot be ruled out. Therefore, a pregnancy 
prevention program must be followed. 
 
1.1.1 
Definition of Females of Childbearing Potential (FCBP) 
A FCBP is 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). 
 
1.1.2 
Definition of Females Not of Childbearing Potential (FNCBP) 
Females who do not meet the above definition of FCBP should be classified as FNCBP. 
 
1.2 
Counseling 
 
1.2.1 
Females of Childbearing Potential 
For a FCBP, pomalidomide is contraindicated unless all of the following are met (ie, all FCBP 
must be counseled concerning the following risks and requirements prior to the start of 
pomalidomide):  
• She understands the potential teratogenic risk to the unborn child 
• She understands the need for effective contraception, without interruption, 28 days 
before starting pomalidomide, throughout the entire duration of pomalidomide, 
during dose interruptions and for at least 28 days after the last dose of pomalidomide 
• She understands and agrees to inform the Investigator if a change or stop of method 
of contraception is needed 
• She must be capable of complying with effective contraceptive measures 
• She is informed and understands the potential consequences of pregnancy and the 
need to notify her study doctor immediately if there is a risk of pregnancy 
• She understands the need to commence pomalidomide as soon as it is dispensed 
following a negative pregnancy test 

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• She understands and accepts the need to undergo pregnancy testing based on the 
frequency outlined in this plan (Section 0) and in the Informed Consent 
• She acknowledges that she understands the hazards pomalidomide can cause to an 
unborn fetus and the necessary precautions associated with the use of pomalidomide. 
The Investigator must ensure that a FCBP: 
• Complies with the conditions of the pregnancy prevention plan, including 
confirmation that she has an adequate level of understanding 
• Acknowledges the aforementioned requirements. 
 
1.2.2 
Females Not of Childbearing Potential 
For a FNCBP, pomalidomide is contraindicated unless all of the following are met (ie, all 
FNCBP must be counseled concerning the following risks and requirements prior to the start of 
pomalidomide):  
• She acknowledges she understands the hazards pomalidomide can cause to an unborn 
fetus and the necessary precautions associated with the use of pomalidomide. 
 
1.2.3 
Males 
The effect of pomalidomide on sperm development is not known and has not been studied. The 
risk to an unborn baby in females of child bearing potential whose male partner is receiving 
pomalidomide is unknown at this time. Therefore, male subjects taking pomalidomide must meet 
the following conditions (ie, all males must be counseled concerning the following risks and 
requirements prior to the start of pomalidomide): 
• Understand the potential teratogenic risk if engaged in sexual activity with a pregnant 
female or a FCBP 
• Understand the need for the use of a condom even if he has had a vasectomy, if 
engaged in sexual activity with a pregnant female or a FCBP 
• Understand the potential teratogenic risk if the subject donates semen or sperm. 
 
1.3 
Contraception 
 
1.3.1 
Female Subjects of Childbearing Potential 
Females of childbearing potential enrolled in this protocol must agree to use two reliable forms 
of contraception simultaneously or to practice complete abstinence (True abstinence is 
acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic 
abstinence [eg calendar, ovulation, symptothermal or post-ovulation methods] and withdrawal 
are not acceptable methods of contraception.) from heterosexual contact during the following 
time periods related to this study: 1) for at least 28 days before starting pomalidomide; 2) while 
taking pomalidomide; 3) during dose interruptions; and 4) for at least 28 days after the last dose 
of pomalidomide.  

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The two methods of reliable contraception must include one highly effective method and one 
additional effective (barrier) method. If the below contraception methods are not appropriate for 
the FCBP, she must be referred to a qualified provider of contraception methods to determine the 
medically effective contraception method appropriate to the subject. The following are examples 
of highly effective and additional effective methods of contraception: 
• Examples of highly effective methods: 
− Intrauterine device (IUD) 
− Hormonal (birth control pills, injections, implants, levonorgestrel-releasing 
intrauterine system [IUS], medroxyprogesterone acetate depot injections, 
ovulation inhibitory progesterone-only pills [e.g. desogestrel]) 
− Tubal ligation 
− Partner’s vasectomy 
• Examples of additional effective methods: 
− Male condom 
− Diaphragm 
− Cervical Cap 
Implants and levonorgestrel-releasing intrauterine systems are associated with an increased risk 
of infection at the time of insertion and irregular vaginal bleeding. Prophylactic antibiotics 
should be considered particularly in subjects with neutropenia.  
 
1.3.2 
Male Subjects 
Male subjects must practice complete abstinence (True abstinence is acceptable when this is in 
line with the preferred and usual lifestyle of the subject. Periodic abstinence [eg calendar, 
ovulation, symptothermal or post-ovulation methods] and withdrawal are not acceptable methods 
of contraception.) or agree to use a condom during sexual contact with a pregnant female or a 
FCBP while taking pomalidomide, during dose interruptions and for at least 28 days after the last 
dose of pomalidomide, even if he has undergone a successful vasectomy.  
 
1.4 
Pregnancy Testing 
Medically supervised pregnancy tests with a minimum sensitivity of 25 mIU/mL must be 
performed for FCBP. 
Females of childbearing potential must have two negative pregnancy tests (sensitivity of at least 
25 mIU/mL) prior to starting pomalidomide. The first pregnancy test must be performed within 
10 to 14 days prior to the start of pomalidomide and the second pregnancy test must be 
performed within 24 hours prior to the start of pomalidomide. The subject may not receive 
pomalidomide until the study doctor has verified that the results of these pregnancy tests are 
negative. 

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Females of childbearing potential with regular or no menstrual cycles must agree to have 
pregnancy tests weekly for the first 28 days of study participation, at study discontinuation, and 
at Day 28 following the last dose of pomalidomide.  
Females of childbearing potential with irregular menstrual cycles must agree to have pregnancy 
tests weekly for the first 28 days of study participation and then every 14 days while taking 
pomalidomide, at study discontinuation, and at Days 14 and 28 following the last dose of 
pomalidomide.  
 
1.5 
Pregnancy Precautions for Pomalidomide Use 
 
1.5.1 
Before Starting Pomalidomide 
 
1.5.1.1 
Female Subjects of Childbearing Potential 
Females of childbearing potential must have two negative pregnancy tests (sensitivity of at least 
25 mIU/mL) prior to starting pomalidomide. The first pregnancy test must be performed within 
10 to 14 days prior to the start of pomalidomide and the second pregnancy test must be 
performed within 24 hours prior to the start of pomalidomide. The subject may not receive 
pomalidomide until the study doctor has verified that the results of these pregnancy tests are 
negative. 
Females of childbearing potential must use two reliable forms of contraception simultaneously, 
or practice complete abstinence (True abstinence is acceptable when this is in line with the 
preferred and usual lifestyle of the subject. Periodic abstinence [eg calendar, ovulation, 
symptothermal or post-ovulation methods] and withdrawal are not acceptable methods of 
contraception.) from heterosexual contact for at least 28 days before starting pomalidomide. 
 
1.5.1.2 
Male Subjects 
Male subjects must agree to practice complete abstinence (True abstinence is acceptable when 
this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence [eg 
calendar, ovulation, symptothermal or post-ovulation methods] and withdrawal are not 
acceptable methods of contraception.) or agree to use a condom during sexual contact with a 
pregnant female or a FCBP while taking pomalidomide, during dose interruptions and for at least 
28 days after the last dose of pomalidomide, even if he has undergone a successful vasectomy.  
 
1.5.2 
During and After Study Participation 
 
1.5.2.1 
Female Subjects 
• Females of childbearing potential with regular or no menstrual cycles must agree to 
have pregnancy tests weekly for the first 28 days of study participation, at study 
discontinuation, and at Day 28 following the last dose of pomalidomide.  
• Females of childbearing potential with irregular menstrual cycles must agree to have 
pregnancy tests weekly for the first 28 days of study participation and then every 

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14 days while taking pomalidomide, at study discontinuation, and at Days 14 and 28 
following the last dose of pomalidomide.  
• At each visit, the Investigator must confirm with the FCBP that she is continuing to 
use two reliable methods of birth control if not committing to complete abstinence, or 
confirm commitment to complete abstinence. 
• If a FCBP considers the need to change or to stop a method of contraception, the 
Investigator must be notified immediately. 
• Counseling about pregnancy precautions and the potential risks of fetal exposure 
must be conducted at a minimum of every 28 days.  
• If pregnancy or a positive pregnancy test does occur in a subject, pomalidomide must 
be immediately discontinued. 
• Pregnancy testing and counseling must be performed if a subject misses her period or 
if her pregnancy test or her menstrual bleeding is abnormal. Pomalidomide must be 
discontinued during this evaluation. 
• Females must agree to abstain from breastfeeding while taking pomalidomide and for 
at least 28 days after the last dose of pomalidomide. 
 
1.5.2.2 
Male Subjects 
• Must practice complete abstinence (True abstinence is acceptable when this is in line 
with the preferred and usual lifestyle of the subject. Periodic abstinence [eg calendar, 
ovulation, symptothermal or post-ovulation methods] and withdrawal are not 
acceptable methods of contraception.) or use a condom during sexual contact with a 
pregnant female or a FCBP while receiving pomalidomide, during dose interruptions 
and for at least 28 days after the last dose of pomalidomide, even if he has undergone 
a successful vasectomy. 
• Must not donate semen or sperm while receiving pomalidomide, during dose 
interruptions or for at least 28 days after the last dose of pomalidomide. 
• Counseling about pregnancy precautions and the potential risks of fetal exposure 
must be conducted at a minimum of every 28 days. 
• If pregnancy or a positive pregnancy test does occur in the partner of a male subject 
while taking pomalidomide, the Investigator must be notified immediately. 
 
1.5.3 
Additional Precautions 
• Subjects should be instructed to never give pomalidomide to another person. 
• Subjects should be instructed to return any unused capsules to the study doctor. 
• Subjects should not donate blood while receiving pomalidomide, during dose 
interruptions and for at least 28 days after the last dose of pomalidomide. 

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• No more than a 28-day pomalidomide supply may be dispensed with each cycle of 
pomalidomide.  
 
 

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APPENDIX E 
POMALIDOMIDE EDUCATION AND COUNSELING GUIDANCE 
DOCUMENT 
 
1. 
Pomalidomide Education and Counseling Guidance Document for Female Subjects 
To be completed prior to each dispensing of pomalidomide. 
Protocol Number: ____________________________________________ 
Subject Name (Print): __________________ DOB: _____/_____/_____ (dd/mmm/yyyy) 
Check one risk category: 
 FCBP (Female of childbearing potential): a female who: 1) has achieved menarche 
(first menstrual cycle) at some point, 2) has not undergone a hysterectomy (the 
surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of 
both ovaries) 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 during the preceding 24 consecutive months) 
 NOT FCBP 
 
1.1 
Female of Childbearing Potential: 
1. I have verified and counseled the subject regarding the following: 
 Potential risk of fetal exposure to pomalidomide: A teratogenic potential of 
pomalidomide in humans cannot be ruled out. If pomalidomide is taken during 
pregnancy, it may cause birth defects or death to any unborn baby. Females are 
advised to avoid pregnancy while taking pomalidomide. Females of childbearing 
potential must agree not to become pregnant while taking pomalidomide.  
 That the required pregnancy tests performed are negative. 
 The subject confirmed that she is using TWO reliable methods of birth control at the 
same time, or complete abstinence (True abstinence is acceptable when this is in line 
with the preferred and usual lifestyle of the subject. Periodic abstinence [eg calendar, 
ovulation, symptothermal or post-ovulation methods] and withdrawal are not 
acceptable methods of contraception.) from heterosexual contact (at least 28 days 
prior to receiving pomalidomide, while receiving pomalidomide, during dose 
interruptions and for at least 28 days after the last dose of pomalidomide).  
One highly effective method and one additional method of birth control must be used 
AT THE SAME TIME. The following are examples of highly effective and 
additional effective methods of contraception: 
− Examples of highly effective methods: 
o Intrauterine device (IUD) 
o Hormonal (birth control pills, injections, implants, levonorgestrel-releasing 
intrauterine system [IUS], medroxyprogesterone acetate depot injections, 
ovulation inhibitory progesterone-only pills [e.g. desogestrel]) 

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o Tubal ligation 
o Partner’s vasectomy 
− Examples of additional effective methods: 
o Male condom 
o Diaphragm 
o Cervical Cap 
 The subject confirmed that even if she has amenorrhea she must comply with advice 
on contraception. 
 Pregnancy tests before, during administration of pomalidomide and at the last dose of 
pomalidomide, even if the subject agrees not to have reproductive heterosexual 
contact. 
 Frequency of pregnancy tests to be done: 
− Two pregnancy tests will be performed prior to receiving pomalidomide, one 
within 10 to 14 days, and a second within 24 hours of the start of pomalidomide. 
− Every week during the first 28 days of this study and a pregnancy test every 
28 days while the subject is taking pomalidomide if menstrual cycles are regular.  
− Every week during the first 28 days of this study and a pregnancy test every 
14 days while the subject is taking pomalidomide if menstrual cycles are 
irregular. 
− If the subject missed a period or has unusual menstrual bleeding.   
− When the subject is discontinued from the study and at Day 28 after the last dose 
of pomalidomide if menstrual cycles are regular. If menstrual cycles are irregular, 
pregnancy tests will be done at discontinuation from the study and at Days 14 and 
28 after the last dose of pomalidomide. 
 The subject confirmed that she will stop taking pomalidomide immediately in the 
event of becoming pregnant and to call her study doctor as soon as possible.  
 The subject confirmed that she has not and will not breastfeed a baby while taking 
pomalidomide and for at least 28 days after the last dose of pomalidomide. 
 The subject has not and will never share pomalidomide with anyone else. 
 The subject has not and will not donate blood while taking pomalidomide, during 
dose interruptions and for at least 28 days after the last dose of pomalidomide. 
 The subject has not and will not break, chew, or open pomalidomide capsules at any 
point. 
 The subject confirmed that she will return unused pomalidomide capsules to the study 
doctor. 
2. I have provided the Pomalidomide Information Sheet to the subject. 
 

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1.2 
Female Not of Childbearing Potential (Natural Menopause for at Least 24 
Consecutive Months, a Hysterectomy, or Bilateral Oophorectomy): 
1. I have verified and counseled the subject regarding the following: 
 Potential risk of fetal exposure to pomalidomide: A teratogenic potential of 
pomalidomide in humans cannot be ruled out. If pomalidomide is taken during 
pregnancy, it may cause birth defects or death to any unborn baby. 
 The subject has not and will never share pomalidomide with anyone else. 
 The subject has not and will not donate blood while taking pomalidomide, during 
dose interruptions and for at least 28 days after the last dose of pomalidomide. 
 The subject has not and will not break, chew, or open pomalidomide capsules at any 
point. 
 The subject confirmed that she will return unused pomalidomide capsules to the study 
doctor. 
2. I have provided the Pomalidomide Information Sheet to the subject. 
Do Not Dispense Pomalidomide if: 
• The subject is pregnant. 
• No pregnancy tests were conducted for a FCBP. 
• The subject states she did not use TWO reliable methods of birth control (unless 
practicing complete abstinence from heterosexual contact) at least 28 days prior 
to receiving pomalidomide, while receiving pomalidomide and during dose 
interruptions. 
• The subject stated that she has or does not want to adhere to pregnancy 
precautions outlined within this Pregnancy Prevention Plan (PPP). 
 
Counselor Name (Print): ____________________ 
 
 
Counselor Signature: _______________________ 
Date: 
_____/_____/_____(dd/mmm/yyyy) 
 
**Maintain a copy of the Education and Counseling Guidance Document in the subject’s 
records.**

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2. 
Pomalidomide Education and Counseling Guidance Document for Male 
Subjects 
To be completed prior to each dispensing of pomalidomide. 
Protocol Number: ____________________________________________ 
Subject Name (Print): __________________ DOB: _____/_____/_____ (dd/mmm/yyyy) 
 
1. I have verified and counseled the subject regarding the following: 
 Potential risk of fetal exposure to pomalidomide: A teratogenic potential of 
pomalidomide in humans cannot be ruled out. If pomalidomide is taken during 
pregnancy, it may cause birth defects or death to any unborn baby. 
 The subject confirmed that he has practiced complete abstinence (True abstinence is 
acceptable when this is in line with the preferred and usual lifestyle of the subject. 
Periodic abstinence [eg calendar, ovulation, symptothermal or post-ovulation 
methods] and withdrawal are not acceptable methods of contraception.) or used a 
condom when engaging in sexual contact (including those who have had a 
vasectomy) with a pregnant female or FCBP, while taking pomalidomide, during 
dose interruptions and for at least 28 days after the last dose of pomalidomide. 
 The subject confirmed that he has not impregnated his female partner while in the 
study. 
 The subject confirmed that he will notify his study doctor if his female partner 
becomes pregnant and the female partner of a male subject taking pomalidomide 
confirmed that she will call her healthcare provider immediately if she becomes 
pregnant. 
 The subject has not and will never share pomalidomide with anyone else. 
 The subject confirmed that he has not donated and will not donate semen or sperm 
while taking pomalidomide or during dose interruptions and that he will not donate 
semen or sperm for at least 28 days after the last dose of pomalidomide. 
 The subject has not and will not donate blood while taking pomalidomide, during 
dose interruptions and for at least 28 days after the last dose of pomalidomide. 
 The subject has not and will not break, chew, or open pomalidomide capsules at any 
point. 
 The subject confirmed that he will return unused pomalidomide capsules to the study 
doctor. 
2. I have provided the Pomalidomide Information Sheet to the subject. 
Do Not Dispense Pomalidomide if: 
• The subject stated that he has or does not want to adhere to pregnancy 
precautions outlined within this PPP. 

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Counselor Name (Print): ____________________ 
 
 
Counselor Signature: _______________________  
Date: 
_____/_____/_____(dd/mmm/yyyy) 
 
**Maintain a copy of the Education and Counseling Guidance Document in the subject’s 
records.** 
 
 

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123 
APPENDIX F 
POMALIDOMIDE INFORMATION SHEET 
 
For subjects enrolled in clinical research studies  
Please read this Pomalidomide Information Sheet before you start taking pomalidomide and each 
time you get a new supply. This Pomalidomide Information Sheet does not take the place of an 
informed consent to participate in clinical research or talking to your study doctor or healthcare 
provider about your medical condition or your treatment.   
What is the most important information I should know about pomalidomide? 
1. Pomalidomide may cause birth defects (deformed babies) or death of an unborn 
baby. Pomalidomide is similar to the medicine thalidomide. It is known that thalidomide 
causes life-threatening birth defects. Pomalidomide has not been tested in pregnant 
women but may also cause birth defects. Pomalidomide was found to cause birth defects 
when tested in pregnant rats and rabbits. 
If you are a female who is able to become pregnant: 
• Do not take pomalidomide if you are pregnant or plan to become pregnant 
• You must practice complete abstinence from sexual contact with a male or use 
two reliable, separate forms of effective birth control at the same time:  
− for 28 days before starting pomalidomide 
− while taking pomalidomide  
− during breaks (dose interruptions) of pomalidomide  
− for at least 28 days after the last dose of pomalidomide  
• You must have pregnancy testing done at the following times: 
− within 10 to 14 days prior to the first dose of pomalidomide 
− 24 hours prior to the first dose of pomalidomide  
− weekly until completion of pomalidomide 
− if you have regular menstrual periods: every 28 days after the first month until 
completion of pomalidomide 
− if you have irregular menstrual periods: every 14 days after the first month until 
completion of pomalidomide 
− if you miss your period or have unusual menstrual bleeding 
− 28 days after the last dose of pomalidomide (14 and 28 days after the last dose if 
menstrual periods are irregular) 
• Stop taking pomalidomide if you become pregnant while taking pomalidomide 
− If you suspect you are pregnant at any time during the study, you must stop 
pomalidomide immediately and immediately inform your study doctor. Your 
study doctor will report all cases of pregnancy to the National Cancer Institute 

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124 
who will report the cases to the pharmaceutical collaborator, Celgene 
Corporation. 
• Do not breastfeed while taking pomalidomide and for at least 28 days after the 
last dose of pomalidomide 
• The study doctor will be able to advise you where to get additional advice on 
contraception. 
If you are a female not able to become pregnant: 
In order to ensure that an unborn baby is not exposed to pomalidomide, your study doctor 
will confirm that you are not able to become pregnant. 
If you are a male: 
The effect of pomalidomide on sperm development is not known and has not been 
studied. The risk to an unborn baby in females whose male partner is receiving 
pomalidomide is unknown at this time.  
• Male subjects (including those who have had a vasectomy) must practice complete 
abstinence or must use a condom during sexual contact with a pregnant female or a 
female that can become pregnant: 
− While you are taking pomalidomide  
− During breaks (dose interruptions) of pomalidomide  
− For at least 28 days after the last dose of pomalidomide   
• Male subjects should not donate sperm or semen while taking pomalidomide, 
during breaks (dose interruptions) and for at least 28 days after the last dose of 
pomalidomide.  
• If you suspect that your partner is pregnant any time during the study, you must 
immediately inform your study doctor. The study doctor will report all cases of 
pregnancy to the National Cancer Institute who will report the cases to the 
pharmaceutical collaborator, Celgene Corporation. Your partner should call 
their healthcare provider immediately if they become pregnant. 
2. All subjects: 
• Do not share pomalidomide with other people. It must be kept out of the reach of 
children and should never be given to any other person. 
• Do not donate blood while you take pomalidomide, during breaks (dose 
interruptions) and for at least 28 days after the last dose of pomalidomide.  
• Do not break, chew, or open pomalidomide capsules at any point. 
• You will get no more than a 28-day supply of pomalidomide at one time. 
• Return unused pomalidomide capsules to your study doctor. 
Additional information is provided in the informed consent form and you can ask your 
study doctor for more information. 

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125 
 
 
 

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126 
APPENDIX G 
CELGENE PREGNANCY PREVENTION AND COUNSELING 
PROGRAM SITE COUNSELOR IDENTIFICATION FORM 
• 
Please identify at least two (2) counselors and fax back to 888-314-2392 
• 
Use one form per counselor. 
• 
Identified counselors must be licensed healthcare professionals (e.g. RN, PA, RPh, PhD, LPN, CNP, 
or MD) and must not be the principal investigator.  
• 
If you have any questions, please email (coop ma@celgene.com) 
 
 
 
 
 
 
□
□
□
□
□
□
 
 
General Information 
Principal Investigator: 
Institution Name: 
Counselor Information 
CTEP person ID: 
CTEP site ID: 
First Name: 
Middle Initial:
Last Name: 
License Type: (circle one) MD PhD 
PA 
CNP 
RN 
LPN RPh 
Other: 
Email Address: 
Phone: 
Fax: 
Institution Street Address: 
City: 
State/Region: 
Zip/Post Code: 
Country: 
Which training will you require? 
Were you previously approved as a Counselor? 
No 
Adult 
Pediatric 
If no, please list all the protocols #(s), corresponding CTEPsiteID(s) and institution names(s) that you 
plan to provide counseling for: 
If yes, please list the protocols #(s), corresponding CTEPsiteID(s) and institution names(s) for protocols 
Celgene has already associated you with: 
Document A_Version 3.1 1/28/2015 
Page 1 of 1
Protocol#: 
CTEPsiteID 
Institution 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes (Previous training) 
Adult 
Pediatric 
 
Celgene 
Corporation 
Celgene Pregnancy Prevention & Counseling Program Site 
Counselor Identification Form 
NCI Protocol #: 

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APPENDIX H 
PATIENT’S MEDICATION DIARY FOR POMALIDOMIDE 
 
(See next page) 
 
 

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PATIENT’S MEDICATION DIARY – POMALIDOMIDE  
 
     Today’s date _______________________________ 
Agent_____Pomalidomide__________ 
     Patient Name_________________________ (initials acceptable) Patient Study ID _____________________ 
INSTRUCTIONS TO THE PATIENT: 
1. Complete one form for each month. 
2. You will take your dose of pomalidomide each day.  You will take one ___ capsule every day.  You should swallow the capsule 
whole.  Do not chew.  Do not break or open the capsules.  
3. If a dose of pomalidomide is missed, take the dose within 12 hours of when it is due.  If more than 12 hours have passed, the 
dose should be skipped.  Take the next dose at the usual time.  Do not take 2 doses to make up for the one missed.  If a patient 
vomits after taking pomalidomide, doses will not be made up and should be taken at the next scheduled dose. 
4. Record the date, the number of capsules of each size you took, and when you took them. 
5. If you have any comments or notice any side effects, please record them in the Comments column.   
6. Please return the forms to your physician when you go for your next appointment. 
 
Day 
 
Date 
What time was 
dose taken? 
# of capsules taken 
Comments 
_ mg 
 
 
1 
 
 
 
  
2 
 
 
 
  
3 
 
 
 
  
4 
 
 
 
  
5 
 
 
 
  
6 
 
 
 
  
7 
 
 
 
  
8 
 
 
 
  
9 
 
 
 
  
10 
 
 
 
  
11 
 
 
 
  
12 
 
 
 
  
13 
 
 
 
  
14 
 
 
 
  
15 
 
 
 
  
16 
 
 
 
  
17 
 
 
 
  
18 
 
 
 
  
19 
 
 
 
  
20 
 
 
 
  
21 
 
 
 
  
Physician’s Office will complete this section: 
1. 
Date patient started protocol treatment____________________________________________________________________ 
2. 
Date patient was removed from study_____________________________________________________________________ 
3. 
Patient’s planned total daily dose_____________________________________________________________ ___________ 
4. 
Total number of capsules taken this month (each size)___________________________________________________________ 
5. 
Physician/Nurse/Data Manager’s Signature ________________________________________________________________ 
 
    Patient’s signature:_________________________________________________________________________ 
 
 
CTEP-assigned Protocol 
#_10434__________ 
Local Protocol # ___________________ 

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129 
 
APPENDIX I 
CYTARABINE DRUG INFORMATION FOR HIGH DOSE 
CYTARABINE (HiDAC) CONSOLIDATION 
 
Below is a summary of information for cytarabine. For additional information, please refer to the 
prescribing information.  
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=681b5dc4-4fcf-4fab-ad78-
02cb9a4a5dd0&type=display 
 
Product description:  
Cytarabine Injection, an antineoplastic, is a sterile isotonic solution for intravenous and 
subcutaneous use. Cytarabine is cytotoxic to a wide variety of proliferating mammalian cells in 
culture. It exhibits cell phase specificity, primarily killing cells undergoing DNA synthesis (S-
phase) and under certain conditions blocking the progression of cells from the G1 phase to the S-
phase. Although the mechanism of action is not completely understood, it appears that cytarabine 
acts through the inhibition of DNA polymerase. 
 
Cytarabine Injection, an antineoplastic, is a sterile isotonic solution for intravenous and 
subcutaneous use, which contains no preservative and is available in 20 mg/mL (1000 mg/50 
mL) Pharmacy Bulk Package. 
 
A Pharmacy Bulk Package is a container of a sterile preparation for parenteral use that contains 
many single doses. The contents are intended for use in a pharmacy admixture program and are 
restricted to the preparation of admixtures for intravenous infusion. 
 
Each mL contains 20 mg cytarabine, USP and the following inactive ingredients: sodium 
chloride 0.68% and Water for Injection q.s. When necessary, the pH is adjusted with 
hydrochloric acid and/or sodium hydroxide to a target pH of 7.4. Each vial contains 
approximately 5.82 mEq sodium. 
 
Agent Supply: 
Cytarabine will be commercially supplied. 
 
Solution preparation  
Please refer to the package insert. 
 
Route of administration:  
IV 
 
Dosage and Administration 
In patients who develop cardiomyopathy or who exceed lifetime anthracycline dose of > 430 
mg/m2 (or >280 mg/m2 with prior mediastinal radiation) or have any other contraindications to 
daunorubicin and cytarabine liposome consolidation, moderate-high dose (1-3 g/m2 IV Q12 
hours days 1, 3 and 5) cytarabine can be used in place of daunorubicin and cytarabine liposome 
for consolidation. 

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Storage  
Store at 20°C to 25°C (68°F to 77°F) [USP Controlled Room Temperature]. 
 
Stability 
Chemical stability studies were performed by a stability indicating HPLC assay on cytarabine 
injection in infusion solutions. These studies showed that when cytarabine injection was diluted 
with Water for Injection, 5% Dextrose Injection or Sodium Chloride Injection, in both glass and 
plastic infusion bags, 97-100% of the cytarabine was present after 8 days storage at room 
temperature.   
 
Adverse Events: 
Expected Reactions: Because cytarabine is a bone marrow suppressant, anemia, leukopenia, 
thrombocytopenia, megaloblastosis and reduced reticulocytes can be expected as a result of 
administration with cytarabine. The severity of these reactions are dose and schedule dependent. 
Cellular changes in the morphology of bone marrow and peripheral smears can be expected. 
Infectious Complications: Infection: Viral, bacterial, fungal, parasitic, or saprophytic 
infections, in any location in the body may be associated with the use of cytarabine alone or in 
combination with other immunosuppressive agents following immunosuppressant doses that 
affect cellular or humoral immunity. These infections may be mild, but can be severe and at 
times fatal. 
The Cytarabine (Ara-C) Syndrome: A cytarabine syndrome has been described by 
Castleberry. It is characterized by fever, myalgia, bone pain, occasionally chest pain, 
maculopapular rash, conjunctivitis and malaise. It usually occurs 6-12 hours following drug 
administration. Corticosteroids have been shown to be beneficial in treating or preventing this 
syndrome. If the symptoms of the syndrome are deemed treatable, corticosteroids should be 
contemplated as well as continuation of therapy with Cytarabine Injection. 
 
Most Frequent Adverse Reactions: Anorexia, hepatic dysfunction, nausea, fever, vomiting, 
rash, diarrhea, thrombophlebitis, oral and anal inflammation or ulceration, bleeding (all sites). 
Nausea and vomiting are most frequent following rapid intravenous injection. 
 
Less Frequent Adverse Reactions: Sepsis, abdominal pain, pneumonia, freckling, cellulitis at 
injection site, jaundice, skin ulceration, conjunctivitis (may occur with rash), urinary retention, 
dizziness, renal dysfunction, alopecia, neuritis, anaphylaxis, neural toxicity, allergic edema, sore 
throat, pruritus, esophageal ulceration, shortness of breath, esophagitis, urticaria, chest pain, 
pericarditis, headache, bowel necrosis, pancreatitis, sinus bradycardia. 
 
Handling and Disposal:  
Procedures for proper handling and disposal of anti-cancer drugs should be considered. Several 
guidelines on this patient have been published. There is no general agreement that all of the 
procedures recommended in the guidelines are necessary or appropriate. Dispose of remaining 
drug per institutional guidelines. 
 
 

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APPENDIX J 
RESPONSE CRITERIA FOR AML 
 
Category 
Definition 
Response 
CR without minimal residual(CRMRD-) 
If studied pretreatment, CR with 
negativity for a genetic marker by RT-
qPCR, or CR with negativity by MFC 
Complete remission (CR) 
Bone marrow blasts ,< 5%; absence of 
circulating blasts and blasts with Auer 
rods; absence of extramedullary disease; 
ANC ≥1.0 x 109/L (1000/mL); platelet 
count ≥100 x 109/L (100 000/mL) 
CR with incomplete hematologic recovery 
(CRi) 
All CR criteria except for residual 
neutropenia (< 1.0 x 109/L [1000/mL]) or 
thrombocytopenia (< 100 x 109/L  
 
Morphologic leukemia-free state (MLFS) 
Bone marrow blasts < 5%; absence of 
blasts with Auer rods; absence of 
extramedullary disease; no hematologic 
recovery required 
Partial remission (PR) 
All hematologic criteria of CR; decrease 
of bone marrow blast percentage to 5% to 
25%; and decrease of pretreatment bone 
marrow blast percentage by at least 50% 
Treatment failure 
Primary refractory disease 
No CR or CRi after 1-2 courses of 
intensive induction treatment; excluding 
patients with death in aplasia or death due 
to indeterminate cause 
Relapsed Disease (after CR, CRh, or CRi) 
Bone marrow blasts >5%; or 
reappearance of blasts in the blood in at 
least 2 peripheral blood samples at least 1 
week apart; or development of 
extramedullary disease 
(Dohner et al., 2022) 
 
 

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APPENDIX K 
REQUISITION FORM: MOLECULAR GENETICS 
LABORATORY, UNC HOSPITALS 
 
 
Use only for: NCI 10434: Randomized Phase 2 Study of daunorubicin and cytarabine liposome 
+ Pomalidomide versus daunorubicin and cytarabine liposome in Newly Diagnosed AML with 
MDS-Related Changes. 
Facility Name (Sending Site):_____________________________ 
 
Facility Address: ________________________ City/State/Zip:_______________________ 
 
Phone number: ________________ 
 
Form Completed By: ________________________ 
 
Specimen ID: _________________   (Write the ID or place labels with specimen ID only) 
 
Specimen Type: 
1. Peripheral Blood – EDTA ; Number of Tubes: _______ 
2. Bone marrow Aspirate – EDTA; Number of Tubes: _______ 
3. Bone marrow Aspirate – Sodium Heparin; Number of Tubes: _______ 
 
Collection Date & Time_____________ 
 
1. Label each sample with the following information:  
• Specimen ID 
• Date and time of sample collection; and  
• Initials of person responsible for collection 
2.  Packaging the sample:  
 
a. Place absorbent material around the labeled specimen container, and insert into a 
watertight container. Paperwork should be enclosed in a separate plastic bag 
accompanying the specimen.  
 
b. Place the container and the paperwork (this requisition) in a sturdy outer container 
along with a cold pack. Add enough cold packs to the container for the tubes to 
arrive cold at UNC.       DO NOT SHIP ON DRY ICE   
 
c. Total number of EDTA Tubes shipped: _________    Date Shipped: 
 
 
d. Seal the shipping container with waterproof tape. Mail the package promptly by 
an express service (preferably FedEx) to the following address. 
 
Attn: Molecular Genetics Lab 
McLendon Clinical Laboratories  

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133 
Outreach Services, 1st floor, East Wing  
UNC Hospitals  
Chapel Hill, NC - 27514  
Phone: (984) 974-1825 
 
 
e. The specimens must be shipped for arrival to the laboratory on Monday through 
Friday. Molecular Genetics laboratory is closed over the weekends, and 
specimens cannot be accepted on weekends. 
 
a. Please send a ‘heads-up’ email with the NCI 10434 Specimen ID, and shipment 
tracking to the UNC staff email addresses below to ensure receipt: 
Rachana.kshatriya@unchealth.unc.edu and wendy.thompson@unchealth.unc.edu 
 
Questions? Call UNC Molecular Genetics Laboratory at (984) 974-1825  
UNC use only: receipt date______________ 
time_______________MLM#_____________initials____________ 
 
 

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APPENDIX L 
TUMOR PROCUREMENT FACILITY SPECIMENT SHIPPING 
INSTRUCTIONS 
Shipping instructions for AMBIENT samples: 
• Include the appropriate submission form with each sample.  
• For tissue slides please also include the corresponding pathology report(s).  Remove 
name, MRN or any other PHI from the report.  Write the initials, study number 
(NCI10434) and sequence number on the pathology report. 
• Ship overnight.  These samples must NOT be shipped on dry ice. 
• Samples may only be sent Monday through Thursday.  DO NOT ship on Friday, Saturday, 
Sunday, or the day before a holiday. Allow ample time for delivery.  Any questions 
regarding holiday schedules may be addressed to the appropriate lab contact(s) on the 
specimen submission forms.   
• Please notify CPO PM and UNC-TPF of an incoming shipment by e-mailing a copy of the 
submission form. 
 
Shipping instructions for Refrigerated (2–8oC) samples: 
• Include the appropriate submission form with each sample.  
• For fresh tissue please also include the corresponding pathology report(s).  Remove 
name, MRN or any other PHI from the report.  Write the initials, study number 
(NCI10434) and sequence number on the pathology report. 
• Ship overnight.  These samples must NOT be shipped on dry ice; send with gel packs 
that will maintain the fresh tissue sample at refrigerator temperatures (2 – 80C)   
• Samples may only be sent Monday through Thursday.  DO NOT ship on Friday, Saturday, 
Sunday, or the day before a holiday. Allow ample time for delivery.   
• Please notify CPO PM and UNC-TPF of an incoming shipment by e-mailing a copy of the 
appropriate submission form. 
 
Shipping instructions for FROZEN samples: 
• Please ship frozen PBMC, plasma, and tissue as they are collected and processed. Do not 
wait to batch ship. 
• Samples may only be sent Monday through Wednesday.  DO NOT ship on Thursday, 
Friday, Saturday, Sunday, or the day before a holiday. Allow ample time for delivery.   
• Package samples in an insulated Styrofoam box with plenty of dry ice. 
• Place Styrofoam box within another box (e.g., cardboard, wooden, plastic).  
• Complete and affix Dry Ice label to the outside of the package. 
• Please send samples by courier that guarantees overnight service. 
• Please notify the CPO PM and UNC-TPF of an incoming shipment by e-mailing a copy of 
the appropriate submission form. 
 
IATA PACKING INSTRUCTIONS 
 

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135 
 
• http://www.iata.org/whatwedo/cargo/dangerous_goods/Documents/DGR52_PI650_EN
.pdf 
 
Multicenter Site Shipping of Specimens 
• Multicenter Sites will ship all specimens to: 
Tissue Procurement Facility 
108 MacNider Building 
333 South Columbia St 
Chapel Hill, NC 27599 
 
(All specimens will be shipped as appropriate to the specimen type as outlined above.) 
 
UNC-TPF Receipt of Specimens 
• Upon Receipt, UNC-TPF will notify the sending site and UNC project manager of the 
receipt and condition of all specimens. 
• UNC-TPF Storage and Distribution of Specimens 
• UNC-TPF will store all frozen specimens at -70 or below. 
• All whole blood shipped ambient will be processed to PBMC/Plasma and stored as 
above. 
• All tissue specimens will be stored in a desiccator. 
• All specimens will be stored at the UNC-TPF biorepository until requested for release to 
the lab(s) of analysis. 
 
 
 

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APPENDIX M 
CRYOPRESERVATION OF PBMC’S FROM FRESH PB AND BM 
SAMPLES 
 
Purpose:  
PBMCs (peripheral blood mononuclear cells) are cryopreserved for later separation for Aiolos 
expression and lymphocyte subsets analysis. 
 
Supplies: 
• (2) 10mL green top Heparin tubes 
• Ficoll Plaque Premium GE ficoll-paque 17-5442-03  
• FBS (Fetal Bovine Serum) SH3008803HI Heat Inactivated FBS 
• PBS  Hyclone DPBS Modified w/o calcium w/o magnesium 
• Wide 1000ul Pipette tips – Finntip 9405163 
• Conical Tubes 50ml 
• Cryovial for storing isolated mononuclear cells (For sample quality and quantity please use 
externally threaded cryovials, such as Fisherbrand 10-500-26) 
• Mr. Frosty  freezing chamber 
 
Specimen Process: 
1. Warm-up the Ficoll medium to room temperature (RT) protected from light, and 
mix the medium by inverting the bottle gently.  
2. Aseptically transfer 15-20ml of Ficoll medium to a 50ml conical tube 
3. Carefully layer the blood (max 25 ml per tube) on top of the Ficoll, using a 
serological pipette. Close the tubes with the screw-cap.  
4. Centrifuge 30 minutes at 400 x g at 20oC in a swinging bucket rotor without brake. 
5. After centrifugation, the sequence of layers occurs as follows (from top to 
bottom): 
 
a. Plasma 
b. Enriched fraction (interphase of lymphocytes or 
mononuclear cells) 
c. Ficoll medium 
d. Ficoll medium 
e. Pellet (erythrocytes and granulocytes) 
6. Remove the plasma layer fraction up to a minimum 
remnant of 5 to 10 mm above the interphase. This helps to prevent contamination 
of the enriched cells with platelets. 
7. Harvest the enriched cell fraction (lymphocytes or mononuclear cells) by means 
of a Pasteur pipette and transfer into a new 50mL Falcon tube. 
8. Add PBS to the cells in the conical tube tube to a total volume of 50mL, and 
centrifuge for 10 minutes at room temperature (18-25oC) at a speed sufficient to 

NCI Protocol #:  10434 
Version Date:  March 3, 2025 
137 
sediment the cells without damaging cells. i.e. 400 x g. (Washing removes Ficoll 
medium and reduces the percentage of platelets).  
9. Remove supernatant, and add enough PBS to the tube for cell count. 
10. Count cell numbers. Expect 1 x 106 cells/ml of whole blood.   
11. Prepare a minimum of 5-10 million cells in each cryovial in 1.8 mls final volume. 
12. Spin down the specimens at 400 x g and add freezing medium (90% FBS and 10% 
DMSO) to the cells. Mix it with pipet up and down 4 times gently. Avoid making 
bubbles. 
13. Each cryovial tube should be marked on a temperature-resistant label with the 
following mandatory information: 
- 
Study Number, Study Site, and Subject Number (1522UNC-101, 1522JH-102) 
- 
Time Point 
- 
Date Sample Drawn and Processed 
- 
Sample Type (PBMC) 
- 
Cell Number (PBMC) 
- 
Freezing Volume (PBMC) 
14. The vials should be put in a pre-chilled slow freezing container Mr. Frosty to 
guarantee that the temperature drops 1 degree/minute, and put it in -80oC freezer 
for 18-72 hours prior to storing them in LN2 unit. 
15. All vials should be transferred to liquid nitrogen. 
16. TPF should use their database to track the aliquots. 
 
 
 
Tissue Procurement Facility BMMNC from Bone Marrow Specimens 
 
Supplies: 
• 100 u strainer 
• (2-4) 10MmL green top Heparin tubes 
• Ficoll Plaque Premium GE ficoll-paque 17-5442-03  
• FBS (Fetal Bovine Serum) SH3008803HI Heat Inactivated FBS 
• PBS  Hyclone DPBS Modified w/o calcium w/o magnesium 
• Wide 1000ul Pipette tips – Finntip 9405163 
• Conical Tubes 50ml 
• 100 uM filter BD Falcon Cell Strainer 352360 
• Cryovial for storing isolated mononuclear cells (For sample quality and quantity please use 
externally threaded cryovials, such as Fisherbrand 10-500-26) 
• Mr. Frosty  freezing chamber 
 
Specimen Process: 
1. Warm-up the Ficoll medium to room temperature (RT) protected from light, and mix 
the medium by inverting the bottle gently.  
2. Aseptically transfer 15-20ml of Ficoll medium to a 50ml conical tube 

NCI Protocol #:  10434 
Version Date:  March 3, 2025 
138 
3. Carefully layer the bone marrow aspirate (max 25 ml per tube) on top of the Ficoll, 
using a serological pipette. Close the tubes with the screw-cap.  
4. Centrifuge 30 minutes at 400 x g at 20oC in a swinging bucket rotor without brake. 
5. After centrifugation, the sequence of layers occurs as follows (from top to bottom): 
a. Plasma 
b. Enriched fraction (interphase of 
lymphocytes or mononuclear cells) 
c. Ficoll medium 
d. Ficoll medium 
e. Pellet (erythrocytes and granulocytes) 
 
 
 
 
6. Remove the plasma layer fraction up to a minimum 
remnant of 5 to 10 mm above the interphase. This helps to prevent contamination of 
the enriched cells with platelets. 
7. Harvest the enriched cell fraction (lymphocytes or mononuclear cells) by means of a 
Pasteur pipette and filter it through a 100u cell strainer into a new 50mL conical tube.  
8. Add PBS to the cells in the centrifuge tube to a total volume of 50mL, and centrifuge 
for 10 minutes at room temperature (18-25oC) at a speed sufficient to sediment the 
cells without damaging cells. i.e. 400 x g. (Washing removes Ficoll medium and 
reduces the percentage of platelets).  
9. Remove supernatant, and add enough PBS to the tube for cell count. 
10. Count cell numbers. Expect a large number of cells that are AML tumor blasts, 
nucleated red blood cells, myeloid cells, and lymphocytes.     
11. Prepare a minimum of 10 - 15 million cells in each cryovial in 1.8 mls final volume. 
12. Spin down the specimens at 400 x g and add freezing medium (90% FBS and 10% 
DMSO) to the cells. Mix it with pipet up and down 4 times gently. Avoid making 
bubbles. 
13. Each cryovial tube should be marked on a temperature-resistant label with the 
following mandatory information: 
- 
 Study Number, Study Site, and Subject Number (1522UNC-101, 1522JH-102) 
- 
Time Point 
- 
Date Sample Drawn and Processed 
- 
Sample Type (BMMNC) 
- 
Cell Number (BMMNC) 
14. The vials should be put in a pre-chilled slow freezing container Mr. Frosty to 
guarantee that the temperature drops 1 degree/minute, and put it in -80oC freezer 
for 18-72 hours prior to storing them in LN2 unit. 
15. All vials should be transferred to liquid nitrogen. 
16. TPF should use their database to track the aliquots.