A Phase 1b/2 Study of Hu5F9-G4 (Magrolimab) in Combination With Mogamulizumab in Relapsed/Refractory Treated T-Cell Lymphoma
Phase: PHASE1
Conditions: Mycosis Fungoides, Recurrent Mycosis Fungoides, Recurrent Mycosis Fungoides and Sezary Syndrome, Recurrent Sezary Syndrome, Refractory Mycosis Fungoides, Refractory Mycosis Fungoides and Sezary Syndrome, Refractory Sezary Syndrome, Sezary Syndrome, Stage IB Mycosis Fungoides and Sezary Syndrome AJCC v8, Stage II Mycosis Fungoides and Sezary Syndrome AJCC v8, Stage III Mycosis Fungoides and Sezary Syndrome AJCC v8, Stage IV Mycosis Fungoides and Sezary Syndrome AJCC v8
Sponsor: National Cancer Institute (NCI)

i 
To:  
CTEP Protocol and Information Office  
From: Michael Khodadoust, M.D., Ph.D. 
Date:  September 5, 2023 
Re: 
Protocol # 10384: “A Phase 1b/2 Study of Hu5F9-G4 (magrolimab) in Combination with 
Mogamulizumab in Relapsed/Refractory Treated T-Cell Lymphoma” 
 
 
SUMMARY OF CHANGES – Protocol 
 
 
Section 
Comments 
Face Page 
Updated version date to September 5, 2023 
TOC 
Updated page numbers. 
Schema, 
2.4.4, 6.1 
The phase 1b portion of the study has been completed and the RP2D has been 
defined as Level 1 (30mg/kg magrolimab).  Relevant sections of the protocol 
have been updated to define the phase 2 dose.   
3.1, 6.6 
The eligibility has been changed to include patients with large cell 
transformation in the July 31, 2023 version. This introduces an increased 
likelihood of patients with aggressive disease being included in the study.  
This amendment was not approved by the CTEP PRC, as patients with LCT may 
respond differently to the Mogamulizumab backbone and the combination, therefore 
confounding the analysis of primary endpoint of the trial.     
 
We understand there is concern with accrual for this trial.   We will be happy to 
discuss with the investigator other ways the protocol might be modified to improve 
enrollment.   
 
PI Response:  The eligibility has been updated back to the original language 
without LCT patients.  
11 
Clarification of the below footnotes were done.  
g. EOT scans are not required if last scans were done within 28 days. 
h. maximum number of cycles is 12 
l. added RBC genetyping to list 
4.1 
Please delete the language within this section and replace it with the 
current CTEP protocol template language.  
 
Investigator and Research Associate Registration with CTEP 
Food and Drug Administration (FDA) regulations require sponsors to select 
qualified investigators.  National Cancer Institute (NCI) policy requires all 
individuals contributing to NCI-sponsored trials to register with their 
qualifications and credentials and to renew their registration annually.  To 

NCI Protocol #:  10384 
Version Date:  September 5, 2023 
 
iii 
Section 
Comments 
• Assignment of the Clinical Investigator (CI) task 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.  
 
Refer to the NCI RCR page on the CTEP website for additional information.  
For questions, please contact the RCR Help Desk by email at 
RCRHelpDesk@nih.gov 
PI Response: Done 
4.2 
 
Please revise within this section as shown to reflect the current CTEP 
protocol template language. 
In addition, the Site-Protocol Principal Investigator (PI) (i.e., the investigator 
on the IRB/REB approval) must meet the following criteria to complete for 
the site to be able to have an Approved status following processing of the 
IRB/REB approval record to be completed: 
• Holds Have an active CTEP status; 
• Active Have an 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, be 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 Have the appropriate CTEP registration type for the protocol.  
 
Additional Requirements 
Additional site requirements to obtain an approved site registration status 
include: 
• An active Federal Wide 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 

NCI Protocol #:  10384 
Version Date:  September 5, 2023 
 
iv 
Section 
Comments 
Compliance with all applicable protocol-specific requirements (PSRs). 
PI Response: Done 
4.2.1 
Please revise within this section as shown to reflect the current CTEP 
protocol template language. 
 
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: 
• 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-CA043 and protocol number 10384. 
Click on Documents, Protocol Related Documents, and use the Document 
Type filter and select Site Registration, to download and complete the forms 
provided.  (Note:  For sites under the CIRB, IRB data will load automatically 
to the CTSU.)  
PI Response:  Done 
4.2.2 
Please revise within this section as shown to reflect the current CTEP 
protocol template language. 
• 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. Users are strongly encouraged to take a 
refresher of the training if they have not entered specimen data for 
an extended period of time 
o This training will need to be completed before the first patient 
enrollment at a given site. 
Please contact STS Support at Theradex for the training 

NCI Protocol #:  10384 
Version Date:  September 5, 2023 
 
v 
Section 
Comments 
(STS.Support@theradex.com Theradex phone: 609 799 7580). 
PI Response:  Done 
4.2.2 
Please revise within this section as shown to reflect the current CTEP 
protocol template language. 
• 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. Users are strongly encouraged to take a 
refresher of the training if they have not entered specimen data for 
an extended period of time 
o This training will need to be completed before the first patient 
enrollment at a given site. 
Please contact STS Support at Theradex for the training 
(STS.Support@theradex.com Theradex phone: 609 799 7580). 
PI Response:  Done 
4.2.3 
Please revise as shown, to reflect the updated CTEP protocol template 
language. 
Each site must complete a protocol-specific Delegation of Tasks Log (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 to 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 describe DTL task assignments, CI signature, and CTEP 
registration requirements, as well as include a Master Task List. 
PI Response:  Done 

NCI Protocol #:  10384 
Version Date:  September 5, 2023 
 
vi 
Section 
Comments 
4.2.4 
Please revise within this section as shown, to reflect the updated CTEP 
protocol template language. 
Site’s registration status may be verified on the CTSU members’ website. 
PI Response:  Done 
4.3.1 
Please revise within this section as shown, to reflect the updated CTEP 
protocol template language. 
Patient enrollment for this study will be facilitated using the Slot Reservation 
System in conjunction with the registration system patient enrollment in 
OPEN. Prior to discussing protocol entry with the patient, all site staff must 
use the CTSU OPEN 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. 
PI Response:  Done 
13.2 
 
Please revise as shown, to reflect the updated CTEP protocol template 
language. 
Medidata Rave is a the 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.  
Requirements to access Rave via iMedidata: 
• 
A valid account, and  
• 
Active CTEP registration with the credentials necessary to access 
secure NCI/CTSU IT systems, 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: 
• 
Rave CRA or Rave CRA (Lab Admin) role must have a minimum of 
an Associate Plus (AP) registration type; 
• 
Rave Investigator role must be registered as a Non-Physician 
Investigator (NPIVR) or Investigator (IVR); and 
• 
To hold Rave Read Only or Rave SLA role site staff must have at a 
minimum hold an Associate (A) registration type. 
Refer to https://ctep.cancer.gov/investigatorResources/default.htm for 
registration types and documentation required. 
If the study has a Delegation of Tasks Log (DTL), individuals requiring write 
access to Rave must also be assigned the appropriate Rave tasks on the DTL. 

NCI Protocol #:  10384 
Version Date:  September 5, 2023 
 
vii 
Section 
Comments 
Upon initial site registration approval for the study in Regulatory Supposrt 
System (RSS) the Regulatory application, 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 who have not previously activated their iMedidata/Rave 
account at the time of initial site registration approval for the study in RSS the 
Regulatory application 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 email at ctsucontact@westat.com.   
PI Response:  Done 
13.3 
Please delete the language within this section and replace it with the 
current CTEP protocol template language. Instructions to the protocol 
author appear in blue italics and should not be added to the protocol 
document. 
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.  Site staff should review the DQP modules on a 

NCI Protocol #:  10384 
Version Date:  September 5, 2023 
 
viii 
Section 
Comments 
regular basis to manage specified queries and delinquent forms. 
 
The DQP is accessible by site staff who are rostered to a site and have 
access to the CTSU website.  Staff who have Rave study access can 
access the Rave study data via direct links available on the DQP 
modules. 
 
CTSU Delinquency Notification emails are sent to primary contacts at 
sites twice a month. These notifications serve as alerts that queries 
and/or delinquent forms require site review, providing a summary 
count of queries and delinquent forms for each Rave study that a site 
is participating in. Additional site staff can subscribe and unsubscribe 
to these notifications using the CTSU Report and Information 
Subscription Portal on the CTSU members’ website. 
 
To learn more about DQP use and access, click on the Help Topics 
button displayed on the Rave Home, DQP Queries, DQP Delinquent 
Forms, DQP Form Status, and DQP Reports modules. 
 
Include the following paragraph only if study is not using the Calendaring 
functionality in Rave; otherwise, delete. 
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. 
PI Response:  Done 
10.3.1 
Please revise within this section as shown, to reflect the updated CTEP 
protocol template language. 
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 Ddays after the Last 
Administration last administration of the Investigational 
Agent/Intervention investigational study 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.  

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Section 
Comments 
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 evaluation by completing the Expedited Reporting Evaluation form (i.e., 
checking the box Send All AEs for Evaluation and save the 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. 
PI Response:  Done 
9.2 
Please insert an “International Planned Enrollment Report” table for the 
treatment phase of the study since Princess Margaret Cancer Center is listed 
as a participant. 
PI Response:  This has been inserted. 
 
 

1 
NCI Protocol #: 
10384 
 
Local Protocol #: 
PhII-203 
 
ClinicalTrials.gov Identifier:  NCT04541017 
 
TITLE:  A Phase 1b/2 Study of Hu5F9-G4 (magrolimab) in Combination with Mogamulizumab 
in Relapsed/Refractory Treated T- cell Lymphoma  
 
Corresponding Organization: LAO-CA043 / City of Hope Comprehensive Cancer Center 
LAO  
 
Principal Investigator: 
Michael Khodadoust 
Stanford Cancer Institute 
300 Pasteur Drive, 
S140A Grant Building 
Stanford, CA 94305, USA 
650-497-4096 
650-736-1454 (fax) 
mkhodado@stanford.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 
EDDOP / Early Drug Development Opportunity Program 
 
Statistician: 
Paul Frankel, PhD 
City of Hope 
1500 E. Duarte Road 
Duarte, CA 91010 
626-218-5265 
pfrankel@coh.org  
 
 
 

NCI Protocol #:  10384 
Version Date:  September 5, 2023 
 
2 
Study Coordinator: 
 
 
Stella Khoo 
City of Hope 
1500 E. Duarte Rd. 
Duarte, CA 91010 
Telephone: 626-218-0094 
Fax: 626-218-8654 
ccc@coh.org  
 
NCI-Supplied Agent:  Hu5F9-G4 (magrolimab) (NSC 809249)  
Other Agent(s):  KW-0761 (mogamulizumab) (NSC 791064) 
 
IND #:  
 
IND Sponsor:  DCTD, NCI 
 
Protocol Type / Version # / Version Date: 
 
Original / May 7, 2020 
 
 
 
 
 
Revision 1 / July 6, 2020 
 
 
 
 
 
Revision 2 / August 7, 2020 
 
 
 
 
 
Revision 3a / September 25, 2020 
 
 
 
 
 
Revision 3b / October 5, 2020 
 
 
 
 
 
Revision 4 / October 28, 2020 
 
 
 
 
 
Revision 5 / December 18, 2020 
 
 
 
 
 
Revision 6 / November 4, 2021 
 
 
 
 
 
Revision 7 / January 24, 2022 
 
 
 
 
 
Revision 8 / July 14, 2022 
 
 
 
 
 
Revision 9 / August 9, 2022 
 
 
 
 
 
Revision 10 / May 30, 2023 
 
 
 
 
 
Revision 11 / July 31, 2023 (disapproved) 
 
 
 
 
 
Revision 12 / September 5, 2023 
 
 

NCI Protocol #:  10384 
Version Date:  September 5, 2023 
 
3 
SCHEMA 
 
 
 
Figure 1: Overall Trial Schema 
 
 
 
Figure 2: Treatment, Response Assessment, and Correlative Sampling Schedule for Phase 1b 
and Phase 2 
DLT = dose limiting toxicity; q12 = every 12 weeks 
 

NCI Protocol #:  10384 
Version Date:  September 5, 2023 
 
4 
 
Figure 3: Phase 1b Dose De-escalation Design 
DLT = dose limiting toxicity; DL = dose level 
 
Table 1: Dose De-escalation Schedule for Phase 1b 
Dose De-escalation Schedule 
Dose Level 
Dose 
Cycle Length 
Hu5F9-G4 
(Magrolimab) 
Mogamulizumab 
Level 1 (starting dose 
level) 
1 mg/kg IV priming 
dose; Then 30 mg/kg 
IV weekly in Cycles 
1 & 2 followed by 
Q2W in ≥ Cycle 3.  
Give before 
mogamulizumab. 
1 mg/kg IV (weekly 
for first cycle then 
Q2W starting cycle 2) 
28 Days 
Level -1 
1 mg/kg IV priming 
dose; Then 20 mg/kg 
IV weekly in Cycles 
1 & 2 followed by 
Q2W in ≥ Cycle 3.  
Give before 
mogamulizumab. 
1 mg/kg IV (weekly 
for first cycle then 
Q2W starting cycle 2) 
28 Days 
Q2W = Every 2 weeks, IV = Intravenous 
 
Phase 2 Design: 
The phase 1b portion has been completed and the phase 2 portion of the protocol is now open..  
There was one DLT identified in the phase 1b portion of the trial with 6 patients treated at dose 
Level 1.  Therefore, the recommended phase 2 dose (RP2D) was established as Level 1 
(30mg/kg magrolimab starting cycle 1). The phase 2 portion will be a two-arm, randomized, 
open-label design.  This cohort will seek to determine whether Hu5F9-G4 (magrolimab) plus 

NCI Protocol #:  10384 
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5 
mogamulizumab will have improved efficacy as compared to mogamulizumab alone.  We will 
enroll 82 patients with relapsed or refractory mycosis fungoides (MF) / Sézary Syndrome (SS).  
Patients will be randomized 1:1 to either Hu5F9-G4 (magrolimab) plus mogamulizumab or 
mogamulizumab alone.  Randomization will be stratified by 2 characteristics:  1) Disease type 
(MF vs SS) and 2) Stage (1B-2A vs 2B-IV).  To encourage accrual and to better assess the added 
effect of Hu5F9-G4 (magrolimab), the trial will allow for one-way crossover from the 
mogamulizumab only arm to the combination arm.  Crossover will be allowed for patients with 
progressive disease or stable disease lasting 6 months.  While not typically a criterion for 
crossover in other cancers, prolonged stable disease has not been an acceptable outcome for this 
patient population due to the presence of symptoms associated with ongoing disease. 
 
 

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6 
TABLE OF CONTENTS 
SCHEMA 
......................................................................................................................3 
1. 
OBJECTIVES ......................................................................................................................9 
1.1 
Primary Objectives ...................................................................................................9 
1.2 
Secondary Objectives ...............................................................................................9 
1.3 
Exploratory Objectives ............................................................................................9 
2. 
BACKGROUND .................................................................................................................9 
2.1 
Study Diseases .........................................................................................................9 
2.2 
CTEP IND Agent ...................................................................................................11 
2.3 
Other Agent ............................................................................................................15 
2.4 
Rationale ................................................................................................................16 
2.5 
Correlative Studies Background ............................................................................20 
3. 
PATIENT SELECTION ....................................................................................................24 
3.1 
Eligibility Criteria ..................................................................................................24 
3.2 
Exclusion Criteria ..................................................................................................26 
3.3 
Inclusion of Women and Minorities ......................................................................28 
4. 
REGISTRATION PROCEDURES ...................................................................................28 
4.1 
Investigator and Research Associate Registration with CTEP ..............................28 
4.2 
Site Registration .....................................................................................................29 
4.3 
Patient Registration ................................................................................................32 
4.4 
General Guidelines .................................................................................................34 
5. 
BIOMARKER, CORRELATIVE, AND SPECIAL STUDIES ........................................34 
5.1 
Summary Table for Specimen Collection ..............................................................34 
5.2 
Specimen Procurement Kits and Scheduling .........................................................36 
5.3 
Specimen Tracking System Instructions ................................................................36 
5.4 
Specimen Collection ..............................................................................................40 
5.5 
Shipping Specimens from Clinical Site to the EET Biobank ................................42 
5.6 
Biomarker Plan ......................................................................................................45 
5.7 
Integrated Correlative Studies ................................................................................51 
5.8 
Exploratory/Ancillary Correlative Studies ............................................................51 
6. 
TREATMENT PLAN ........................................................................................................55 
6.1 
Agent Administration .............................................................................................55 
6.2 
Definition of Dose-Limiting Toxicity ....................................................................59 
6.3 
General Concomitant Medication and Supportive Care Guidelines ......................61 
6.4 
Duration of Therapy ...............................................................................................62 
6.5 
Duration of Follow-Up ..........................................................................................62 
6.6 
Cross-over ..............................................................................................................63 
7. 
DOSING DELAYS/DOSE MODIFICATIONS................................................................63 
7.1 
Safety Management Guidelines .............................................................................67 

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7 
8. 
PHARMACEUTICAL INFORMATION ..........................................................................72 
8.1 
CTEP IND Agent ...................................................................................................72 
8.2 
Commercial Agent(s) .............................................................................................77 
9. 
STATISTICAL CONSIDERATIONS...............................................................................78 
9.1 
Study Design/Endpoints.........................................................................................78 
9.2 
Sample Size/Accrual Rate ......................................................................................81 
9.3 
Stratification Factors ..............................................................................................82 
9.4 
Analysis of Secondary Endpoints ..........................................................................82 
9.5 
Reporting and Exclusions ......................................................................................82 
9.6 
Data Safety Monitoring Board ...............................................................................83 
10. 
ADVERSE EVENTS:  LIST AND REPORTING REQUIREMENTS ............................83 
10.1 
Comprehensive Adverse Events and Potential Risks List(s) (CAEPRs) ...............83 
10.2 
Adverse Event Characteristics ...............................................................................87 
10.3 
Expedited Adverse Event Reporting ......................................................................88 
10.4 
Routine Adverse Event Reporting .........................................................................91 
10.5 
Pregnancy ...............................................................................................................91 
10.6 
Secondary Malignancy ...........................................................................................91 
10.7 
Second Malignancy ................................................................................................92 
11. 
STUDY CALENDAR .......................................................................................................93 
12. 
MEASUREMENT OF EFFECT........................................................................................95 
12.1 
Antitumor Effect – ISCL/USCLC/EORTC Response Criteria for Mycosis 
Fungoides and Sezary Syndrome ...........................................................................95 
12.2 
Definitions of Study Endpoints ..............................................................................99 
13. 
STUDY OVERSIGHT AND DATA REPORTING / REGULATORY 
REQUIREMENTS ...........................................................................................................100 
13.1 
Study Oversight ...................................................................................................100 
13.2 
Data Reporting .....................................................................................................100 
13.3 
Data Quality Portal ..............................................................................................103 
13.4 
CTEP Multicenter Guidelines ..............................................................................103 
13.5 
Collaborative Agreements Language ...................................................................103 
13.6 
Genomic Data Sharing Plan .................................................................................105 
13.7 
Incidental/Secondary Findings Disclosure Procedure .........................................105 
14. 
CALIFORNIA CANCER CONSORTIUM (CCC) POLICIES FOR 
MONITORING CONSORTIUM TRIALS .....................................................................106 
15. 
REFERENCES ................................................................................................................107 
APPENDIX A 
PERFORMANCE STATUS CRITERIA ................................................112 
APPENDIX B 
FORMULA TO ESTIMATE RENAL FUNCTION USING 
SERUM CREATININE ...................................................................................................113 

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8 
APPENDIX C:  PATIENT CLINICAL TRIAL WALLET CARD ............................................114 
APPENDIX D 
TISSUE BIOPSY VERIFICATION .....................................................115 
APPENDIX E:  MODIFIED SEVERITY-WEIGHTED ASSESSMENT TOOL 
(MSWAT) 
..................................................................................................................116 
APPENDIX F:  STANDARDIZED MEDICAL PHOTOGRAPHY...........................................118 
 
 
 
 

NCI Protocol #:  10384 
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9 
1. OBJECTIVES 
 
1.1 
Primary Objectives 
 
1.1.1 Phase 1 
1.1.1.1 To characterize the safety and toxicity profile and to determine a safe recommended 
phase 2 dose (RP2D) of Hu5F9-G4 (magrolimab) when given in combination with 
mogamulizumab 
 
1.1.2 Phase 2 
1.1.2.1 To compare the proportion of patients who achieve a partial or complete response 
lasting at least 6 months (ORR6) of the combination of Hu5F9-G4 (magrolimab) and 
mogamulizumab versus mogamulizumab alone 
 
1.2 
Secondary Objectives 
 
1.2.1 Phase 1 
1.2.2 To observe and record anti-tumor activity.  Although the clinical benefit of these drugs 
has not yet been established, the intent of offering this treatment is to provide a possible 
therapeutic benefit, and thus the patient will be carefully monitored for tumor response 
and symptom relief in addition to safety and tolerability. 
 
1.2.3 Phase 2 
1.2.3.1 To compare the efficacy of the combination of Hu5F9-G4 (magrolimab) and 
mogamulizumab versus mogamulizumab alone with respect to the following endpoints: 
• Overall Response Rate (ORR); Overall Response Rate lasting at least 4 months 
(ORR4); Overall Response Rate lasting at least 12 months (ORR12) 
• Duration of response (DOR) 
• Progression-free survival (PFS) 
• Time to next treatment (TTNT) 
 
1.3 
Exploratory Objectives 
 
1.3.1 Phase 1 and Phase 2 
1.3.1.1 To identify potential biomarkers that correlate with response to mogamulizumab and 
Hu5F9-G4 (magrolimab) including 
• Expression of CCR4 
• Somatic mutations and germline polymorphisms 
• Phenotyping of lymphoma and immune microenvironment  
• Functional assay of phagocytosis 
 
2. BACKGROUND 
 
2.1 
Study Diseases 
 

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2.1.1 Cutaneous T-cell Lymphomas (CTCL) 
 
CTCLs encompass a heterogeneous group of lymphomas that involve the skin but may also 
involve lymph nodes, blood, and visceral organs.  CTCL comprises approximately 25% of all T-
cell lymphomas.  Mycosis fungoides (MF) is the most common type of CTCL.  MF exhibits an 
epidermotropic clonal expansion of CD4+ T helper cells that induces pleomorphic skin lesions.  
MF may present gradually over many years as an indolent, chronic skin disease or present with 
more rapidly advancing skin disease, especially in those with worse prognostic factors such as 
folliculotropism or large cell transformation.  Sézary syndrome (SS) is a leukemic variant of 
CTCL in which subjects have generalized erythroderma and are at risk for lymph node and 
visceral disease.  There has been a continued increase in overall annual incidence in MF/SS 
(currently approximately 0.9 per 100,000 persons in the United States) (Horwitz et al., 2008).  
There is a 2:1 male to female prevalence and peak age of presentation is 55 to 60 years.  It is 
rarely seen in the pediatric age group. 
 
The clinical presentation of MF/SS can vary widely among patients.  The International Society 
for Cutaneous Lymphomas/European Organization for Research and Treatment of Cancer 
(ISCL/EORTC) classification system includes a characterization of both the surface area of 
involved skin as well as the quality of the skin lesions (patch, plaque, or tumor).  Additionally, 
staging incorporates the burden of disease present in the blood and lymph node compartments, as 
well as the presence of any visceral sites of disease. 
 
Prognosis of patients with advanced stage (stage IIB and higher) remains poor with a median 
overall survival of 63 months (Scarisbrick et al., 2015).  The most important prognostic factors 
include overall clinical stage, T-classification, and extracutaneous disease.  Other factors 
associated with poor prognosis include older age, large cell transformation, and folliculotropic 
disease (Scarisbrick et al., 2015). 
 
Systemic therapies are the mainstay of treatment for patients with more advanced stage disease.  
These therapies include retinoids, low-dose methotrexate, interferons (alpha and gamma), 
extracorporeal photopheresis, histone deacetylase (HDAC) inhibitors (vorinostat, romidepsin), 
brentuximab vedotin, cytotoxic chemotherapeutic agents (pralatrexate, liposomal doxorubicin, 
gemcitabine), pembrolizumab, and mogamulizumab.  Despite the large number of agents 
available for treatment, response rates to most treatments are 30-35% (Scarisbrick et al., 2015).  
Complete responses are uncommon, and the duration of response tends to be short-lived, 
typically 6-12 months.  There is a need for new therapies capable of yielding more durable 
responses. 
 
2.1.2 Chemokine Receptor 4 (CCR4) and T-cell lymphoma 
 
CCR4 is a chemokine receptor for both macrophage-derived chemokine (MDC, CCL22) and 
thymus- and activation-regulated chemokine (TARC, CCL17).  It is expressed by certain T-cell 
subsets including regulatory T-cells (Tregs), cutaneous lymphocyte antigen-positive skin-homing 
T cells and some Th2 cells.  CCR4 expression on Tregs appears to be selective for Forkhead Box 
P3 (FOXP3)hi, CD45RA- “effector-type” Tregs that are a potently suppressive class of Tregs 
(Sugiyama et al., 2013).  Therefore, therapies targeting CCR4 are currently being explored as a 

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form of cancer immunotherapy to deplete Tregs and promote tumor immunity (Sugiyama et al., 
2013; Berlato et al., 2017; Tanaka and Sakaguchi, 2017). 
 
CCR4 is also frequently expressed by the neoplastic T-cell in several T-cell malignancies.  
CCR4 expression was detectable in skin biopsies in 100% of 290 patients with MF or SS without 
large cell transformation (Kim et al., 2018) and was expressed on ≥10% of the infiltrating 
lymphoid cells in 97% (280/290) of patients.  Expression of CCR4 in patients with MF/SS with 
large cell transformation has ranged from 41-100% in small studies (Jones et al., 2000; Ishida et 
al., 2004).  CCR4 is also frequently expressed in ATLL, with expression detected in 88% 
(91/103) of patients (Ishida et al., 2004).  Other subtypes of peripheral T-Cell lymphoma (PTCL) 
including anaplastic large cell lymphoma (ALCL), PTCL-not otherwise specified (PTCL-NOS), 
angioimmunoblastic T-cell lymphoma (AITL), and natural killer (NK)/T-cell lymphomas may 
express CCR4.  One study found expression of CCR4 in 28% of PTCL cases when excluding 
ATLL and CTCL (Ishida et al., 2004).  Another phase 2 trial that enrolled CCR4- expressing 
PTCL and CTCL found 78% of screened patients had CCR4 expression (defined as ≥10% 
expression by tumor cells) (Ogura et al., 2014). 
 
2.2 
CTEP IND Agent 
 
2.2.1 Hu5F9-G4 (magrolimab) 
 
Hu5F9-G4 (magrolimab) is a first-in-class anticancer therapeutic agent targeting the cluster of 
differentiation (CD) 47 signal regulatory protein alpha (SIRPα) axis (Liu, J., et al., 2015; Huang 
et al., 2017).  Hu5F9-G4 (magrolimab) is a recombinant humanized anti-CD47 monoclonal 
antibody of the IgG4 kappa isotype containing a Ser-Pro (S-P) substitution in the hinge region 
(position 228) of the heavy chain to reduce fragment antigen-binding (Fab) arm exchange (Liu, 
J.,  et al., 2015).  Hu5F9-G4 (magrolimab) binds to human CD47 on target malignant cells, 
blocks the anti-phagocytic signal to macrophages, enhances tumor cell phagocytosis, and elicits 
an anti-tumor T-cell response (Huang et al., 2017; Liu et al., 2017). 
 
Hu5F9-G4 (magrolimab) blocks the interaction of CD47 with its ligands and enables 
phagocytosis of human cancer cells (Liu, J., et al., 2015).  The activity of Hu5F9-G4 
(magrolimab) is primarily dependent on blocking CD47 binding to SIRPα and not on the 
recruitment of fragment crystallizable (Fc)-dependent effector functions.  Most normal cells lack 
expression of pro-phagocytic signals and are unaffected by Hu5F9-G4 (magrolimab) binding to 
CD47 (Feng et al., 2015).  However, blockade of CD47 in tumors can enhance macrophage 
phagocytosis of cancer cells, and in preclinical studies, this results in a profound antitumor effect 
against solid tumors and hematological malignancies (Liu, J., et al., 2015; Chan et al., 2009).   
 
CD47 is widely expressed and has been identified as a key molecule mediating cancer cell 
evasion of phagocytosis by the innate immune system (Liu, J., et al., 2015).  It provides an anti-
phagocytic signal by binding to the N-terminus of SIRPα on immune cells and suppresses 
phagocytosis (Huang et al., 2017).  Hematopoietic stem cells transiently upregulate CD47 
expression to escape phagocytosis by macrophages before and during mobilization (Jaiswal et 
al., 2009).  The pathological role of CD47 is commonly responsible for the escape of malignant 
cancer cells from immune- surveillance.  CD47 expression is increased on the surface of cancer 

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cells from many diverse human tumor types including head and neck cancer, melanoma, breast, 
lung, ovarian, pancreatic, colon, bladder, prostate, leiomyosarcoma, glioblastoma, 
medulloblastoma, glioma, lymphoma, leukemia, and multiple myeloma (Chan et al., 2009; 
Jaiswal et al., 2009; Majeti et al., 2009; Chao et al., 2010a; Chao et al., 2010b; Chao et al., 2012; 
Krampitz et al., 2016; Edris et al., 2012; Gholamin et al., 2017, Weiskopsf et al., 2016).  CD47 
overexpression has been associated with poor prognosis in leukemia, non-Hodgkin lymphoma 
(NHL), bladder cancer, breast cancer, and other cancers (Huang et al., 2017; Majeti et al., 2009; 
Chao et al., 2010a; Chan et al., 2009; Willingham et al., 2012).  Furthermore, elevated CD47 
messenger RNA (mRNA) expression correlates with a worse overall survival for multiple types 
of cancer (Willingham et al., 2012).  In murine xenograft studies, CD47-blocking antibodies can 
inhibit human cancer growth and metastasis by enabling the phagocytosis of cancer stem cells 
(CSCs) from various hematological malignancies and solid tumors.  CD47-blocking antibodies 
have been shown to exhibit potent synergy with tumor-specific monoclonal antibodies, such as 
rituximab, cetuximab, and trastuzumab (Chao et al., 2010a; Weiskopf et al., 2013).   
 
Hu5F9-G4 (magrolimab) has demonstrated antitumor activity in breast, ovarian, brain, and 
bladder cancers, acute myeloid leukemia (AML), NHL, and other malignancies in preclinical 
studies (Chan et al., 2009, Gholamin et al., 2017, Liu, J., et al., 2015, Sikic et al., 2019, 
Willingham et al., 2012).   
 
2.2.1.1 Mechanism of Action 
 
Hu5F9-G4 (magrolimab) is an anti-CD47 monoclonal antibody that disrupts the CD47/SIRPα 
interaction to induce macrophage-mediated phagocytosis (Liu, J., et al., 2015).  Hu5F9-G4 
(magrolimab) selectively binds to CD47 on tumor cells and prevents it from binding to SIRPα.  
This inhibits CD47/SIRP signaling, causing the activation of macrophages which in the presence 
of additional prophagocytic signals, such as calreticulin can initiate specific tumor cell 
phagocytosis (Chao et al., 2010b).  Inhibiting CD47 signaling can also initiate an anti-tumor T-
lymphocyte immune response and T-cell-mediated killing (Liu, X., et al., 2015). 
 
2.2.1.2 
Summary of Nonclinical Experience 
 
The therapeutic effect of Hu5F9-G4 (magrolimab) was evaluated in human AML xenograft 
models in vivo with two independent primary patient samples (SU028 and SU048) 
(Investigator’s Brochure, 2019).  Therapy was initiated with daily intraperitoneal (IP) injection 
of either control mouse IgG or 100 mcg of Hu5F9-G4 (magrolimab).  The therapeutic response 
was monitored by analyzing the burden of AML cells in repeated bone marrow aspirates.  Daily 
doses of 100 mcg of Hu5F9-G4 (magrolimab) over 2 weeks cleared AML in the bone marrow of 
all mice at the end of treatment with recovery of normal hematopoiesis in the bone marrow, 
leading to a major survival benefit compared to control.    
 
The pharmacokinetics (PK) and toxicokinetics (TK) of Hu5F9-G4 (magrolimab) were studied in 
single- and repeat-dose (non-Good Laboratory Practice [GLP] and GLP) studies in the 
cynomolgus monkey and an 8-week pivotal toxicology study (Investigator’s Brochure, 2019).  
Hu5F9-G4 (magrolimab) has nonlinear PK with a varied half-life (t1/2), ranging from 
approximately 5 to 250 hours following single and multiple doses.  The volume of distribution 

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approximated monkey serum volume, as expected for a monoclonal antibody.  The t1/2 appears to 
increase and clearance appears to decrease with increasing dose and with repeated dosing, 
suggesting saturation of target-mediated clearance (CL) through the endogenous CD47 cellular 
sink.  
 
2.2.1.2 Summary of Clinical Experience 
 
As of July 24, 2019, 401 patients have received Hu5F9-G4 (magrolimab) as monotherapy and in 
combination in six company sponsored clinical trials (SCI-CD47-001, SCI-CD47-002, 5F9003, 
5F9004, 5F9005, and 5F9006) (Investigator’s Brochure, 2019).  The two monotherapy studies 
include Study SCI-CD47-001, a phase 1 study in advanced solid tumor and lymphoma patients 
and Study SCI-CD47-002, a phase 1 study in relapsed/refractory (R/R) AML patients.  The four 
combination studies include Study 5F9003, a phase 1b/2 of Hu5F9-G4 (magrolimab) with 
rituximab in NHL patients; Study 5F9004, a phase 1b/2 of Hu5F9-G4 (magrolimab) with 
cetuximab in solid tumor and colorectal cancer (CRC) patients; Study 5F9005, a phase 1b study 
of Hu5F9-G4 (magrolimab) with azacitidine in AML and myelodysplastic syndrome (MDS) 
patients; and Study 5F9006, a phase 1b study of Hu5F9-G4 (magrolimab) with avelumab in solid 
tumor and ovarian cancer patients. 
 
2.2.1.2.1 
Clinical Pharmacokinetics (PK) 
 
The PK data are available from 58 patients in the first in human (FIH) study, Study SCI-CD47-
001 (Investigator’s Brochure, 2019).  Hu5F9-G4 (magrolimab) was administered at a dose range 
of .01 mg/kg to 30 mg/kg.  The area under the concentration-time curve (AUC) and maximum 
plasma concentration (Cmax) show greater than dose-proportional increases at doses ≤10 mg/kg 
and dose-proportional changes at 10 to 30 mg/kg.  After priming dose of 1 mg/kg, a geometric 
mean Cmax of 0.682 mcg/mL (mg/L) was observed.  After the second dose of 1 mg/kg, the 
geometric mean Cmax was approximately 10-fold higher at 5.83 mcg/mL.  On continuous dosing, 
the geometric mean Cmax increased by another 2-fold to approximately 10 mcg/mL.  The increase 
after the second dose was consistent with multiple dose accumulation.  This suggests time-
dependent PK at 1 mg/kg between the first and the second doses.  Due to the small number of 
patients, this phenomenon could not be characterized at other doses.  The mean terminal t1/2 
derived from the PK parameters was approximately 2 weeks at doses ≥10 mg/kg weekly.  The 
PK of Hu5F9-G4 (magrolimab) is similar to other humanized monoclonal antibodies targeted 
towards cell-surface receptors.  After multiple weekly doses ≥10 mg/kg, the CD47 antigen sink 
is fully saturated. 
 
The rate of anti-drug antibody (ADA) occurrence was low (<10%) and typical for a humanized 
antibody (Investigator’s Brochure, 2019).  Comparison of the PK of the ADA-positive and 
ADA-negative patients indicated that there was no impact of ADA occurrence on PK.  There was 
no clear correlation between ADA occurrence and safety events. 
 
2.2.1.2.2 
Clinical Safety Summary 
 
As of July 24, 2019, 401 (324 solid tumor/lymphoma and 77 AML/MDS patients) patients have 
received at least one dose of Hu5F9-G4 (magrolimab) as monotherapy or in combination 

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(Investigator’s Brochure, 2019).  Patients reported anemia (35.9%), fatigue (31.9%), headache 
(30.7%), infusion-related reaction (IRR) (25.7%), pyrexia (22.9%), chills (21.4%), nausea 
(19.5%), hemagglutination (14.5%), and vomiting (11.0%) as the most common treatment-
related adverse events (AEs).  
 
A total of 397 serious adverse events (SAEs) have been reported in patients across all six clinical 
studies (Investigator’s Brochure, 2019).  The most commonly reported SAEs include febrile 
neutropenia (40 events), IRRs (23 events), malignant neoplasm progression (20 events), small 
intestinal obstruction (17 events), pneumonia (16 events), anemia (15 events), and pyrexia (14 
events).  Only three of the febrile neutropenia SAEs were considered related to Hu5F9-G4 
(magrolimab) and none were reported in Studies 5F9004 and 5F9006, which enrolled only solid 
tumor patients.  Twenty-one IRRs were considered related to Hu5F9-G4 (magrolimab), one was 
attributed to cetuximab only, and one was attributed to rituximab only. 
 
Of the 397 SAEs, 86 were considered related to Hu5F9-G4 (magrolimab) (Investigator’s 
Brochure, 2019).  The most frequently reported serious adverse reactions (SARs) included IRR 
(21 events), anemia (11 events), pyrexia (7 events), and thrombocytopenia (4 events).  Anemia 
and IRR have been identified as risks associated with Hu5F9-G4 (magrolimab), and four of the 
seven pyrexia SARs occurred within the 24 hours following a Hu5F9-G4 (magrolimab) infusion 
and could, therefore, be considered part of an IRR.  No maximum tolerated dose (MTD) has 
been determined as monotherapy or in combination.  No deaths have been attributed to Hu5F9-
G4 (magrolimab) administration. 
 
The RP2D for solid tumor and lymphoma patients is 1 mg/kg (priming) followed by 30 mg/kg 
once every week for the first two cycles (28 days/cycle), followed by a dose of 30 mg/kg every 2 
weeks (Investigator’s Brochure, 2019).  In MDS and AML patients, the RP2D is 1 mg/kg 
priming on Days 1 and 4 followed by 15 mg/kg on day 8 and 11 and then 30 mg/kg on days 15, 
and 22.  Weekly doses are continued in Cycle 2 and then in Cycle 3 and beyond 30 mg/kg every 
2 weeks is administered.  All cycles are 28 days long. 
 
If patients have completed at least 1 cycle of dosing but have a treatment delay of greater than 4 
weeks, then re-priming with the Cycle 1 doses and schedules should be instituted upon starting 
retreatment.  Treatment interruptions of less than 4 weeks can resume the treatment schedule 
without re-priming. 
 
2.2.1.2.3 
Clinical Efficacy Summary 
 
In the FIH study, Study SCI-CD47-001, 62 solid tumor and lymphoma patients received Hu5F9-
G4 (magrolimab) as monotherapy and were evaluable for efficacy (Investigator’s Brochure, 
2019).  Two of these patients had refractory diffuse large B-cell lymphoma (DLBCL) (Sikic et 
al., 2019).  An additional 10 patients were treated in the CTCL cohort.  In the dose-escalation 
cohorts, 13 treated patients had a diagnosis of ovarian or fallopian tube cancers.  Two of these 
patients, both heavily pretreated and who received 20 mg/kg Hu5F9-G4 (magrolimab), had 
confirmed partial responses (PRs) with 50% and 44% reduction in tumor measurements.  These 
patients were on treatment for 5.2 and 9.2 months before progressing and they had received more 
than six prior lines of systemic therapy.  No objective responses were observed in other patients.  

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In the dose escalation cohort, two patients with refractory DLBCL were treated with Hu5F9-G4 
(magrolimab) monotherapy.  No objective responses were observed; however, one patient had a 
mixed response (significant decrease in size of multiple tumor lesions, with increase size in 
others). 
 
For the CTCL patients, 10 patients were treated with Hu5F9-G4 (magrolimab) monotherapy at 
doses of 20 or 30 mg/kg in Study SCI-CD47-001, and response data are available for 8 CTCL 
patients (Investigator’s Brochure, 2019).  No objective responses were observed; however, six 
patients had stable disease (SD), and two patients had disease progression (PD) as their best 
response. 
 
As of May 2019, Studies SCI-CD47-002 and 5F9005 evaluated efficacy in AML and MDS 
patients who received Hu5F9-G4 (magrolimab) as monotherapy and in combination with 
azacytidine (Investigator’s Brochure, 2019).  Twenty patients (all AML) were treated in Study 
SCI-CD47-002 study, and 57 patients (10 R/R AML and MDS, 46 treatment-naïve and unfit for 
standard induction therapy [TN/U] AML, and 1 rollover cohort) were treated in the Study 
5F9005.  In Study SCI-CD47-002, 58% of evaluable patients had a reduction in bone marrow 
blasts, but no objective responses were observed.  Two of 18 evaluable patients with long-term 
SD had marked reductions in bone marrow cellularity, with 1 remaining on treatment for greater 
than 11 months.  One of these patients had a decrease in bone marrow blast count >50% and had 
a significant increase in T-cell infiltrate in the bone marrow; this patient was on therapy for 11.8 
months.  In the monotherapy portion of Study 5F9005, the ORR was 10% with one AML patient 
achieving a response of morphologic leukemia-free state.  In the combination portion of Study 
5F9005, 25 patients were evaluable for efficacy.  In AML, 64% of patients achieved an objective 
response, including 55% with complete response (CR) + PR.  Bone marrow blast reduction was 
observed in all but one patient on the Hu5F9-G4 (magrolimab) plus azacitidine combination.  
Hu5F9-G4 (magrolimab) in combination with azacytidine induced high ORRs in newly 
diagnosed AML patients who are ineligible for induction chemotherapy and newly diagnosed 
MDS patients who are intermediate to very high risk by Revised International Prognostic 
Scoring System (IPSS-R). 
 
In Study 5F9003, NHL patients received Hu5F9-G4 (magrolimab) in combination with 
rituximab (Investigator’s Brochure, 2019).  Efficacy was evaluated in a total of 97 patients, 
including 59 DLBCL patients, 35 follicular lymphoma (FL) patients, and 3 marginal zone 
lymphoma (MZL) patients.  The overall ORR for all patients who received at least one dose of 
Hu5F9-G4 (magrolimab) and had at least one post treatment response assessment was 45%, with 
19% achieving a best response of CR.  In patients with DLBCL, the ORR was 36%, with 15% 
achieving a CR.  In FL and MZL, the ORR was 61%, with 24% achieving CR.  Median time to 
response (TTR) was 1.7 months (range 1.6 to 6.6 months).  In Phase 1b of the study, the median 
DOR was not reached for either DLBCL or FL patients with a median follow-up of 13.8 and 21 
months, respectively. 
 
2.3 
Other Agent 
 
2.3.1 Mogamulizumab (KW-0761) 
 

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Mogamulizumab is a defucosylated, humanized, monoclonal antibody with enhanced antibody 
dependent cellular cytotoxicity (ADATA COORDINATING CENTER) targeting CCR4.  The 
lack of fucose results in the antibody eliciting more potent ADATA COORDINATING 
CENTER than conventionally produced antibodies.  Mogamulizumab does not induce 
complement dependent cytotoxicity.  In 2018, the FDA approved mogamulizumab for the 
treatment of patients with relapsed or refractory MF/SS after at least one prior systemic therapy.  
This approval was based on the pivotal phase 3 MAVORIC trial.  This randomized, open-label 
trial enrolled 370 patients who were randomized to either mogamulizumab or vorinostat (Kim et 
al., 2018).  The trial demonstrated a significant improvement in the primary endpoint of PFS 
with mogamulizumab treatment as compared to vorinostat (median 7.7 months versus 3.1 
months).  Improvements were also seen in secondary endpoints including ORR (28% versus 5%) 
and DOR (median 14.1 months versus 9.1 months).  Responses to mogamulizumab were most 
notable in the blood compartment with a response rate of 68% in blood compartment vs 42% in 
the skin compartment and only 17% in the nodal compartment.  Importantly, patients with large-
cell transformation (LCT) were excluded from this trial, despite evidence that CCR4 is expressed 
in MF with LCT (Jones et al., 2000). 
 
In addition to CTCL and ATLL, mogamulizumab has demonstrated some efficacy in other 
subtypes of PTCL.  A Japanese multicenter phase 2 study that included relapsed and refractory 
CCR4-expressing PTCL found an ORR of 34% in PTCL histologies including PTCL-NOS, 
AITL, and ALK-negative ALCL (Ogura et al., 2014).  A similar European phase 2 study showed 
an ORR of 13% in PTCL histologies.  In trials of both CTCL and PTCL, there has not been an 
association found between the level of expression of CCR4 and responses to mogamulizumab 
(Kim et al., 2018; Ogura et al., 2014).  The CCR4 gene is mutated in 29% of ATLL, resulting in 
a gain of function and increased expression (Kataoka et al., 2015).  Patients with a gain-of-
function mutation in CCR4 appear to greatly benefit from mogamulizumab treatment with a 5-
year overall survival of 73% versus 26% in patients without CCR4 mutations (Sakamoto et al., 
2018) 
 
Mogamulizumab is generally well-tolerated.  The most common ≥ grade 3 AEs in the 184 
patients treated in the MAVORIC trial were rash/drug eruptions, which led to discontinuation in 
7% of mogamulizumab-treated patients. 
 
2.4 
Rationale 
 
2.4.1 CD47 as a Therapeutic Target for T-cell lymphomas 
 
CD47 is a surface protein expressed by many normal cells but is frequently overexpressed by 
cancer cells (Chao et al., 2011; Chao et al., 2010b; Jaiswal et al., 2009; Majeti et al., 2009).  One 
of the primary ligands for CD47 is SIRPα, which is expressed on the surface of macrophages, 
among other cell types (Adams et al., 1998).  Engagement of CD47 by SIRPα produces an 
inhibitory signal that decreases the phagocytic function of the macrophage (Weiskopf and 
Weissman , 2015).  It is now recognized that anti-phagocytic signaling through the CD47/SIRPα 
axis is an important mechanism of cancer evasion from phagocytic clearance.  Blockade of 
CD47/SIRPα signaling, for example by antibodies targeting CD47, can promote phagocytosis 
and elimination of tumor cells (Chao et al., 2010a).  Murine patient xenograft models have 

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demonstrated that antibodies blocking CD47 promote phagocytosis of lymphoma cells and 
inhibit human lymphoma growth (Chao et al., 2010a).  Sezary cells have high expression of 
surface CD47 and overexpression associates with a worse prognosis (Johnson et al., 2019).  
When co-incubated with macrophages, blockade of CD47 promoted selective phagocytosis of 
Sezary cells, but not normal CD4 T-cells (Johnson et al., 2019). 
 
TTI-621 is a decoy receptor for CD47 capable of blocking CD47/SIRPα signaling.  The 
molecule is an ADATA COORDINATING CENTER-competent fusion protein composed of the 
CD47-binding domain of human SIRPα linked to the Fc region of human immunoglobulin G1.  
A multicenter phase 1 study of TTI-621 in relapsed and refractory MF/SS has yielded promising 
results (Querfeld et al., 2018).  This trial treated patients with intralesional injection of TTI-621.  
Rapid responses were observed even after a single dose.  Remarkably, these responses were not 
limited to the injected lesion, as abscopal responses were common.  In all, 15 of 17 patients 
(88%) had some measurable improvement and 7 of 17 patients (41%) had ≥50% improvement in 
measured lesions.  Thus, it appears blockade of CD47 signaling may be an effective strategy for 
CTCL. 
 
2.4.2 Rationale for the combination of mogamulizumab and Hu5F9-G4 (magrolimab) 
 
There is strong preclinical and clinical rationale to support the combination of Hu5F9-G4 
(magrolimab) with tumor-targeting monoclonal antibodies.  While cancers appear to be more 
susceptible to CD47 blockade than normal cells, the efficacy of anti-CD47 antibodies can be 
augmented by combining with tumor-specific antibodies.  Mouse xenograft models demonstrated 
a strong synergy between anti- CD47 and rituximab (Figure 4) (Chao et al., 2010a).  The 
synergistic activity of CD47 blockade with tumor-targeting antibodies has now been validated by 
a phase 1b study combining Hu5F9-G4 (magrolimab) with rituximab in relapsed or refractory B-
cell lymphomas (Figure 4) (Advani et al., 2018).  In this 22-patient trial (15 patients with diffuse 
large B-cell lymphoma and 7 patients with follicular lymphoma), the ORR was 50% with 36% of 
patients having a CR.  Notably, 95% of patients had disease that had been refractory to 
rituximab.  Thus, Hu5F9-G4 (magrolimab) appears to synergize safely and effectively with 
tumor-specific monoclonal antibodies.  Given the excellent safety data of mogamulizumab, it is 
very likely that the combination of mogamulizumab and Hu5F9-G4 (magrolimab) will be safe 
and well-tolerated. 
 

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Figure 4: (A) NOD scid gamma (NSG) mice transplanted with Raji cells were treated with the 
indicated antibodies.  Tumor volume is shown on top and Kaplan-Meier survival plots on bottom 
(Chao et al., 2010a).  (B) positron emission tomography (PET) scan before and after Hu5F9-G4 
(magrolimab) and Rituximab treatment in a patient with DLBCL (Advani et al., 2018) 
 
2.4.3 Rationale For Use of Priming Dose for Hu5F9-G4 (magrolimab) 
 
Because of the IgG4 isotype, Hu5F9-G4 (magrolimab) does not induce effective Fc-dependent 
effector functions.  This results in reduced phagocytosis of normal cells, which lack expression 
of natural pro-phagocytic signals (Feng et al., 2015).  The exception to this is erythrocytes, 
which do acquire natural pro-phagocytic signals as they age.  Blockade of CD47 with Hu5F9-G4 
(magrolimab) causes a dose-dependent anemia due to the rapid clearance of aged erythrocytes 
(Sikic et al., 2019).  Subsequently, a dose priming strategy has been adopted to mitigate this 
toxicity.  This entails a single, subtherapeutic priming dose of Hu5F9-G4 (magrolimab) to induce 
clearance of older erythrocytes.  This allows sufficient time to induce a compensatory 
reticulocytosis before the first full dose of Hu5F9-G4 (magrolimab) is given.  This strategy 
appears to limit the degree and duration of anemia associated with Hu5F9-G4 (magrolimab) 
treatment (Figure 5). 
 

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Figure 5: Anemia and reticulocyte kinetics with Hu5F9-G4 (magrolimab) priming strategy 
(Sikic et al, 2019) 
 
2.4.4 Rationale for the proposed trial dosing schema 
 
Analogous to the combination with rituximab, we hypothesize that Hu5F9-G4 (magrolimab) will 
have synergistic efficacy when combined with mogamulizumab in CCR4-expressing T-cell 
lymphomas.  We also propose that the combination may be effective even in patients with prior 
mogamulizumab exposure based on the experience with rituximab and Hu5F9-G4 (magrolimab).  
The dosing schema proposed here follows the FDA-approved dosing for mogamulizumab.  No 
dose-limiting toxicities (DLTs) were identified in the phase 1/2 study of mogamulizumab and the 
dose regimen was selected based on the PK profile of mogamulizumab.  Because the mechanism 
of action of Hu5F9-G4 (magrolimab) synergy relies on a constant presence of pro-phagocytic 
signaling from the mogamulizumab Fc receptor, optimal efficacy will require continuous dosing.  
The phase 1b portion of this trial will aim to determine a safe dose of Hu5F9-G4 (magrolimab).  
We will target a dose of 30 mg/kg given every 2 weeks, which was been shown to be sufficient 
to achieve near 100% CD47 receptor occupancy (Figure 6).  Because of the excellent safety 
profile of each individual drug, and the lack of synergistic toxicity seen in the combination trial 
with rituximab, we expect this combination to be safe and well-tolerated.  Accordingly, we have 
selected a dose de-escalation design that will start at the target Hu5F9-G4 (magrolimab) dose of 
30 mg/kg.  If there is unacceptable toxicity at this dose, we will reduce the Hu5F9-G4 
(magrolimab) dose to 20 mg/kg, which was shown to maintain excellent tumor penetrance into 
lymph nodes (Figure 6). 
 
As of the July 2023 amendment, the phase 1b portion has been completed with an enrollment of 
6 patients at dose level 1.  Out of the 6 patients treated, 1 experienced a DLT.  The recommended 
phase 2 dose (RP2D) has been established as dose level 1 (30mg/kg magrolimab starting cycle 
1). 
 

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Figure 6: Top shows CD47 receptor occupancy on erythrocytes and leukocytes at a dose of 30 
mg/kg every 2 weeks.  Bottom shows detection of Hu5F9-G4 (magrolimab) in a malignant 
lymph node in a patient treated at a dose of 20 mg/kg. (Sikic et al., 2019) 
 
2.4.5 Rationale for the primary endpoint in the primary phase 2 cohort 
 
CTCL has unique symptoms, including disturbing visible and pruritic qualities that impact 
treatment decisions, complicating traditional trial endpoints, including ORR, PFS, and DOR.  
Objective responses with >50% reduction may not equal clinical benefit, and symptomatic 
patients often elect to transition to new therapy without objective progression, censoring them 
from PFS and DOR analysis.  Meaningful impact of CTCL therapy should reflect both ORR and 
DOR without the initiation of new treatment.  Therefore, composite endpoints that reflect both 
ORR and DOR are increasingly being explored in trials of CTCL (Kim et al., 2016).  In this trial, 
we have selected the primary endpoint of ORR6, defined as the rate of objective responses 
lasting at least 6 months without the initiation of new therapy.  Importantly, this new type of 
composite endpoint has been well-received by the FDA as a relevant endpoint for trials in CTCL.  
ORR4 (the rate of objective responses lasting at least 4 months without the initiation of new 
therapy) was the primary endpoint of the pivotal ALCANZA trial which lead to the FDA 
approval of brentuximab vedotin for the treatment of CD30-positive cutaneous T- cell 
lymphomas (Prince et al., 2017).  We believe that for this patient population, which differs from 
that of the ALCANZA trial, a response duration of 6 months would be more clinically 
meaningful and important than the shorter ORR4 endpoint. 
 
2.5 
Correlative Studies Background 
 
2.5.1 Integrated Correlative Study 
 

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2.5.1.1 CCR4 expression 
 
2.5.1.1.1 
Biologic rationale 
 
Mogamulizumab is an anti-CCR4 antibody.  The mechanism of action is believed to be through 
antibody dependent cell-mediated cytotoxicity and antibody dependent cellular phagocytosis.  
Thus, the efficacy of mogamulizumab with or without Hu5F9-G4 (magrolimab) will be 
dependent on CCR4 expression on the malignant T-cells.  While the vast majority of MF and SS 
express CCR4, it is unknown whether loss of the CCR4 antigen may emerge as a resistance 
mechanism to mogamulizumab. 
 
2.5.1.1.2 
Hypothesis  
 
Lymphomas with low or absent CCR4 expression will not respond to treatment with 
mogamulizumab or mogamulizumab plus Hu5F9-G4 (magrolimab). 
 
2.5.1.1.3 
Relevant preclinical and clinical data   
 
Preclinical data relevant to this assay is discussed in Section 2.1.2. 
 
2.5.2 Exploratory Correlative Studies 
 
2.5.2.1 Spatial association of tumor cells and components of the tumor microenvironment 
including macrophage enumeration and phenotyping 
 
2.5.2.1.1 
Biologic rationale  
 
The primary mechanism of action for Hu5F9-G4 (magrolimab) is believed to be through the 
promotion of phagocytosis by tumor-associated macrophages (TAMs).  The infiltration of TAMs 
in the tumor microenvironment, their polarization phenotype, and their spatial proximity to 
CTCL cells in the skin are all potential biomarkers to both predict response to anti-CD47 
therapy.   
 
2.5.2.1.2 
Hypothesis  
 
A spatial signature of macrophages in the skin tumor microenvironment will be identified that 
will correlate with response to therapy with mogamulizumab plus Hu5F9-G4 (magrolimab). 
 
2.5.2.1.3 
Relevant preclinical and clinical data   
 
Macrophages are a prominent component of the tumor microenvironment of CTCLs (Sugaya et 
al., 2012; Assaf and Hwang 2016; Wu et al., 2014).  In particular, M2 macrophages have been 
reported to appear to be play an important role in CTCL progression (Sugaya et al., 2012; Wu et 
al., 2014; Furudate et al., 2016).  Treatment with anti-CD47 antibodies have been shown to 
promote M1 macrophage polarization in murine glioblastoma models (Zhang et al., 2016). 
 

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2.5.2.2 Whole Exome Sequencing 
 
2.5.2.2.1 
Biologic rationale 
 
Somatic mutations involving CCR4, the target of mogamulizumab, have been described in 
MF/SS.  These mutations may affect the efficacy of the study drugs.  Germline polymorphisms 
in CD47 signaling pathway members may also affect the efficacy of Hu5F9-G4 (magrolimab).   
 
2.5.2.2.2 
Hypothesis  
 
C-terminal “gain-of-function” mutations of CCR4 will confer an improved ORR6.  One or more 
polymorphisms in the CD47 pathway may be associated with improved ORR6. 
 
2.5.2.2.3 
Relevant preclinical and clinical data 
 
CCR4 gain of function mutations are known to confer an improved outcome in ATLL (Sakamoto 
et al., 2018).  Subsequently, CCR4 mutations have been discovered CTCL (Wang et al., 2015).  
However, it is unknown whether these mutations will confer a similar improved outcome in 
response to mogamulizumab treatment in CTCL.  Preclinical data has suggested that 
polymorphisms in SIRP may confer improved outcomes in response to CD47 therapy (Wong et 
al., 2014).  Similarly, polymorphisms in the Fc receptor genes may promote antibody-dependent 
clinical responses (Zhang et al., 2007).    
 
2.5.2.3 RNA Sequencing 
 
2.5.2.3.1 
Biologic rationale  
 
Transcriptional profiles of CTCL have been shown to be prognostic.  These transcriptomes may 
also yield a signature that could be predictive of response or resistance to CCR4/CD47 targeted 
therapy.  Additionally, paired transcriptomes before treatment and at progression may elucidate 
novel molecular mechanisms of resistance. 
 
2.5.2.3.2 
Hypothesis 
 
Transcriptome profiling of samples will reveal a gene signature that correlates with response to 
treatment with mogamulizumab plus Hu5F9-G4 (magrolimab).   
 
2.5.2.3.3 
Relevant preclinical and clinical data  
 
Multiple studies have found prognostic gene expression signatures in CTCL patients (Litvinov et 
al., 2015; Litvinov et al., 2017 ).  CCR4 gene expression has been shown to not only distinguish 
CTCL from benign skin biopsies, but also is prognostic (Litvinov et al., 2017). 
 
2.5.2.4 Phagocytosis Index 
 

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2.5.2.4.1 
Biologic rationale  
 
T-cell lymphomas display marked variability in their susceptibility to phagocytosis in the 
presence or absence of CD47-blocking antibodies.  An in vitro phagocytosis assay, with or 
without CD47-blocking antibodies may identify lymphomas with the highest phagocytic 
potential. 
 
2.5.2.4.2 
Hypothesis  
Patients with the greatest phagocytic response to CD47 blockade in an in vitro assay may derive 
the greatest benefit from CD47-targeting therapy. 
 
2.5.2.4.3 
Relevant preclinical and clinical (if available) data   
 
It has been shown that T-cell lymphomas are not effectively targeted by CD47-blocking 
antibodies that lack a functional Fc, but that addition of a tumor-targeting antibody such as 
mogamulizumab can synergize with CD47 blockage (Jain et al., 2019).  Primary T-cell 
lymphomas intrinsically vary greatly in their susceptibility to CD47 blockade in vitro, but it is 
unknown whether performance in an in vitro assay of phagocytosis will correlate with clinical 
activity. 
 
2.5.2.5 Immunophenotyping of circulating tumor cells 
 
2.5.2.5.1 
Biologic rationale  
 
Levels of expression of CCR4 and CD47 may correlate with responses to therapy with 
mogamulizumab plus Hu5F9-G4 (magrolimab).  Because a significant proportion of patients are 
anticipated to have circulating leukemic disease, we can phenotype circulating tumor cells to 
measure the expression of these markers, and to also estimate the fraction of other potentially 
relevant immune populations in the blood such as monocytes.   
 
2.5.2.5.2 
Hypothesis  
 
Low CCR4 and/or CD47 expression on circulating Sezary cells will be correlated with worse 
clinical outcomes.  
 
2.5.2.5.3 
Relevant preclinical and clinical data   
 
While the expression of CCR4 can vary greatly on circulating Sezary cells (Duvic et al., 2015), it 
is unclear whether higher levels of expression may correlate with improved clinical responses.  
Additionally, mogamulizumab has been shown to reduce the number of circulating regulatory T-
cells (Ni et al., 2015).  It is possible that the combination of mogamulizumab plus Hu5F9-G4 
(magrolimab) may be more potent in clearing regulatory T-cells.   
 
2.5.2.6 T cell receptor sequencing 
 

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2.5.2.6.1 
Biologic rationale  
 
High throughput sequencing of the T-cell receptor is a more sensitive and specific method to 
track minimal residual disease (MRD) in patients with T-cell lymphoma.   
 
2.5.2.6.2 
Hypothesis  
 
Patient with the greatest reduction in MRD or with undetectable MRD after treatment will have a 
higher ORR6 and greater duration of response. 
 
2.5.2.6.3 
Relevant preclinical and clinical data   
 
TCR sequencing has emerged as a powerful tool to sensitively and specifically track CTCL cells 
in skin and blood (Kirsch et al., 2015).  Minimal residual disease monitoring by TCR sequencing 
has correlated with outcomes in the setting of allogeneic stem cell transplantation (Weng et al., 
2013).   
 
3. PATIENT SELECTION 
 
3.1 
Eligibility Criteria  
 
3.1.1 Diagnosis of either MF or SS by the World Health Organization (WHO) 2016 
classification (Swerdlow et al., 2017), stage IB-IV by modified International Society for 
Cutaneous Lymphomas (ISCL)/ European Organization of Research and Treatment of 
Cancer (EORTC) classification (Olsen et al., 2011), without large cell transformation 
(LCT) at the time of screening.  Patients with a history of prior LCT are permitted. 
 
3.1.2 Patients must have had at least one prior course of systemic therapy. 
 
3.1.3 Age ≥18 years.   
 
Because no dosing or adverse event data are currently available on the use of Hu5F9-G4 
(magrolimab) in combination with mogamulizumab in patients <18 years of age, children 
are excluded from this study, but will be eligible for future pediatric trials.   
 
3.1.4 ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A). 
 
3.1.5 Patients must have adequate organ and marrow function as defined below: 
 
− 
Hemoglobin 
 
≥9.5 g/dL and transfusion independence (defined as  
not requiring more than 2 units of red blood cell  
(RBC) transfusions during the 4-week period prior  
to screening) 
− 
absolute neutrophil count 
 
≥1,000/mcL 
− 
platelets  
 
≥75,000/mcL  
− 
total bilirubin 
 
≤1.5 × institutional upper limit of normal (ULN)  

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except for subjects with Gilbert’s syndrome or  
genetic equivalent 
− 
AST(SGOT)/ALT(SGPT) 
 
≤3 × institutional ULN 
− 
glomerular filtration rate (GFR) ≥40 mL/min/1.73 m2 by the Cockcroft-Gault 
formula (see Appendix B) 
 
 
3.1.6 Patients must meet the following minimum wash-out window from previous treatments 
to the first treatment 
• ≥3 weeks for systemic anti-cancer therapies  
• ≥2 weeks for phototherapy, local radiation therapy, topical high potency 
corticosteroid, topical retinoid, topical nitrogen mustard, or topical toll-like receptor 
(TLR)-agonist 
• ≥12 weeks for total skin electron beam therapy 
Participants with rapidly progressive malignant disease may be enrolled prior to 
completion of the above periods with approval of the protocol director. 
 
3.1.7 Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral 
therapy with undetectable viral load within 6 months are eligible for this trial. 
 
3.1.8 For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral 
load must be undetectable on suppressive therapy, if indicated. 
 
3.1.9 Patients with a history of hepatitis C virus (HCV) infection must have been treated and 
cured.  For patients with HCV infection who are currently on treatment, they are eligible 
if they have an undetectable HCV viral load. 
 
3.1.10 Patients with treated brain metastases are eligible if follow-up brain imaging after 
central nervous system (CNS)-directed therapy shows no evidence of progression for a 
minimum of 3 months.   
 
3.1.11 Patients with a prior or concurrent malignancy whose natural history or treatment does 
not have the potential to interfere with the safety or efficacy assessment of the 
investigational regimen are eligible for this trial. 
 
3.1.12 The effects of Hu5F9-G4 (magrolimab) on the developing human fetus are unknown.  
For this reason and because monoclonal antibody agents as well as other therapeutic 
agents used in this trial (mogamulizumab) are known to be teratogenic, women of child-
bearing potential and men must agree to use adequate contraception (hormonal or barrier 
method of birth control; abstinence) prior to study entry and for the duration of study 
participation and continue for 4 months after the last dose of both Hu5F9-G4 
(magrolimab) and mogamulizumab.  Effective contraception is defined as oral 
contraceptives, double barrier method (condom plus spermicide or diaphragm plus 
spermicide) or practice true abstinence from heterosexual intercourse.  Women of 
childbearing potential includes any female who has experienced menarche and has not 
undergone successful surgical sterilization or is not postmenopausal (defined as 

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26 
amenorrhea ≥12 consecutive months).  Should a woman become pregnant or suspect she 
is pregnant while she or her partner is participating in this study, she should inform her 
treating physician immediately.  Men treated or enrolled on this protocol who are 
sexually active with women of childbearing potential and who have not had vasectomies 
must also agree to use adequate contraception prior to the study, for the duration of study 
participation, and 4 months after completion of Hu5F9-G4 (magrolimab) administration. 
 
3.1.13 Female patients of childbearing potential must not be nursing or planning to be pregnant 
and must have a negative urine or serum pregnancy test within 30 days before 
randomization and within 72 hours before the first administration of study treatment. 
 
• Female patients of childbearing potential must be willing to use one highly 
effective method of contraception during the study and continue for 4 
months after the last dose of study treatment. 
 
• Male patients who are sexually active with a woman of childbearing 
potential (WOCBP) and who have not had vasectomies must be willing to 
use a barrier method of contraception (condom plus spermicidal gel) and 
refrain from sperm donation during the study and for 4 months after the 
last dose of study treatment.  If the partner is pregnant, male patients must 
use barrier method contraception (condom) during the study and for 4 
months after the last dose of study treatment to prevent fetal exposure to 
study treatment. 
 
3.1.14 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. 
 
3.1.15 Willing to comply with clinic visit schedule and procedures including mandatory biopsies 
 
3.2 
Exclusion Criteria 
 
3.2.1 Prior treatment with Hu5F9-G4 (magrolimab) or any agent targeting CD47-SIRPα 
 
3.2.2 Prior progression of disease with mogamulizumab  
 
3.2.3 Patients who have not recovered from adverse events due to prior anti-cancer therapy 
(i.e., have residual toxicities > Grade 1) with the exception of alopecia and lymphopenia 
(any grade permitted).  Residual peripheral neuropathy must have improved to grade 2 or 
better.    
 
3.2.4 Patients who are receiving any other investigational agents. 
 
3.2.5 Allogeneic hematopoietic stem cell transplant recipients with any graft-versus-host 
disease within the previous 3 months or requiring immunosuppression 
 

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27 
3.2.6 Active autoimmune disease that has required systemic immunosuppressive medication 
within the previous 3 months 
 
3.2.7 Active herpes simplex or herpes zoster.  Subjects on prophylaxis for herpes who have no 
active signs of active infection, and whose last active infection was more than 6 months 
ago, may enter the study, and should continue to take the prescribed medication for the 
duration of the study 
 
3.2.8 History of allergic reactions attributed to compounds of similar chemical or biologic 
composition to Hu5F9-G4 (magrolimab), other monoclonal antibodies, or other agents 
(mogamulizumab) used in study. 
 
3.2.9 Significant cardiopulmonary disease defined as  
a. Acute myocardial infarction within the last 6 months 
b. Unstable angina  
c. Congestive heart failure NYHA Class III-IV 
 
3.2.10 Patients with uncontrolled intercurrent illness requiring antibiotics.  Patients on 
prophylactic antibiotics for non-complicated staphylococcus colonization/infection are 
eligible. 
 
3.2.11 Patients with new or progressive brain metastases (active brain metastases) or 
leptomeningeal disease are excluded. 
 
3.2.12 Patients with psychiatric illness/social situations or substance abuse that would limit 
compliance with study requirements. 
 
3.2.13 Pregnant women are excluded from this study because Hu5F9-G4 (magrolimab) is 
monoclonal antibody 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 Hu5F9-G4 (magrolimab), breastfeeding should 
be discontinued if the mother is treated with Hu5F9-G4 (magrolimab).  These potential 
risks may also apply to other agents used in this study (mogamulizumab). 
 
3.2.14 Patients with RBC transfusion dependence, defined as requiring more than 2 units of 
RBCs transfused during the 4-week period prior to screening.  RBC transfusions are 
permitted during the screening period and prior to enrollment. 
 
3.2.15 Patients with prior autoimmune thrombocytopenia, hemolytic anemia or Evans Syndrome 
requiring treatment in the last 12 months. 
 
3.2.16 Patients on the following medications at the time of enrollment: 
• Immunotherapy or immunosuppressive drugs (e.g. chemotherapy or systemic 
corticosteroids) EXCEPT for the following:  
o Intranasal, inhaled, or local steroid injection (e.g. intra-articular injection) 
o Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or 

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28 
equivalent, if patient has been on a stable dose for at least 2 weeks prior to the 
first treatment 
o Low and medium potency topical corticosteroids are permitted if patient has 
been on a stable dose for at least 2 weeks prior to the first treatment 
o Steroids as premedication for hypersensitivity reactions (e.g. CT scan 
premedication). 
• Growth factors (granulocyte colony stimulating factor or granulocyte macrophage 
colony stimulating factor) EXCEPT for erythropoietin and darbepoietin alpha. 
• Herbal remedies with immunostimulating properties (e.g., mistletoe extract) or known 
to potentially interfere with major organ function (e.g. hypericin). 
 
3.2.17 Live vaccines are not allowed while participating in the trial.  Examples of live vaccines 
include, but are not limited to, the following:  measles, mumps, rubella, chicken pox, 
yellow fever, rabies, Bacillus Calmette–Guérin (BCG), typhoid (oral) vaccine, and 
intranasal influenza vaccines (e.g., Flu-Mist®).  However, seasonal influenza vaccines 
for injection are generally killed virus vaccines and are allowed.  
 
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 subjects or the purpose of the research.  Exclusion under other 
circumstances must be designated by the Director, NIH, upon the recommendation of an IC 
Director based on a compelling rationale and justification.  Cost is not an acceptable reason for 
exclusion except when the study would duplicate data from other sources.  Women of 
childbearing potential should not be routinely excluded from participation in clinical research.  
Please see http://grants.nih.gov/grants/funding/phs398/phs398.pdf. 
 
 
4. REGISTRATION PROCEDURES 
 
4.1 
Investigator and Research Associate Registration with CTEP 
 
Food and Drug Administration (FDA) regulations require sponsors to select qualified 
investigators.  National Cancer Institute (NCI) policy requires all individuals contributing to 
NCI-sponsored trials to register with their qualifications and credentials and to renew their 
registration annually.  To register, all individuals must obtain a Cancer Therapy Evaluation 
Program (CTEP) credentials necessary to access secure NCI Clinical Oncology Research 
Enterprise (CORE) systems.  Investigators and clinical site staff who are significant contributors 
to research must register in the Registration and Credential Repository (RCR) at 
https://ctepcore.nci.nih.gov/rcr/. The RCR is a self-service online person registration application 
with electronic signature and document submission capability. 
 
RCR utilizes five person registration types. 

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30 
 
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 IRBManager 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 for the site to be able to have an Approved status following processing of the 
IRB/REB approval record: 
• Have an active CTEP status, 
• Have an 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, be active on the NCI CIRB roster under the applicable CIRB 
Signatory Institution(s) record, 
• Include the IRB number of the IRB providing approval in the FDA Form 1572 in the RCR 
profile,  
• List all sites on the IRB/REB approval as Practice Sites in the FDA Form 1572 in the 
RCR profile; and 
• Have the appropriate CTEP registration type for the protocol.  
 
Additional Requirements 
 
Additional 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 applicable 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: 
 
• Log in to the CTSU members’ website (https://www.ctsu.org) 
• Click on Protocols in the upper left of the screen 

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31 
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-CA043, and 
protocol number 10384, 
• Click on Documents, Protocol Related Documents, and use the Document Type filter and 
select Site Registration, to 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 10384 Site Registration 
 
• 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.  Users are strongly encouraged to take a refresher of the 
training if they have not entered specimen data for an extended period of time. 
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). 
 
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 
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 

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32 
the DTL are available in the Help Topics button in the DTL application and describe DTL task 
assignments, CI signature, and CTEP registration requirements, as well as include a Master Task 
List. 
 
4.2.4 Checking Site Registration Status 
 
Site’s registration status may be verified on the CTSU members’ 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 
 
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:   
 
• Active CTEP registration with the credentials necessary to access secure NCI/CTSU IT 
systems; 
• 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 Delegation of Tasks Log (DTL) is required for the study, the registrar(s) 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 
FDA Form 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. 
 

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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 
conjunction with patient enrollment 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.  
 
4.3.2 Special Instructions for Patient Enrollment 
 
1. Site staff with the appropriate roles will reserve slots using IWRS (https://open.ctsu.org/). 
2. City of Hope Cancer Center will receive notification via the IWRS when a slot has been 
reserved.  An e-mail will be sent from the City of Hope Cancer Center to the site 
requesting further information such as:  patient initials, tumor type, and potential start 
date.  The spot will show as ‘pending approval’ in the system until the site sends a 
REGISTRATION FORM/ELIGIBILITY CHECKLIST accompanied with documents 
supporting eligibility (signed consent, baseline labs, pathology reports, bone marrow 
reports, CT or x-ray reports, and latest clinic note) to the City of Hope Cancer Center at 
ccc@coh.org for review and confirmation of eligibility. 
3. Once the registration has been reviewed, the City of Hope Cancer Center will either 
approve or disapprove the request depending on confirmation of patient eligibility.  If 
approved, the City of Hope Cancer Center will update the spot to ‘reserved’ in IWRS. 
4. The site can now enroll the patient into the study in OPEN. 
 
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 Early-Phase 
and Experimental Clinical Trials Biospecimen Bank (EET Biobank, formerly known as 
the ETCTN Biorepository).   

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anatomic pathology report must be sent with the tissue to the EET Biobank. 
 
 
5.2 
Specimen Procurement Kits and Scheduling 
 
5.2.1 Specimen Procurement Kits  
 
Kits for the collection and shipment of skin punches in formalin to the EET Biobank can be 
ordered online via the Kit Management system: (https://kits.bpc-apps.nchri.org/).  
 
Users at the clinical sites will need to set up an account in the Kit Management system and select 
a specific clinical trial protocol to request a kit.  Please note that protocol may include more than 
one type of kit.  Each user may order two kits per kit type per day (daily max = 6 kits).  Kits are 
shipped ground, so please allow 5-7 days for receipt.  A complete list of kit contents for each kit 
type is located on the Kit Management system website. 
 
Note:  Kits or supplies are only provided for specimens shipped to the Biobank. Institutional 
supplies must be used for all other specimen collection and processing.  
 
5.2.2 Scheduling of Specimen Collections 
 
Please adhere to the following guidelines when scheduling procedures to collect tissue:  
• Tumor tissue specimens collected during biopsy procedures and fixed in formalin must 
be shipped on the same day of collection. 
• Tissue in formalin can be collected Monday through Wednesday and shipped overnight 
for arrival on Tuesday through Thursday at the EET Biobank at Nationwide Children’s 
Hospital. 
• Fresh blood specimens may be collected and shipped Monday through Friday.  
• Specimens submitted frozen (e.g. serum) can be collected on any day but must be stored 
frozen and shipped to the EET Biobank on Monday through Thursday.  In the event that 
frozen specimens cannot be shipped immediately, they must be maintained in a -70°C to -
80°C freezer. 
 
5.3 
Specimen Tracking System Instructions 
 
5.3.1 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: 

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o Patients must provide a signed and dated, written informed consent form. 
 
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. 
 
5.3.2 Specimen Labeling 
 
5.3.2.1 Blood Specimen Labels  
 
Include the following on 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) 
• Collection date (to be added by hand) 
 
5.3.2.2 Tissue Specimen Labels  
 
Include the following on all tissue specimens or containers (e.g., formalin jar):  
• Patient Study ID 
• Universal Patient ID (UPID) 

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• Specimen ID (automatically generated by Rave) 
• Time point 
• Specimen type (e.g., formalin-fixed paraffin-embedded [FFPE] Block, Formalin 
Fixed Tissue, Fresh Tissue in Media, etc.) 
• Biopsy site 
• Surgical pathology ID (SPID) number (when applicable)  
• Block number from the corresponding pathology report (archival only) 
• Collection date and time (to be added by hand)  
• Slide section number (only if archival tissue is submitted as slides) (to be added by 
hand) 
 
5.3.2.3 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. 
 
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 
 

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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. 
 
5.3.3 Overview of Process at Treating Site 
 
5.3.3.1 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 without eligibility specimen analysis:  
 
1. Site enters registration data into OPEN during one or more steps. 
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 all applicable registration data directly to Rave at the end of the final 
registration step. 
 
Any data entry errors made during enrollment should be corrected in Rave. 
 
5.3.3.2 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 and 
collect specimen. 
• Label specimen containers and write collection date [if the study also requires recording 
the collection time on the label, include the time] on each label.  After collection, store 
labeled specimens as described in Section 5.3.2. 
• Apply an extra specimen label to each report before scanning.  Return to the Histology 
and Disease form to upload any initial Pathology, Radiology, Molecular Reports (up to 
4), Surgical (or Operative) reports and Tissue Biopsy Verification form (when 
applicable).  Return to Specimen Tracking Enrollment CRF to upload any molecular 
report (one per specimen) and/or specimen specific pathology or related report (one per 

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specimen).  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 (either by 
adding a label or hand writing).  
 
Step 3:  Complete specimen data entry. 
• 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. 
 
5.4 
Specimen Collection  
 
5.4.1 Archival or Formalin-Fixed Paraffin-Embedded (FFPE) Tumor Specimen  
 
If previously-collected FFPE tissue will be submitted, then the following criteria must be met: 
 
• Tissue must have been collected within 6 months prior to registration or any time after 
registration 
• FFPE tumor tissue block(s) must be submitted.  The optimal block is at least 70% tumor.  
Specimen size requirement is as follows: 
o Surface area:  25 mm2 is optimal.  Minimum is 5 mm2. 
o Volume:  1 mm3 optimal.  Minimum volume is 0.2 mm3, however the success of 

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DNA extraction decreases at suboptimal tissue volume. 
 
If an existing block cannot be submitted, the following are requested, if available: 
• One (1) H&E slide (3-5 µm) 
• Five (5) 3-5 µm unstained air-dried charged slides 
• Thirty (30) 10 µm unstained air-dried uncharged slides  
 
Process and number slides sequentially (e.g., H&E stained slide should be created first and 
labeled with “1,” and additional unstained slides should be processed next and be labeled 2 – n). 
 
See Section 5.3.2 for labeling instructions. 
 
5.4.2 Formalin-Fixed Skin Punch Biopsies  
 
1. Label formalin-filled containers according to instructions in Section 5.3.2.  
2. Obtain two ≥5mm punch biopsies, and place one punch in each cassette.  
3. Snap the cassette lids closed and place cassettes into pre-labeled container(s) (one 
container per biopsy site) filled with 10% neutral buffered formalin as soon as possible 
after collection to prevent air drying.  Samples should be fixed for 3-72 hours. 
4. Secure the container lids and package containers into the shipping kit according to 
instructions in Section 5.5.  Keep tissue in formalin jars at room temperature until 
shipment to the EET Biobank.  
 
5.4.3 Blood Collection  
 
5.4.3.1 Collection of Blood in Sodium Heparin Tubes for Whole Blood Processing  
 
1. Label Sodium Heparin tubes according to the instructions in Section 5.3.2. 
2. Collect specified volume of blood per timepoint (see Section 5.1) in Sodium Heparin 
tubes and gently invert tubes to mix. 
3. Ship on day of collection (whenever possible) according to instructions in Section 
5.5. 
4. If blood cannot be shipped on the day of collection (e.g., a late scheduled collection), 
then refrigerate until shipment.  
 
5.4.3.2 Collection of Blood in Red Top Tubes for Serum Processing  
 
1. Collect specified volume of blood per timepoint (see Section 5.1) in a Red Top Serum 
tube and gently invert tubes 8-10 times to mix.  
2. Place the Red Top tube upright.  Allow 30 minutes of clotting time at room 
temperature. 
3. Centrifuge Red Top tube for 10-15 minutes at 1,000-1,300 RCF (g) in a swing bucket 
centrifuge. 
4. Label cryovials according to the instructions in Section 5.3.2. 
5. Transfer equal aliquots of the serum layer to 4 cryovials.   
6. Cap cryovials and place immediately upright on ice.  Freeze immediately at -70˚ or 

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colder until shipment.   
 
 
5.5 
Shipping Specimens from Clinical Site to the EET Biobank  
 
5.5.1 General Shipping Information 
 
Skin punch biopsies that are fixed in formalin and fresh blood should be shipped at ambient 
temperature the day of collection.  For skin punch biopsies, the Tissue Biopsy verification form 
is required both in the package and uploaded in the ETCTN specimen tracking system.  In winter 
months, please include extra insulation, such as bubble wrap, inside the shipping container. 
 
For all archival tissue, the corresponding anatomical clinical pathology report is required both in 
the package and uploaded in the ETCTN specimen tracking system.  If this is not available at the 
time of shipment, then it must be sent to the EET Biobank as soon as possible and uploaded to 
the ETCTN specimen tracking system, or the specimen will not be processed.  The pathology 
report must state the disease diagnosis made by the reviewing pathologist. 
 
5.5.1.1 Required Forms for Specimen Submissions: 
 
Each document submitted with the specimen must be labeled with a label printed from the STS, 
or the Universal ID and Patient Study ID.  
 
Tissue  
Required Forms 
Archival 
1. Shipping List 
2. Corresponding Pathology Report 
 
Skin punch biopsies in formalin 
1. Shipping List 
2. Tissue Biopsy Verification Form 
3. Diagnostic Pathology Report  
4. Surgical and/or Radiology Report 
Blood 
1. Shipping List 
 
 
5.5.2 Specimen Shipping Instructions 
 
Tissue in formalin must be shipped on the day of collection.  Collect and ship on Monday 
through Wednesday. 
 
Frozen specimens and archival (FFPE) tissue may be shipped on Monday through Thursday. 
 
Fresh blood may be shipped on Monday through Friday.  Please select “Saturday Delivery” 
when shipping fresh blood on a Friday.  

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5.5.2.1 
Shipping of FFPE Blocks and Glass Slides  
 
1. Before packaging blocks or slides, verify that each specimen is labeled according to 
Section 5.3.2.2. 
2. Blocks should be placed in a hard-sided container, preferably a special block holder, to 
protect the specimen.  Glass slides are to be placed in plastic slide holders.  Place tissue 
paper on top of the separated slides prior to closing the slide holder to reduce slide 
movement during shipment. 
3. Place the blocks or slides in a reinforced cardboard shipping box with appropriate 
packaging filler to minimize movement of specimens within the shipping box. 
4. Include a copy of the forms listed above and a shipping manifest from the Specimen 
Tracking System with each shipment.  
5. Please include a cold pack when shipping on hot days and extra insulation on cold days. 
Ship specimens to the address listed below.  FedEx Priority Overnight is strongly recommended 
to prevent delays in package receipt. 
 
5.5.2.2 Shipping Ambient Blood Using Institutional Supplies (kits are not provided).  
 
1. Before packaging specimens, verify that the collection tube is labeled according to 
instructions in section 5.3.2.1. 
2. Place the blood collection tube into a zip-lock bag.   
3. Place zip-lock bag into a biohazard envelope with absorbent material.  Expel as much air 
as possible and seal the envelope securely.  
4. Place the biohazard envelope into a Tyvek envelope.  Expel as much air as possible and 
seal securely. 
5. Place the specimen(s) and a copy of the shipping manifest into a sturdy shipping 
container. In winter months, please use an insulated container and include extra 
insulation, such as bubble wrap, inside the shipping container to prevent specimens from 
freezing.  
6. Close the container and tape shut. 
7. Attach a shipping label to the top of the shipping container.  
8. Attach an Exempt Human Specimen sticker to the side of the container. 
9. Ship specimens via overnight courier to the address below.  FedEx Priority Overnight is 
strongly recommended to prevent delays in package receipt. 
 
 
5.5.2.3 Shipping Frozen Specimens Using Supplies Provided by the Institution 
 
1. Before packaging specimens, verify that each specimen is labeled according to the 
instructions in 5.3.2 and that lids of all primary receptacles containing liquid are tightly 
sealed.  
2. Place the specimens in zip-lock bags.  Use a separate zip-lock bag for each specimen type 
and time point.  
3. Place the zip-lock bags in a biohazard envelope containing absorbent material.  Expel as 
much air as possible and seal securely.  

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4. Put the secondary envelope into a Tyvek envelope.  Expel as much air as possible and 
seal securely.  
5. Place frozen specimens into the insulated shipping container with dry ice.  Layer the 
bottom of the container with dry ice until it is approximately one-third full.  Place the 
frozen specimens on top of the dry ice.  Cover the specimens with the dry ice until the 
container is almost completely full.  When packaging specimens, ensure that you leave 
enough room to include at least 5 pounds of dry ice in the shipment.  
6. Insert a copy of the required forms into a plastic bag and place in the shipping container. 
7. Close the shipping container and tape it shut with durable sealing tape.  Do not 
completely seal the container. 
8. Complete a FedEx air bill and attach to top of shipping container. 
9. Complete a dry ice label. 
10. Attach the dry ice label and an Exempt Human Specimen sticker to the side of the 
shipping container. 
11. Ship specimens via overnight courier to the address below.  FedEx Priority Overnight is 
strongly recommended to prevent delays in package receipt.  
 
5.5.2.4 Shipping Ambient Tissue and Blood in a Single-Chamber Kit  
 
Blood in sodium heparin may be shipped in the kit with the tissue in formalin when collected on 
the same day. 
 
1. Before packaging specimens, verify that each specimen is labeled according to the 
instructions above Section 5.3.2 and that the lids of all primary receptacles containing 
liquid are tightly sealed.  The lids of formalin jars should be wrapped in parafilm.  
Absorbent material must be placed around each primary container that holds liquid. 
2. Place the specimens in zip-lock bags.  Use a separate bag for each specimen type. 
3. Place specimens into the secondary pressure vessel surrounded by bubble wrap.  Place 
the lid on the secondary pressure vessel and set it inside the kit chamber. 
4. Place a copy of the shipping manifest and corresponding reports such as pathology, 
surgical, or radiology reports into the insulated shipping container. 
5. Set the lid on top of the container.  Close the outer flaps and tape shut. 
6. Attach a shipping label to the top of the shipping container. 
7. Attach an Exempt Human Specimen sticker to the side of the container. 
8. Ship specimens via overnight courier to the address below.  FedEx Priority Overnight is 
strongly recommended to prevent delays in package receipt.  
 
 
5.5.3 Shipping Address 
 
Ship to the address below.  Ship formalin-fixed and fresh blood specimens the same day of 
specimen collection.  Do not ship specimens the day before a holiday. 
 
EET Biobank 
The Research Institute at Nationwide Children's Hospital 
700 Children's Drive, WA1340 

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45 
Columbus, Ohio 43205 
PH: (614) 722-2865 
FAX: (614) 722-2897 
Email: BPCBank@nationwidechildrens.org 
 
FedEx Priority Overnight service is very strongly preferred.   
 
NOTE:  The EET Biobank FedEx Account will not be provided to submitting institutions.  
There is no central courier account for this study.  Sites are responsible for the cost of shipments 
to the EET Biobank. 
 
5.5.4 Contact Information for Assistance 
 
For all queries, please use the contact information below: 
 
EET Biobank 
Toll-free Phone:  (800) 347-2486 
E-mail:  BPCBank@nationwidechildrens.org 
 
 
5.6 
Biomarker Plan  
Note for participating sites: Please see Section 5.1 for details on specimens to collect.  The 
specimens tested are not always the same specimens that are submitted by the site, as processing 
of blood and tissue will occur at the Biobank prior to testing.

 
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5.7 
Integrated Correlative Studies 
 
5.7.1 CCR4 expression 
 
5.7.1.1 Specimen(s) Receipt and Processing at the EET Biobank  
 
EET Biobank will receive skin punch biopsy fixed in formalin at baseline, Cycle 1 Week 2, 
Cycle 3 Week 3, and end of treatment or progression.  Samples should be processed to FFPE 
blocks within 72 hours of fixation.  Five unstained sections, 3-4 micron, on charged slides will 
be used for this assay.  
 
5.7.1.2 Site(s) Performing Correlative Study 
 
This assay will be performed at MSKCC Pathology under the supervision of Ahmet Dogan, 
M.D., Ph.D.  Archival tissue may be analyzed if available, but this does not replace the analysis 
of the formalin fixed skin biopsies collected at baseline, Cycle 1 Week 2, Cycle 3 Week 3, and 
end of treatment or progression.   
 
5.7.1.3 Contact information for notification of specimen shipment 
 
MSKCC Pathology 
Ahmet Dogan, M.D., Ph.D.  
dogana@mskcc.org 
 
5.8 
Exploratory/Ancillary Correlative Studies 
 
5.8.1 Spatial association of tumor cells and components of the tumor microenvironment 
including macrophage enumeration and phenotyping 
 
5.8.1.1 Specimen(s) Receipt and Processing at the EET Biobank  
 
EET Biobank will receive skin punch biopsy fixed in formalin at baseline, Cycle 1 Week 2, 
Cycle 3 Week 3, and end of treatment or progression.  Samples should be processed to FFPE 
blocks within 72 hours of fixation.  Blocks should be shipped to the Nolan Laboratory after 
slides have been cut for the CCR4 expression assay (see Section 5.7.1). 
 
5.8.1.2 Site(s) Performing Correlative Study 
 
This assay will be performed at Nolan Laboratory, Stanford University, under the supervision of 
Garry Nolan, Ph.D. 
 
5.8.1.3 Contact information for notification of specimen shipment 
 
Nolan Laboratory, Stanford University 
Garry Nolan, Ph.D. 

 
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gnolan@stanford.edu 
 
5.8.2 Whole Exome Sequencing 
 
5.8.2.1 Specimen(s) Receipt and Processing at the EET Biobank 
 
FFPE tissue blocks will be sectioned to generate an initial hematoxylin and eosin (H&E)-stained 
slide.  All H&E stained slides will undergo a pathology QA review and annotation for 
macrodissection.  Following macrodissection, tumor tissue from unstained slides will be scraped 
for co-extraction of DNA and RNA.  The nucleic acids will be analyzed to determine 
concentration and quality.  DNA will be shipped to the central sequencing laboratory for 
analysis. 
 
For collection of germline DNA, blood will be collected in Green Top tubes at baseline or at the 
time of lowest peripheral blood Sezary cell percentage.  Samples should be processed by Ficoll 
gradient purification to isolate PBMCs.  PBMCs will be cryopreserved in cryovials and stored in 
liquid nitrogen vapor phase freezer.  Cryopreserved PBMCs collected at baseline or at the time 
of the lowest leukemic disease will be shipped from the EET Biobank to the Khodadoust 
laboratory.  CD4 depletion will be performed at the Khodadoust Laboratory, Stanford 
University, under the supervision of Michael Khodadoust, M.D. Ph.D.  PBMCs will be depleted 
of CD4-expressing cells and DNA will be extracted. DNA will be quantitated, and then stored in 
a -80°C freezer until shipping to the NCLN Genomics Laboratory for analysis. 
 
5.8.2.2 Site(s) Performing Correlative Study   
 
This assay will be performed at the NCLN Genomics Laboratory under the supervision of 
Mickey Williams, Ph.D.   
 
5.8.2.3 Shipment of Specimens from the EET Biobank to Site Performing Correlative Study 
 
DNA will be shipped from the EET Biobank to: 
NCLN Genomics Laboratory at The University of Texas MD Anderson Cancer Center 
Attn: Jincy Veliyathu or Khushali Rajendra Patel 
Zayed Building 
CTLU Z3.4020 
6565 MD Anderson Blvd 
Houston, TX 77030 
 
Blood Specimens will be shipped from the EET Biobank to: 
 
Stanford University/Khodadoust Laboratory 
Attn:  George Duran  
1701 Page Mill Road, Suite #271  
Palo Alto, CA 94304  
650-725-6420 
georgedu@stanford.edu 

 
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5.8.2.4 Contact information for Notification of Specimen Shipment 
 
DNA and Blood:  Thomas Forbes (NCLNGenomicsReceiving@nih.gov) 
Blood:  George Duran (georgedu@stanford.edu)  
 
5.8.3 RNAseq 
 
5.8.3.1 Specimen(s) Receipt and Processing at the EET Biobank 
 
FFPE tissue blocks will be sectioned to generate an initial hematoxylin and eosin (H&E)-stained 
slide.  All H&E stained slides will undergo a pathology QA review and annotation for 
macrodissection.  Following macrodissection, tumor tissue from unstained slides will be scraped 
for co-extraction of DNA and RNA.  The nucleic acids will be analyzed to determine 
concentration and quality.  RNA will be shipped to the central sequencing laboratory for 
analysis. 
 
5.8.3.2 Site(s) Performing Correlative Study 
 
See Section 5.8.2.2 for details. 
 
5.8.3.3 Shipment of Specimens from the EET Biobank to Site Performing Correlative Study 
 
Specimens will be shipped from the EET Biobank to: 
NCLN Genomics Laboratory at The University of Texas MD Anderson Cancer Center 
Attn: Jincy Veliyathu or Khushali Rajendra Patel 
Zayed Building 
CTLU Z3.4020 
6565 MD Anderson Blvd 
Houston, TX 77030 
 
5.8.3.4 Contact Information for Notification of Specimen Shipment 
 
Thomas Forbes (NCLNGenomicsReceiving@nih.gov)  
 
5.8.4 Phagocytosis Index 
 
5.8.4.1 Specimen(s) Receipt and Processing at the EET Biobank 
 
Blood will be collected in Green Top tubes at baseline and end of treatment or progression.  
Samples should be processed by Ficoll gradient purification to isolate PBMCs.  PBMCs will be 
cryopreserved in cryovials and stored in liquid nitrogen vapor phase freezer. 
 
5.8.4.2 Site(s) Performing Correlative Study   
 
This assay will be performed by the Weinstock Laboratory at the Dana-Farber Cancer Institute 

 
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under the supervision of David Weinstock, M.D., and Salvia Jain, M.D. 
 
5.8.4.3 Contact information for notification of specimen shipment 
 
Weinstock Laboratory, Dana-Farber Cancer Institute  
David Weinstock MD and Salvia Jain MD 
Davidm_weinstock@dfci.harvard.edu 
ssjain@bidmc.harvard.edu   
 
5.8.5 Immunophenotyping of circulating tumor cells 
 
5.8.5.1 Specimen(s) Receipt and Processing at the EET Biobank 
 
Blood will be collected in Green Top tubes at baseline and end of treatment or progression.  
Samples should be processed by Ficoll gradient purification to isolate PBMCs.  PBMCs will be 
cryopreserved in cryovials and stored in liquid nitrogen vapor phase freezer. 
 
5.8.5.2 Site(s) Performing Correlative Study   
 
This assay will be performed by the Khodadoust Laboratory and Stanford HIMC under the 
supervision of Michael Khodadoust, MD., Ph.D. 
 
5.8.5.3 Contact information for notification of specimen shipment 
 
Khodadoust Laboratory and Stanford HIMC  
Michael Khodadoust MD PhD 
mkhodado@stanford.edu  
George Duran 
georgedu@stanford.edu   
 
5.8.6 T cell receptor sequencing 
 
5.8.6.1 Specimen(s) Receipt and Processing at the EET Biobank 
 
Blood will be collected in Green Top tubes at baseline, Cycle 1 Week 2, Cycle 3 Week 3, Cycle 
6 Week1, and end of treatment or progression.   Samples should be processed by Ficoll gradient 
purification to isolate PBMCs.  PBMCs will be cryopreserved in cryovials and stored in liquid 
nitrogen vapor phase freezer. 
 
5.8.6.2 Site(s) Performing Correlative Study 
 
This assay will be performed at Adaptive Biotechnologies. 
 
5.8.6.3 Contact information for notification of specimen shipment 
 
Adaptive Biotechnologies. 

 
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5.8.7 Anti-drug antibody detection 
 
5.8.7.1 Specimen(s) Receipt and Processing at the EET Biobank 
 
Serum will be collected and aliquoted into cryovials by participating sites at baseline, Cycle 1 
Week 2, Cycle 3 Week 3, Cycle 6 Week1, and end of treatment or progression.  Frozen cryovials 
will be shipped to the EET Biobank and then stored in a -80°C freezer until shipping to Gilead 
Sciences for analysis.   
 
5.8.7.2 Site(s) Performing Correlative Study 
 
This assay will be performed at Gilead Sciences. 
 
5.8.7.3 Contact information for notification of specimen shipment 
 
Gilead Sciences. 
 
 
6. TREATMENT PLAN 
 
Hu5F9-G4 (magrolimab) binds to red blood cells and leads to erythrophagocytosis.  During the 
screening period prior to initiation of Hu5F9-G4 (magrolimab) therapy, blood cell ABO 
phenotyping for minor antigens, type and screen (ABO/Rh), and Direct Antiglobulin Test (DAT) 
should be performed for each patient.  This will facilitate allocation of properly cross-matched 
blood, should a blood transfusion be warranted (see Section 7.1.3). 
 
6.1 
Agent Administration 
 
Treatment will be administered on an outpatient basis.  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 intent to treat the patient's malignancy. 
 
Hu5F9-G4 (magrolimab) dose will be calculated using the actual body weight of the patient at 
enrollment, and the dose may remain constant throughout the study unless a greater than 10% 
change in weight is observed. 
 
All study patients will start Hu5F9-G4 (magrolimab) priming dose at 1 mg/kg IV followed by 
30 mg/kg IV once a week in the first 2 cycles on a 28-day cycle.  In cycle 3 and subsequent 
cycles, study patients will receive 30 mg/kg IV every 2 weeks on a 28-day cycle (see Table 2 
below).   
 
Hu5F9-G4 (magrolimab) may interfere with the assessment of RBC phenotyping.  Hu5F9-G4 
(magrolimab) binds to CD47 on RBCs and can mask detection of antibodies to minor antigens to 
the patient’s RBC and ABO/Rh phenotype, DAT and Ab screen. 

 
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Before Starting Hu5F9-G4 (magrolimab), 
• The following assessments must be performed and resulted. 
o ABO/Rh type and screen, 
o Antibody Screen, 
o DAT 
o Extended RBC phenotyping including minor antigens such as CcDEe, Cw, 
MNSs, Kk, FyaFyb, and Jka Jkb 
o RBC genotyping must be performed if a patient received any RBC or whole blood 
transfusion within the previous 3 months (unless laboratory has availability for 
special techniques for performing phenotyping for patients with recent 
transfusion).  This may be performed for all patients in lieu of an extended RBC 
phenotyping. 
• Ensure that the patient is provided a Patient Information Card containing their pre-study 
blood typing. 
 
Hemoglobin must be ≥9.0 g/dL within 24 hours prior to the first 2 doses of Hu5F9-G4 
(magrolimab) infusion.  If several hemoglobin tests are performed prior to Dose 1 and Dose 2, 
the closest to the infusion should be considered.  RBC transfusions are allowed to meet the 
minimum hemoglobin requirement prior to the first 2 doses. 
 
Please refer to Section 7.1.4 for instructions for monitoring for anemia and anemia symptoms 
post-infusion. 
 
 

 
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Table 2: Dose De-escalation Schedule for Phase 1b 
Dose De-escalation Schedule 
Dose Level 
Premedications: 
Precautions 
Dose 
Cycle 
Length 
Hu5F9-G4 
(Magrolimab) 
Mogamulizumab 
 
Level 1 (starting dose 
level) 
650-1,000 mg 
acetaminophen 
oral (PO) and 25 
mg 
diphenhydramine 
(PO or IV) or a 
comparable 
regimen at least 
15 minutes before 
the first two 
doses of Hu5F9-
G4 
1 mg/kg IV priming 
dose; Then 30 mg/kg 
IV weekly in Cycles 
1 & 2 followed by 
Q2W ≥ Cycle 3). 
Give before 
mogamulizumab. 
1 mg/kg IV 
(weekly for cycle 
1, then Q2W 
starting from cycle 
2) 
28 Days 
Level -1 
Same as level 1 
1 mg/kg IV priming 
dose; Then 20 mg/kg 
IV weekly in Cycles 
1 & 2, followed 
byQ2W ≥ Cycle 3). 
Give before 
mogamulizumab. 
1 mg/kg IV 
(weekly for cycle 
1, then Q2W 
starting from cycle 
2) 
28 Days 
Q2W = Every 2 weeks, IV = Intravenous 
*Priming dose will be given one week before Cycle 1 over 3 hours (+/- 30 minutes) 
**Hu5F9-G4 (magrolimab) to be administered before mogamulizumab on days when both 
treatments are given 
*** Within 24 hours prior to each of the first 2 doses of Hu5F9-G4infusion, patients must have a 
documented hemoglobin level of ≥9 g/dL.  Patients who do not meet these criteria must be transfused 
and have their hemoglobin rechecked to meet the minimum hemoglobin threshold prior to 
administering each of the first 2 doses of Hu5F9-G4.  An additional hemoglobin must be checked 3 to 
6 hours after the initiation of the first and second doses of Hu5F9-G4. The patient should be 
transfused as clinically appropriate.  Investigators should consider additional hemoglobin monitoring 
during the first week of treatment in patients with symptoms of anemia or at increased risk for 
complications of anemia. 
 
 
As of the July 2023 amendment, the phase 1b portion has been completed with an enrollment of 
6 patients at dose level 1.  Out of the 6 patients treated, 1 experienced a DLT.  The recommended 
phase 2 dose (RP2D) has been established as dose level 1 (30mg/kg magrolimab starting cycle 
1). 
 

 
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Table 3: Regimen Description for Phase 2 (Hu5F9-G4 (magrolimab) + Mogamulizumab Arm) 
Regimen Description 
Agent 
Premedications; 
Precautions 
Dose 
Route 
Schedule 
Cycle 
Length 
Hu5F9-G4 
(Magrolimab) 
650-1,000 mg 
acetaminophen 
oral (PO) and 25 
mg 
diphenhydramine 
(PO or IV) or a 
comparable 
regimen at least 
15 minutes 
before the first 
two doses of 
Hu5F9-G4 
(magrolimab). 
1 mg/kg 
priming 
dose, 
then 
30mg 
/kg per 
schedule  
IV over 
2 hours* 
and 
given 
before 
mogamu
lizumab
** 
1 mg/kg priming 
dose, then 30 mg/kg 
weekly for cycles 1-
2, then Q2W starting 
from cycle 3 
28 days  
(4 weeks) 
 
 
 
Mogamulizumab 
No additional 
premedications 
1 mg/kg IV  
Weekly for cycle 1, 
then Q2W starting 
from cycle 2 
Q2W = Every 2 weeks, IV = Intravenous 
*Priming dose will be given over 3 hours (+/- 30 minutes) 
**Hu5F9-G4 (magrolimab) to be administered before mogamulizumab on days when both 
treatments are given 
*** Within 24 hours prior to each of the first 2 doses of Hu5F9-G4infusion, patients must have a 
documented hemoglobin level of ≥9 g/dL.  Patients who do not meet these criteria must be transfused 
and have their hemoglobin rechecked to meet the minimum hemoglobin threshold prior to 
administering each of the first 2 doses of Hu5F9-G4.  An additional hemoglobin must be checked 3 
to 6 hours after the initiation of the first and second doses of Hu5F9-G4. The patient should be 
transfused as clinically appropriate.  Investigators should consider additional hemoglobin monitoring 
during the first week of treatment in patients with symptoms of anemia or at increased risk for 
complications of anemia. 
 
Table 4: Regimen Description for Phase 2 (Mogamulizumab Only Arm) 
Regimen Description 
Agent 
Premedications; 
Precautions 
Dose 
Route 
Schedule 
Cycle 
Length 
Mogamulizumab 
650-1,000 mg 
acetaminophen 
oral (PO) and 25 
mg 
diphenhydramine 
1 mg/kg 
IV  
Weekly for cycle 1, 
then Q2W starting 
from cycle 2 
28 days 
(4 weeks) 

 
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(PO or IV) or a 
comparable 
regimen at least 15 
minutes before the 
first dose of 
mogamulizumab. 
Q2W = Every 2 weeks, IV = Intravenous 
 
For patients who crossover to the Hu5F9-G4 (magrolimab)/mogamulizumab combination due to 
progression or lack of response after 6 months, no washout will be required and treatment will 
proceed with an identical schedule as the combination arm starting with the priming dose of 
Hu5F9-G4 (magrolimab). 
 
 
6.1.1 CTEP IND Agent 
 
6.1.1.1 Hu5F9-G4 (magrolimab) 
 
All cohorts in both phase 1B and phase 2 portion will follow the same dosing schedule, though 
the dose of Hu5F9-G4 (magrolimab) may vary, following the de-escalation design of the phase 
1B portion (see Table 2).  For patients receiving the combination of Hu5F9-G4 (magrolimab) 
and mogamulizumab, treatment will start with a priming dose of Hu5F9-G4 (magrolimab) of 
1mg/kg IV without mogamulizumab.  Starting one week later, patients will receive the 
designated dose of Hu5F9-G4 (magrolimab) (either 30mg/kg or 20mg/kg IV) every week for 
eight weeks.  After the first 8 weeks, the schedule of Hu5F9-G4 will change to every 2 weeks 
ongoing.  Mogamulizumab treatment will also start one week after the priming dose of Hu5F9-
G4 (magrolimab) at the FDA-approved dose and schedule. 
 
6.1.2 Other Agent 
 
6.1.2.1 Mogamulizumab 
 
All cohorts in both phase 1B and phase 2 portion will follow the same dosing schedule.  For 
patients receiving the combination of Hu5F9-G4 (magrolimab) and mogamulizumab, treatment 
will start with a priming dose of Hu5F9-G4 (magrolimab) of 1mg/kg IV without 
mogamulizumab.  Mogamulizumab treatment will start one week after the priming dose of 
Hu5F9-G4 (magrolimab) at the FDA-approved dose and schedule of 1mg/kg IV every week for 
4 weeks.  After the first 4 weeks of weekly mogamulizumab, the mogamulizumab schedule will 
change to every 2 weeks ongoing. 
 
6.2 
Definition of Dose-Limiting Toxicity 
 
DLT Definition:  A DLT is defined as any Grade 3 or greater AE that is assessed as related to at 
least 1 study treatment that occurs during the DLT Assessment Period (DLT exceptions are 
defined below).  The DLT period during the phase 1 study will be 4 weeks from the first infusion 
of Hu5F9-G4 (magrolimab) (priming infusion).  To be assessable for a DLT, patients must have 

 
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received at least three infusions of Hu5F9-G4 (magrolimab), two infusions of mogamulizumab, 
and completed four weeks of assessment, or else have experienced a DLT anytime after 
receiving the priming dose of Hu5F9-G4 (magrolimab).  Patients unable to receive the planned 
treatment during the four weeks due to treatment-related adverse events will also be considered 
to have experienced a DLT. 
 
DLT Exceptions:  The following are exceptions to the DLT definition and will NOT be 
considered a DLT: 
 
• 
Grade 3 anemia; however, Grade 3 hemolytic anemia is considered a DLT. 
• 
Grade 3 hyperbilirubinemia that resolves to ≤Grade 2 with supportive care within 1 week 
and is not associated with other clinically significant consequences.  
• 
Transient Grade 3 nausea, vomiting, diarrhea, local reactions, influenza-like symptoms, 
myalgias, fever, headache, acute pain, or skin toxicity that resolves to ≤Grade 2 within ≤72 
hours after medical management (e.g., supportive care, including immunosuppressant 
treatment) has been initiated. 
• 
Grade 3 fatigue that resolves to ≤Grade 2 within 1 week on study. 
• 
Grade 3 magrolimab-related infusion reactions in the absence of an optimal pretreatment 
regimen, which is defined as acetaminophen or a comparable non-steroidal anti-
inflammatory agent, plus an antihistamine and corticosteroids. 
• 
Grade 3 electrolyte disturbances (hyperkalemia, hypophosphatemia, hyperuricemia, etc.) 
that resolves to ≤Grade 2 or baseline within 1 week. 
• 
Grade 3 or 4 lymphopenia or grade 3 leukopenia not associated with other clinically 
significant consequences. 
• 
Transient (≤48 hours) Grade 3 fatigue, local reactions, flu-like symptoms, fever, headache, 
nausea, emesis, and diarrhea. 
• 
Other single laboratory values out of normal range that have no clinical correlate, and 
resolve to Grade ≤1 or to baseline within 7 days with adequate medical management. 
• 
Tumor flare phenomenon defined as local pain, irritation, or rash localized at sites of known 
or suspected tumor. 
• 
Grade 3 rash, erythroderma, skin pain or photosensitivity that resolves to ≤Grade 2 within 1 
week with adequate medical management.  Grade 4 rash or any grade Stevens-Johnson 
syndrome or toxic epidermal necrolysis will be considered DLTs. 
 
Management and dose modifications associated with the above adverse events are outlined in 
Section 7. 
 
Dose de-escalation will proceed within each cohort according to the following scheme (Figure 7) 
(Hong et al., 2019).  Dose-limiting toxicity (DLT) is defined above.   
 

 
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Figure 7: Phase 1b Dose De-escalation Design 
 
Six patients will be enrolled at dose level 1 of 30mg/kg Hu5F9-G4 (magrolimab) and 1mg/kg 
mogamulizumab.  If ≤ 1 DLT is observed in the initial 6 patients, then dose level 1 will be 
selected as the RP2D.  If 2 DLTs are observed in the initial 6 patients, then an additional group 
of 3 patients will be enrolled at dose level 1.  If there are no DLTs in this 3 patient group, then 
dose level 1 will be selected as the RP2D.  If at any point there are >2 DLTs seen at dose level 1, 
then this dose level will close, and 6 patients will be enrolled at the new dose level -1: 20mg/kg 
Hu5F9-G4 (magrolimab) and 1mg/kg mogamulizumab.  If ≤ 1 DLT is observed in the initial 6 
patients, then dose level -1 will be selected as the RP2D.  If 2 DLTs are observed in the initial 6 
patients, then an additional group of 3 patients will be enrolled at dose level -1.  If at any point 
there are >2 DLTs seen at dose level -1, then the trial will be stopped for unacceptable toxicity.  
It is believed that further reductions below a dose of 20mg/kg would not achieve adequate target 
occupancy for Hu5F9-G4 (magrolimab). 
 
6.3 
General Concomitant Medication and Supportive Care Guidelines 
 
Because there is a potential for interaction of Hu5F9-G4 (magrolimab) and mogamulizumab 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.  Corticosteroids may interfere with accurate disease response 
assessment.  High potency topical corticosteroids and systemic corticosteroids doses greater than 
10mg prednisone daily or its equivalent are prohibited unless needed to treat adverse events. 
Effort should be made to taper steroids to the minimum required dose. Other anti-lymphoma 
therapies are prohibited including retinoic acids and phototherapy. Appendix C (Patient Clinical 
Trial Wallet Card) should be provided to patients if available. 
 

 
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6.4 
Duration of Therapy 
 
In the absence of treatment delays due to adverse event(s), treatment may continue for 12 cycles 
or until one of the following criteria applies: 
 
• 
Disease progression.  Patients randomized to the mogamulizumab-only arm may 
crossover as per section 6.6.  Relapse in skin or blood compartments as defined by the 
response criteria is not considered progression and does not require removal from the 
treatment protocol. 
 
• 
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 
 
• 
Clinical progression 
 
• 
Patient non-compliance 
 
• 
Pregnancy 
 
o All women of child bearing 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 
 
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). 
 
6.5 
Duration of Follow-Up 
 
Patients will be followed for two years after their last treatment, until progression, or until the 
start of the next significant treatment, whichever occurs first.  Patients removed from study for 
unacceptable adverse event(s) will be followed until resolution or stabilization of the adverse 
event. 
 

 
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6.6 
Cross-over 
 
6.6.1 Eligibility for cross-over:  
 
Subjects randomized to the mogamulizumab-only arm will be eligible to cross-over to the 
combination arm of Hu5F9-G4 (magrolimab) and mogamulizumab if they meet EITHER of the 
following criteria: 
1. Have received at least 2 full treatment cycles of mogamulizumab and meet global 
criteria for progression of disease 
 
2. Have received at least 6 full treatment cycles of mogamulizumab and meet global 
criteria for stable disease 
 
Additionally, to be eligible for cross-over, subjects must meet BOTH of the following criteria: 
1.  Meet the eligibility criteria at the time of cross-over.  The only exception to the 
eligibility criteria will be that subjects who have active large cell transformation 
(LCT) at the time of cross-over will be eligible for cross-over.  
 
2. Subjects must also have a skin biopsy performed within 4 weeks prior to cross-
over with a pathologic diagnosis confirming cutaneous lymphoma.  It is strongly 
recommended to perform molecular studies of TCR clonality if there is ambiguity 
in the diagnosis.  This criteria is to exclude the possibility of progression 
incorrectly being attributed to a mogamulizumab-associated rash.  
 
Subjects will have 4 weeks from the date of progression to meet eligibility for cross-over.  
 
6.6.2 Procedures related to cross-over: 
Subjects who cross-over to the combination therapy arm will adhere to the study calendar.  The 
following procedures do not need to be repeated at baseline if performed within 4 weeks of 
cross-over: 
• Imaging 
• Flow cytometry 
• Skin biopsies 
• Correlative blood collection 
 
7. DOSING DELAYS/DOSE MODIFICATIONS 
 
Dose Level 
Hu5F9-G4 (Magrolimab) 
Maintenance Dose 
Mogamulizumab 
-1 
1 mg/kg IV priming dose; Then 20 
mg/kg IV weekly in Cycles 1 & 2 
followed by Q2W in ≥ Cycle 3.  
Give before mogamulizumab. 
Weekly for cycle 1, then 
Q2W starting from cycle 2 
1 
1 mg/kg IV priming dose; Then 30 
mg/kg IV weekly in Cycles 1 & 2 
Weekly for cycle 1, then 
Q2W starting from cycle 2 

 
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followed by Q2W in ≥ Cycle 3.  
Give before mogamulizumab. 
 
Dose reductions are not required for Hu5F9-G4 (magrolimab), except in case of anemia.  For all 
other treatment-related adverse events, Hu5F9-G4 (magrolimab) can be reduced by 1 dose level 
if a Grade 3 or higher AE that is related to Hu5F9-G4 (magrolimab) is observed and does not 
resolve within 2 weeks. 
 
The following modifications should be performed for treatment-related adverse events.  
 
Nausea 
Management/Next Dose for  
Hu5F9-G4 (magrolimab) and Mogamulizumab 
≤ Grade 1 
No change in dose 
Grade 2 
Hold until ≤ Grade 1.  Resume at same dose level. 
Grade 3 
Hold* until <  Grade 2.  Resume at one dose level lower, if indicated. 
Grade 4 
Off protocol therapy 
*Patients requiring a delay of >2 weeks should go off protocol therapy. 
 
Recommended management:  antiemetics. 
 
 
Vomiting 
Management/Next Dose for Hu5F9-G4 (magrolimab) and 
Mogamulizumab 
≤ Grade 1 
No change in dose 
Grade 2 
Hold until ≤ Grade 1.  Resume at same dose level. 
Grade 3 
Hold* until < Grade 2.  Resume at one dose level lower, if indicated. 
Grade 4 
Off protocol therapy 
*Patients requiring a delay of >2 weeks should go off protocol therapy. 
 
Recommended management:  antiemetics. 
 
 
Diarrhea 
Management/Next Dose for Hu5F9-G4 (magrolimab) and 
Mogamulizumab 
≤ Grade 1 
No change in dose 
Grade 2 
Hold until ≤ Grade 1.  Resume at same dose level. 
Grade 3 
Hold* until < Grade 2.  Resume at one dose level lower, if indicated. 
Grade 4 
Off protocol therapy 
*Patients requiring a delay of >2 weeks should go off protocol therapy. 
 
Recommended management:  Loperamide antidiarrheal therapy 
Dosage schedule:  4 mg at first onset, followed by 2 mg with each loose motion until diarrhea-
free for 12 hours (maximum dosage:  16 mg/24 hours) 
Adjunct anti-diarrheal therapy is permitted and should be recorded when used. 
 

 
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Neutropenia 
Management/Next Dose for Hu5F9-G4 (magrolimab) and 
Mogamulizumab 
≤ Grade 1 
No change in dose 
Grade 2 
Hold until ≤ Grade 1.  Resume at same dose level. 
Grade 3 
Hold* until < Grade 2.  Resume at one dose level lower, if indicated. 
Grade 4 
Off protocol therapy 
*Patients requiring a delay of >2 weeks should go off protocol therapy. 
 
Recommended management: Growth factor 
 
 
Thrombocytopenia 
Management/Next Dose for Hu5F9-G4 (magrolimab) and 
Mogamulizumab 
≤ Grade 1 
No change in dose 
Grade 2 
Hold until ≤ Grade 1.  Resume at same dose level. 
Grade 3 
Hold* until < Grade 2.  Resume at one dose level lower, if indicated. 
Grade 4 
Off protocol therapy 
*Patients requiring a delay of >2 weeks should go off protocol therapy. 
 
 
 
Anemia 
Management/Next Dose for 
Hu5F9-G4 (magrolimab) 
Management/Next Dose for 
Mogamulizumab 
≤ Grade 1 
No change in dose 
No change in dose 
≤ Grade 2 
No change in dose 
No change in dose 
Grade 3 hemolytic 
anemia that is 
medically significant 
(requiring 
hospitalization or 
prolongation of 
existing 
hospitalization, 
disabling, or limiting 
self-care ADLs) 
 
First occurrence: Reduce by 1 dose 
level.  
• If recurs after 1 dose level 
reduction: permanently 
discontinue unless patient is 
clinically benefitting. 
• Second occurrence: 
permanently discontinue 
Hold* until ≤ Grade 2.  Resume at 
same dose level. 
 
Grade 4 
First occurrence: permanently 
discontinue unless patient is 
clinically benefitting.** 
First occurrence: permanently 
discontinue unless patient is 
clinically benefitting.** 
 *Patients requiring a delay of >2 weeks should go off protocol therapy. 
**If Grade 4 anemia is unrelated to underlying disease, permanently discontinue Hu5F9-G4 
(magrolimab) regardless of clinical benefit.  Mogamulizumab may be resumed if anemia is 
resolved to Grade ≤ 2 and if there may be a clinical benefit from the treatment. 
Recommended management:  Transfusions as per section 7.1 

 
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Rash* 
(including 
maculopapular, 
pruritus, 
erythroderma, 
photosensitivity, and 
skin pain) 
Management/Next Dose for 
Hu5F9-G4 (magrolimab) 
Management/Next Dose for 
Mogamulizumab 
 
Grade 2 
Magrolimab** should be continued 
without dose modification. 
Mogamulizumab*** may be held at 
investigator’s discretion.   
Grade 3 
Magrolimab** may be held at the 
investigator’s discretion.  
 
Mogamulizumab*** may be held at 
investigator’s discretion.   
Grade 4 
Off protocol therapy 
Off protocol therapy 
*It is recommended to perform skin biopsies when possible with molecular T-cell receptor 
clonality studies to help distinguish rash from progressive disease 
** Magrolimab may be held at the investigator’s discretion for up to 2 weeks from the time of 
the scheduled infusion for grade 3 rash.  Patients requiring a magrolimab delay of >2 weeks 
from their scheduled infusion should go off protocol therapy. Upon restarting magrolimab after 
a delay, there will be no dose reduction. 
*** Mogamulizumab may be held up to 4 weeks from the time of the scheduled infusion for 
grade 2-3 rash. Patients requiring a mogamulizumab delay of >4 weeks from their scheduled 
infusion should go off protocol therapy.  Upon restarting mogamulizumab after a delay, there 
will be no dose reduction. 
 
Recommended management:  High potency topical steroids may be used for grade 2-3.  
Subjects should apply topical steroids only to areas of suspected rash and avoid areas of known 
lymphoma disease and should try to reduce topical steroids to medium or low potency as 
tolerated.   For grade 2, systemic corticosteroids may be given.  For grade 3, systemic 
corticosteroids should be given. A dose of 40mg prednisone daily or equivalent is suggested.  If 
systemic corticosteroids are given, efforts should be made to taper as tolerated to a dose of 
10mg prednisone daily or equivalent. 
 
 
All Other Drug-
related Toxicity*** 
Management/Next Dose for Hu5F9-G4 (magrolimab) and 
Mogamulizumab 
Grade 3 
Hold** until ≤ Grade 2.   
Grade 4 
Off protocol therapy 
* Patients with intolerable or persistent Grade 2 drug-related AE may hold study medications 
for up to 2 weeks at physician discretion. 
**Patients requiring a delay of >2 weeks should go off protocol therapy.  
*** Lymphopenia and/or leukopenia are the pharmacologic effect of mogamulizumab and will 
not be considered an AE for this study.  However, neutropenia will be considered an AE and 
managed as above. 

 
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All Other Drug-
related Toxicity*** 
Management/Next Dose for Hu5F9-G4 (magrolimab) and 
Mogamulizumab 
 
 
Dosing interruptions are permitted in the case of medical/surgical events or logistical reasons not 
related to study therapy (e.g., elective surgery, unrelated medical events, patient vacation, and/or 
holidays). Patients should be placed back on study therapy within 2 weeks of the interruption.   
The reason for interruption should be documented in the patient’s study record.  
 
7.1 
Safety Management Guidelines  
 
7.1.1 Management of Infusion-related Reactions 
 
The most common adverse events associated with IRRs include chills, pyrexia, back pain, 
nausea, vomiting, hypotension, dyspnea, and headache.  These primarily occur with the first two 
doses of Hu5F9-G4 (magrolimab) (1 mg/kg), and are mostly observed during the infusion or 
several hours afterward.  
 
Preventive Measures 
 
Premedication should include oral acetaminophen and an antihistamine (IV or oral) before the 
initial doses of Hu5F9-G4 (magrolimab) or in the case of re-priming of Hu5F9-G4 
(magrolimab).  Premedication is required prior to the administration of the intial doses of 
Hu5F9-G4 (magrolimab).  Refer to Section 6.1 Agent Administration.   
 
Management of IRRs 
 
• For grade 1 IRRs, described as mild transient reaction, infusion interruption is not indicated, 
intervention is not indicated: 
• Remain at bedside and monitor patient until recovery from symptoms. 
• For grade 2 IRRs, infusion interruption is indicated, but patient responds promptly to 
symptomatic treatment (e.g., antihistamines, non-steroidal anti-inflammatory drugs, 
narcotics, corticosteroids, IV fluids); and prophylactic medications are indicated for 
≤24 hours: 
• Stop the Hu5F9-G4 (magrolimab) infusion, begin an intravenous (IV) infusion of 
normal saline, and consider treating the patient with diphenhydramine 50 mg IV (or 
equivalent) and/or 500–750 mg oral acetaminophen. 
• Remain at bedside and monitor patient until resolution of symptoms. 
• Corticosteroid therapy may also be given at the discretion of the Investigator. 
• If the infusion is interrupted, wait until symptoms resolve, then restart the infusion at 
50% of the original infusion rate. 
• If no further complications occur after 1 hour (± 10 minutes), the rate may be 
increased to 100% of the original infusion rate.  Monitor the patient closely. 
• If symptoms recur, stop infusion and disconnect patient from the infusion apparatus.  
No further Hu5F9-G4 (magrolimab) will be administered at that visit. 

 
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• Premedications should be considered before any future infusions. 
• The amount of Hu5F9-G4 (magrolimab) infused must be recorded on the case report 
form (eCRF). 
• Patients who experience a grade 2 IRR during the post-infusion observation period 
that does not resolve during that time should be observed until the AE resolves, with 
vital sign measurements as medically indicated for the management of the AE. 
• For grade 3 or grade 4 IRR, where grade 3 is described as prolonged infusion-related 
reactions (e.g., not rapidly responsive to symptomatic medication and/or brief interruption of 
infusion), or recurrence of symptoms following initial improvement, or where hospitalization 
is indicated for other clinical sequelae (e.g., renal impairment, pulmonary infiltrates). 
grade 4 is described as having life-threatening consequences and where urgent intervention 
indicated. 
• Immediately discontinue infusion of Hu5F9-G4 (magrolimab). 
• Begin an IV infusion of normal saline, and consider treating the patient as follows: 
Administer bronchodilators, epinephrine 0.2 to 1 mg of a 1:1,000 solution for 
subcutaneous administration or 0.1 to 0.25 mg of a 1:10,000 solution injected slowly 
for IV administration and/or diphenhydramine 50 mg IV with methylprednisolone 
100 mg IV (or equivalent), as needed. 
• The patient should be monitored until the Investigator is comfortable that the 
symptoms will not recur. 
• Patients who have grade 4 IRRs occurring with the first dose (priming dose) will be 
permanently discontinued from study treatment. 
• Patients who experience grade 3 IRRs must be given premedication prior to all 
subsequent doses.  In this setting, premedication with oral acetaminophen (650 mg), 
oral or IV diphenhydramine (25–50 mg), and IV dexamethasone (4–20 mg), or a 
comparable regimen, is recommended for the subsequent 2 doses.  Continued 
premedication with corticosteroids beyond these 2 doses may be administered at the 
discretion of the treating physician. 
• Patients who receive premedication with a corticosteroid and still experience a grade 
3 or 4 infusion-related reaction will be permanently discontinued from study 
treatment. 
• Investigators should follow their institutional guidelines for the treatment of 
anaphylaxis. 
• All patients with grade 3 or greater IRRs will be observed until the AE(s) resolves or 
stabilizes, with vital sign measurements and additional evaluations, as medically 
indicated for the management of the AE(s). 
 
In the case of late-occurring hypersensitivity symptoms (e.g., appearance of localized or 
eneralized pruritus after Day 1 but within 1 week after treatment), symptomatic treatment may be 
given (e.g., oral antihistamine or corticosteroids). 
 
A premedication regimen (oral acetaminophen and diphenhydramine, or comparable regimen) is 
required before the initial doses of Hu5F9-G4 (magrolimab) and in case of repriming of the 
participant after >4 weeks interruption in Hu5F9-G4 (magrolimab) treatment. 
 

 
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7.1.2 Tumor Lysis Syndrome 
 
In the case of evidence for tumor lysis syndrome associated with Hu5F9-G4 (magrolimab), 
patients will be admitted to the hospital as clinically indicated.  Standard management will 
include vigorous IV hydration; correction of acidosis, if present; hypouricemic agents; and close 
monitoring of serum uric acid, phosphorus, and electrolytes.  Study treatment should be held 
until the patient’s condition resolves or stabilizes. 
 
7.1.3 Hemagglutination and Microangiopathy 
 
In the phase 1 trial experience with Hu5F9-G4 (magrolimab) in solid tumors and AML, 
agglutination of RBCs has been observed on peripheral smear.  Hu5F9-G4-related 
microangiopathy is a possible sequela of hemagglutination; however, it has not been observed in 
the ongoing phase 1 clinical trials to date.  In addition, AEs may be associated with findings of 
hemagglutination.  Monitoring of hemagglutination and microangiopathy includes physical exam 
assessments, complete blood counts (CBCs), peripheral smears, serum chemistries, and D-dimer 
testing as outlined in the schedule of assessments (SOA).  Peripheral smears will be read by local 
sites with reporting of RBC agglutination, spherocytosis, and evidence of RBC destruction 
(e.g., schistocytosis, fragments) when present.  The presence or absence of hemagglutination 
and/or microangiopathy on peripheral smear will be incorporated into the AE severity grading 
for hemagglutination and microangiopathy, as described below.  The degree of peripheral smear 
findings will be quantified according to the appropriate scale (Appendix H) for sites that have the 
capability to do so, but is not required.  Peripheral smear slides will be retained by the Sponsor 
and stored for future analyses.  AEs relating to hemaggplutination and microangiopathy will be 
graded for toxicity according to the scale below. 
AE Severity Grading for Hemagglutination and Microangiopathy 
Grade 1: 
Evidence of hemagglutination and/or microangiopathy on peripheral blood smear 
AND associated clinical sequelae that is asymptomatic or mild, not requiring 
intervention  
Grade 2: 
Evidence of hemagglutination and/or microangiopathy on peripheral blood smear 
AND associated clinical sequelae that requires medical intervention 
Grade 3: 
Evidence of hemagglutination and/or microangiopathy on peripheral blood smear 
AND associated clinical sequelae that is medically significant, requiring 
hospitalization or prolongation of existing hospitalization, disabling, or limiting 
self-care activities of daily living (ADLs)  
Grade 4: 
Evidence of hemagglutination and/or microangiopathy on peripheral blood smear 
AND associated clinical sequelae that is life threatening or requires urgent 
intervention 
Grade 5: 
Evidence of hemagglutination and/or microangiopathy on peripheral blood smear 
AND associated clinical sequelae that results in death 
 
7.1.4 Anemia, Blood Cross-Matching, and Red Blood Cell Transfusion Procedures 
 

 
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Patients must have a documented hemoglobin ≥9 g/dL within 24 hours prior to receiving the first 
and second dose of Hu5F9-G4 (magrolimab).  Patients who do not meet these criteria must be 
transfused and have their hemoglobin rechecked to meet the minimum hemoglobin threshold 
prior to administering the first two doses of magrolimab.  An additional hemoglobin 
measurement must be performed 3 to 6 hours after the initiation of the first and second doses of 
Hu5F9-G4 (magrolimab).  The patient should be transfused as clinically appropriate.  
Investigators should consider additional hemoglobin monitoring during the first week of 
treatment in patients with symptoms of anemia or at increased risk for complications of anemia.  
 
Patients with a low baseline hemogloblin level, especially those with cardiac history or risk 
factors, must be monitored closely after initial administrations of Hu5F9-G4 (magrolimab) as 
preexisting anemia can be exacerbated. 
 
Hu5F9-G4 (magrolimab) binds to red cells and leads to erythrophagocytosis.  This, coupled with 
anemia from other causes in patients with cancers, means that care has to be taken with RBC 
cross-matching and packed red blood cell (PRBC) transfusions.  There is a possibility that 
treatment with Hu5F9-G4 (magrolimab) may obscure assessment of RBC phenotyping. 
During the Screening Period prior to initiation of Hu5F9-G4 (magrolimab) therapy, blood cell 
ABO phenotyping for minor antigens, type and screen (ABO/Rh), and Direct Antiglobulin Test 
(DAT) will be performed for each patient.  This, together with using the prior phenotype, will 
facilitate allocation of properly cross-matched blood, should a blood transfusion be warranted. 
Procedure for patients after exposure to Hu5F9-G4 (magrolimab): 
1. ABO, Rh, and DAT may be pan-reactive due to Hu5F9-G4 (magrolimab) binding to red 
cells.  Therefore, if a non-urgent transfusion is ordered by the Investigator, perform the 
following procedures:  
• Front Type:  ethylenediaminetetraacetic acid (EDTA)/glycine-acid (EGA) Treat 
cells ×2 (maximum) and Warm Wash ×4 (minimum) with 0.9% Saline. 
• Back Type:  Perform reverse anti-human globulin for both A and B. 
• If a valid ABO type cannot be obtained, mark the final report as invalid and notify 
the transfusion service for the site. 
2. Antibody screen 
If a pan-agglutinin/warm autoantibody is present in low ionic strength solution (LISS), repeat 
the antibody screen with polyethylene glycol (PeG).  Perform PeG adsorption studies and 
elution studies. 
3. Notify blood transfusion centers/blood banks of this interference with blood bank testing and 
inform them that a patient will receive Hu5F9-G4 (magrolimab). 
4. For all elective RBC and platelet transfusions, use leukocyte-reduced and gamma-irradiated 
units per institutional guidelines. 
5. For RBC transfusions, phenotype/genotype matched units are preferred. 
6. In case ABO/Rh type cannot be resolved, use pretreatment (historical) phenotype/genotype 
matched units for minor RBC antigens (CcDEe and Kk, to the feasible extent).  Regarding 
the ABO type, historical blood group or O type can be used as per the institutional 
guidelines. 

 
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7. For emergency transfusions, the transfusion centers may consider using emergency Group O 
red cells if phenotype/genotype matched units are not available. 
8. Cross-match interference by RBCs due to treatment with Hu5F9-G4 (magrolimab) may be 
resolved by use of gamma-clone anti-IgG and multiple alloadsorptions with papain-treated 
RBC samples, pooled single donor apheresis platelets or commercial human platelet 
concentrate product if required 
 
7.1.5 Blood Components for Transfusion 
 
For all elective red cell transfusions, leukocyte-reduced units matched for the phenotype of the 
patients (as described above) will be used.  Where exact matching for all the specified blood 
groups proves impractical (e.g., for any of the blood groups M, N, and S compromising the MNS 
system [MNS]), local sites will decide on the best matched donor units to be used.  
Cytomegalovirus (CMV) matching (i.e., CMV seronegative units for CMV-seronegative 
patients) will not be required for this study because it will limit the inventory for antigen 
matching. 
 
If the cross-match is incompatible, the RBC units that are Coomb's crossmatch-incompatible will 
be selected (e.g., phenotype-matched or least incompatible) for issue at the discretion of the local 
site’s Transfusion Service Medical Director or equivalent person, where available.  Such 
instances will be documented, along with consent signatures obtained from ordering physicians, 
according to best practices in blood bank policies and procedures. 
For emergency transfusions, the transfusion laboratory may consider using emergency Group O 
Rhesus negative units if phenotyped units are not available. 
Blood plasma therapy will be blood-type specific.  Platelets will be blood type compatible 
whenever possible, and if not, will have been tested and found not to have high titer anti-A or 
anti-B. 
7.1.6 Thromboembolic Events 
 
Thromboembolic events including deep vein thromboses and pulmonary embolisms, have been 
reported in some patients receiving Hu5F9-G4 (magrolimab), sometimes early in therapy. 
 
• No clear or consistent relationship between clinical and thromboembolic events and 
Hu5F9-G4 (magrolimab) use has been observed. 
• Close monitoring for symptoms of thromboembolic events is required. 
• Patients should be treated as per standard of care. 
 
7.1.7 Pneumonitis 
 
Pneumonitis has been infrequently observed in patients receiving Hu5F9-G4 (magrolimab).  It is 
currently unknown if Hu5F9-G4 (magrolimab)increases the risk of pneumonitis. 
 
In instances of suspected pneumonitis: 
• First, rule out non-inflammatory causes (e.g., infections). 

 
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• If non-inflammatory cause identified, treat accordingly and continue therapy per protocol. 
• Evaluate with imaging (e.g., chest x-ray or computed tomography) and pulmonary 
consultation. 
• Management of potential pneumonitis and follow-up management of Immune-Related 
Adverse Events Treated with Immune Checkpoint Inhibitor Therapy: American Society 
of Clinical Oncology Clinical Practice Guideline should be followed. 
 
Pneumonitis Management Algorithm 
CTCAE Grade of 
Pneumonitis 
Management 
Follow-Up 
Grade 1 
Radiographic changes (CXR 
or CT) only. 
Monitor for signs and symptoms weekly and 
consider monitoring with CXR. 
Consider pulmonary and infectious disease 
consults. 
Consider re-imaging with CT in 
3-4 weeks as clinically indicated. 
May resume magrolimab with 
radiographic evidence of 
improvement or resolution. 
If no clinical improvement or 
worsening, treat as Grade 2. 
Grade 2 
Mild to moderate new 
symptoms. 
Interrupt magrolimab therapy per protocol. 
Pulmonary and infectious disease consults. 
Consider empirical antibiotics. 
Monitor signs and symptoms every 2-3 days; 
consider hospitalization. 
1 mg/kg/day oral prednisone or IV equivalent. 
Consider bronchoscopy, lung biopsy. 
Re-image every 1-3 days. 
If improving to baseline, taper 
corticosteroids over 4-6 weeks and 
resume magrolimab therapy per 
protocol. 
If no clinical improvement after 
48-72 h or worsening, treatas 
Grade 3-4. 
Grade 3-4 
Severe new symptoms; 
new/worsening hypoxia; 
life-threatening. 
Discontinue magrolimab therapy.Hospitalize. 
Pulmonary and infectious disease consults. 
1-2 mg/kg/day methylprednisolone IV or IV 
equivalent. 
Add empirical antibiotics and consider 
prophylactic antibiotics for opportunistic 
infections. 
Consider bronchoscopy, lung biopsy. 
If improving to baseline, taper 
corticosteroids over 4-6 weeks. If 
no clinical improvement after 48 h 
or worsening, consider additional 
immunosuppression 
(eg, infliximab, cyclophosphamide, 
IV immunoglobulin, 
mycophenolatemofetil). 
CT = computed tomography; CTCAE = Common Terminology Criteria for Adverse Events; CXR = chest 
x-ray; IV = intravenous 
 
 
8. PHARMACEUTICAL INFORMATION 
 
A list of the adverse events and potential risks associated with the investigational or commercial 
agents administered in this study can be found in Section 10.1. 
 
8.1 
CTEP IND Agent 
 
8.1.1 Hu5F9-G4 (magrolimab) (NSC 809249)  
 

 
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Classification: A monoclonal antibody CD47 inhibitor 
 
CAS Registry Number: 1682749-68-3 
 
Molecular Formula: C6462H9960N1718O2027S48 
            M.W.: 
145687.6 
Daltons 
(predicted) 
 
Mode of Action:  Phagocytosis of tumor cells is blocked when CD47, a cell surface glycoprotein 
widely expressed by cancer cells, binds to the receptor, SIRPα, found on innate immune system cells 
like macrophages and dendritic cells.  Hu5F9-G4 blocks the binding of this “don’t eat me” signal 
which then allows the activation of macrophages to phagocytose cancer cells through the induction 
of pro-phagocytic signaling. Nonclinical studies show that CD47 inhibition combined with other 
anti-tumor antibodies like rituximab or cetuximab has the potential to provide synergistic pro-
phagocytic signaling to macrophages.  
 
Description: Hu5F9-G4(magrolimab) is a recombinant humanized IgG4 monoclonal antibody of 
the IgG4 kappa isotype containing a Ser-Pro substitution in the hinge region of the heavy chain. It 
comprises a disulfide linked glycosylated tetramer, consisting of 2 identical 444 amino acid heavy 
gamma chains and 2 identical 219 amino acid kappa light chains.  
 
How Supplied: Gilead Sciences supplies and CTEP, DCTD, NCI distributes Hu5F9-G4 
(magrolimab) injection as 200 mg/10 mL (20 mg/mL) single-use vials in a type I borosilicate glass 
vial with coated elastomeric stopper and aluminum crimp over seals with a flip-off cap.  Hu5F9-
G4(magrolimab) is a sterile, clear to slightly opalescent, colorless to slightly yellow, preservative-
free liquid in 10 mL vials. The product is formulated in 0.01% (weight/volume [w/v]) polysorbate 
20, 5% (w/v) sorbitol, 10 mM sodium acetate / acetic acid, pH 5.0, and sterile water for injection.  
 
Preparation: Use pre-filled 250 mL and 500 mL normal saline bag (preferred) but an empty IV bag 
is also acceptable.   
 
Magrolimab is compatible in IV bags  and peripheral/central IV line made of the following materials: 
Polyvinyl chloride (PVC) with or without DEHP; Polyolefin (PO), Polyethylene (PE) and 
Polypropylene (PP); Ethyl vinyl acetate (EVA), Polyether sulfone (PES) in-line filters; Polyurethane 
(PU); Fluorinated ethylene propylene (FEP); Thermoplastic elastomer (TPE); Stainless steel; 
Silicone; Polycarbonate (PC); Acrylonitrile butadiene styrene (ABS); Polytetrafluoroethylene 
(PTFE); 
Low 
density 
polyethylene 
(LDPE); 
Polyimide; 
Delrin; 
Acrylate 
polymer; 
Polyoxymethylene; Polyamide ; Titanium; Methyl methacrylate acrylonitrile butadiene styrene 
(MABS); Acrylic copolymer and nylon; Polyvinylchloride (PVC) with Tris (2-ethylhexyl) 
Trimellitate (TOTM); Polyester or copolyester ; Polyvinylidene fluoride ; Ethyl acrylate-styrene-
methyl methacrylate copolymer; Isoprene rubber or polyisoprene; Fluorosilicone; and Polyethylene 
terephthalate  
 
The following proprietary closed system transfer devices (CSTDs) are compatible with magrolimab:  
PhaSeal, PhaSeal Optima, Equashield, ChemolockT, SmartSite with Texium and Spiros.  
 
Magrolimab IV solution can be prepared from multiple lots but using one lot per dose is preferred. 

 
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▪ For doses of 1 mg/kg or less, dilute dose in 250 mL 0.9% sodium chloride  
▪ For doses greater than 1 mg/kg, dilute dose in 500 mL 0.9% sodium chloride   
 
- Obtain the required number of vials and examine them for discoloration, cloudiness, or 
particles. Do not use if particulate matter or discoloration is noted. 
- If using a pre-filled 250 mL or 500 mL 0.9% sodium chloride bag, remove normal saline 
volume equivalent to the calculated dose volume of magrolimab from the pre-filled saline 
bag. Then, add the calculated dose volume of magrolimab into the pre-filled saline IV bag. 
- If using an empty IV bag, add the calculated volume of 0.9% sodium chloride into the 
empty IV bag followed by the calculated dose volume of magrolimab to make a total volume 
of 250 mL or 500 mL.  
- Gently invert the IV bag 3-6 times to mix the solution. Avoid foaming IV solution. If 
particulate matter or discoloration occurs, do not use the IV preparation.  
 
The prepared IV solution can be stored as follows: 
▪ 250 C (770 F) up to 8 hours, which includes the preparation time and the completion time of 
the infusion. Discard if exceeding 8 hours.  
▪ 2°C - 8°C (36° F to 46° F) for up to 16 hours, which includes the preparation time and the 
completion time of the infusion including 1 hour for IV solution to equilibrate at room 
temperature before administration.  Discard IV if exceeding 16 hours.   
 
 
 
Storage:  Store vials at 2°C - 8°C (36° F to 46° F) in the original carton, protected from light.  Do not 
freeze. 
 
If a storage temperature excursion is identified, promptly return Hu5F9-G4 
(magrolimab) to 2°C -8°C (36° F to 46° F) 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 stability studies of the intact or unused vials are on-going. 
 
CAUTION:  The single-use injectable vial contains no antibacterial 
preservatives.  Therefore, it is advised that the reconstituted product be 
discarded 8 hours after initial entry.  
 
Route of Administration: Intravenous.  Do not administer as an IV bolus. 
 
Method of Administration: A priming dose of Hu5F9-G4 (magrolimab) is required 1 week prior to 
Cycle1 Day1. The priming dose (1 mg / kg) will be infused over 3 hours (+/- 30 minutes) via a 

 
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peripheral or central line through a polyethersulfone (PES) in-line IV filter set. Prime the IV line with 
the prepared IV solution before starting the infusion.  After completing the infusion, the IV line can 
be flushed with 40 mL normal saline at the same infusion rate in the table below or as per institutional 
guidelines.   Subsequent IV doses are to be infused over 2 hours (+/- 10 minutes). 
 
Dose 
Infusion 
volume (mL) 
Infusion time 
      Rate 
(mL/min) 
Rate 
(mL/Hour) 
1 mg/Kg 
250 
3 hours (+/- 30 mins) 
1.4 
83 
15 mg/Kg 
500 
3 hours (+/- 30 mins) 
2.8 
167 
30 mg/Kg 
500 
2 hours (+/- 30 mins) 
4.2 
250 
 
 
Oral acetaminophen 650 mg to 1000 mg and oral/IV diphenhydramine 25 to 50 mg or 
comparable regimen are acceptable premedication.  Premedication is required prior to the 
administration of the first 4 doses of magrolimab and in case of reintroduction with repriming. 
Premedication during subsequent infusions may be continued based on the treating investigator’s 
clinical judgment and the presence/severity of prior infusion-related reactions. In the case of a 
Grade 3 infusion-related reaction, a premedication regimen for subsequent infusions may be 
needed. Refer to the protocol for additional guidance. 
 
Patient Care Implications:  Advise men and women of reproductive potential to use effective 
contraception while receiving study treatment and for 4 months after the last dose of Hu-5F9 
(magrolimab). Male patients whose partners are pregnant may continue study treatment and should 
use barrier method contraception (condom) to prevent exposing the fetus. Refer to the protocol 
document for specific guidance. 
 
Since infusion reactions can occur, all patients should be monitored for 1-hour post-infusion for 
the priming dose. Patients who experience any treatment-related adverse events during the 
observation period should be further monitored as clinically appropriate (e.g., for up to 24 hours 
post-dose).  All patients should be monitored for 1-hour post-infusion for Cycle 1. Further doses 
(Cycle 2+) do not require post-infusion observation. Patients who experience any treatment-
related AEs during the observation period should be further monitored as clinically appropriate. 
Follow the protocol’s instructions for managing infusion symptoms and hypersensitivity to 
Hu5F9-G4 (magrolimab). 
 
Availability 
 
Hu5F9-G4 (magrolimab) is an investigational agent supplied to investigators by the Division of 
Cancer Treatment and Diagnosis (DCTD), NCI. 
 
Hu5F9-G4 (magrolimab) is provided to the NCI under a Collaborative Agreement between the 
Pharmaceutical Collaborator and the DCTD, NCI (see Section 13.5). 
 
8.1.2 Agent Ordering and Agent Accountability 
 
8.1.2.1 NCI-supplied agents may be requested by eligible participating Investigators (or their 

 
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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. 
 
Confirmation of study patient enrollment onto the study is required for initial drug 
shipment. 
 
Submit agent requests through the PMB Online Agent Order Processing (OAOP) 
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.   
 
8.1.2.2 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. 
 
8.1.3 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. 
 
8.1.4 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 

 
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• 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(s) 
 
8.2.1 Mogamulizumab (NSC 791064) 
Please refer to the Mogamulizumab Package Insert for complete information. 
 
Other Names: KW-0761, AMG 761, POTELIGEO® 
 
Classification: Anti-CC chemokine receptor 4 (CCR4) MAb 
 
Molecular Weight: ~149 kDa 
 
Mode of Action:  Mogamulizumab selectively binds to and blocks the activity of CC chemokine 
receptor 4 (CCR4), a G-coupled-protein receptor for C-C chemokines expressed on the surfaces 
of some types of T cells, endothelial cells, and neurons.  Mogamulizumab is a defucosylated, 
humanized, IgG1 MAb with lack of fucose resulting in enhanced antibody-dependent cellular 
cytotoxicity (ADATA COORDINATING CENTER) activity.  It may induce ADATA 
COORDINATING CENTER against CCR4-positive T cells and inhibit CCR4-mediated signal 
transduction pathways leading to chemokine-mediated cellular migration and proliferation of T 
cells, and chemokine-mediated angiogenesis. 
 
How Supplied:  Mogamulizumab (mogamulizumab-kpkc) injection is a sterile, preservative-free, 
clear to slightly opalescent colorless solution supplied in a carton containing one 20 mg/5 mL (4 
mg/mL), single dose glass vial (NDC 42747-761-01). 
Preparation:  Visually inspect drug product solution for particulate matter and discoloration prior to 
administration.  Mogamulizumab is a clear to slightly opalescent colorless solution.  Discard the 
vial if cloudiness, discoloration, or particulates are observed. 
• Calculate the dose (mg/kg) and number of vials of Mogamulizumab needed to prepare the 
infusion solution based on patient weight. 
• Aseptically withdraw the required volume of Mogamulizumab into the syringe and transfer 
into an intravenous (IV) bag containing 0.9% Sodium Chloride Injection, USP.  The final 
concentration of the diluted solution should be between 0.1 mg/mL to 3.0 mg/mL. 
• Mix diluted solution by gentle inversion.  Do not shake. 
• Discard any unused portion left in the vial. 
The diluted solution is compatible with polyvinyl chloride (PVC) or polyolefin (PO) infusion 
bags.  
 
Storage: Store vials under refrigeration at 2°C to 8°C (36°F to 46°F) in original package to protect 
from light until time of use.  Do not freeze.  Do not shake. 
 
Stability: After preparation, infuse the Mogamulizumab solution immediately, or store under 
refrigeration at 2°C to 8°C (36°F to 46°F) for no more than 4 hours from the time of infusion 
preparation.  Do not freeze.  Do not shake. 
Route of Administration: Intravenous (IV) infusion 

 
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78 
 
Method of Administration:  
• Administer infusion solution over at least 60 minutes through an intravenous line containing 
a sterile, low protein binding, 0.22 micron (or equivalent) in-line filter. 
• Do not mix Mogamulizumab with other drugs. 
• Do not co-administer other drugs through the same intravenous line. 
 
Patient Care Implications: Refer to the protocol for information on evaluation and management 
of infusion related reactions. 
 
Agent Ordering:  Commercially available from various manufacturers.  See package insert for 
further information. 
 
 
9. STATISTICAL CONSIDERATIONS 
 
9.1 
Study Design/Endpoints 
 
This is a combined phase 1b/2 multicenter, open label, interventional study to evaluate the safety 
(phase 1b) and efficacy (phase 2) of the combination of Hu5F9-G4 (magrolimab) with 
mogamulizumab.  The phase 1b portion will be a single arm, dose de-escalation 6+3 design to 
determine a RP2D of Hu5F9-G4 (magrolimab), and will enroll 6-18 patients.  A formal 
amendment is required to proceed to the phase 2 portion of the protocol.  The phase 2 portion 
will be an open label, randomized, two-arm design with for patients with relapsed/refractory MF 
or SS, randomized 1:1 to either mogamulizumab alone or mogamulizumab plus Hu5F9- G4 
(magrolimab), and will enroll 82 patients.   
 
The primary endpoint for the randomized phase 2 portion will be ORR6 – a composite endpoint 
of both response rate and duration of response.  As a historical reference, the ORR6 of the 
intention-to-treat analysis of mogamulizumab arm of the MAVORIC trial was 21%. 
 
Phase 1b Design Operating Characteristics:   The phase 1b 6+3 clinical trial design has the 
following operating characteristics.  
 
 
No Dose L1 
L2 
Months to Complete 
(mean, median, 
range) 
Number of evaluable 
patients treated 
(mean, median, 
range) 
True DLT 
Probability 
- 
0.1 
0.15 
- 
 
Prob MTD 3+3 0.03 
0.22 
0.75 
8.4, 7.6 (3.3-22.1) 
6.6, 6 (4-12) 
Prob MTD 6+3 0.01 
0.13 
0.86 
6.5, 5.6 (2.0-25.1) 
6.9, 6 (5-18) 
 
 
 
 
 
 
True DLT 
Probability 
- 
0.1 
0.3 
 
 
Prob MTD 3+3 0.08 
0.53 
0.39 
9.9, 9.5 (3.5-26.2) 
8.0,8.0 (4-12) 

 
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Prob MTD 6+3 0.03 
0.49 
0.48 
8.6, 8.1 (2.0-25.3) 
9.4,9.0 (5-18) 
 
 
 
 
 
 
True DLT 
Probability 
- 
0.2 
0.4 
 
 
Prob MTD 3+3 0.32 
0.49 
0.19 
10.2, 9.8 (3.2-26.2) 
8.4,8.0 (4-12) 
Prob MTD 6+3 0.20 
0.55 
0.25 
  9.7, 9.2 (2.1-24.2) 
10.8,11.0 (5-18) 
 
 
 
 
 
 
True DLT 
Probability 
- 
0.3 
0.5 
 
 
Prob MTD 3+3 0.59 
0.33 
0.08 
9.5, 9.2 (2.5-23.2) 
8.0,8.0 (4-12) 
Prob MTD 6+3 0.47 
0.42 
0.10 
9.9, 9.5 (2.2-24.3) 
11.3, 11 (5-18) 
 
These estimates are based on 800 simulations, and assume a 30% screen failure, and a 20% 
inevaluable rate (see oneq.netlify.app for simulation engine).  The study starts on dose level 2 
and only de-escalates if required based on the rules (2 DLTs in the traditional 3+3 design, and 3 
DLTs in the 6+3 design).  The simulations assume a 10 day mean interarrival time. As the 6+3 
design does not de-escalate with 2 DLTs out of 6 patients, it tolerates slightly more toxicity than 
the traditional 3+3 design. Specifically, a maximum of 2 out of 9 patients with a DLT (or 22.2%) 
observed toxicity at the MTD is accepted rather than a maximum of 1 out of 6 with a DLT 
(16.7%) with 3+3 design.  These operating characteristics are such that with a 15% DLT rate at 
the starting dose, the MTD will be selected as that dose with 86% probability, and with a 50% 
DLT rate at the starting dose, the MTD will be less than that dose with 90% probability.  The 
rules of the 6+3 determine the maximum tolerated dose, but the RP2D may be the MTD or less 
depending on the severity of the DLTs, sub-DLT level toxicities, later toxicities and clinical 
judgement.  In the phase 2 randomized study, further interim safety analyses are conducted to 
make sure the observed DLT rate does not exceed 30%.     
 
Phase 2 Power and Sample Size:  We anticipate a lower ORR6 response rate for the control 
mogamulizumab arm of this trial to be lower than that for MAVORIC (Kim et al, 2018).  This is 
because mogamulizumab is now FDA-approved and is increasingly being utilizing in the 
treatment of patients with SS in particular, where higher response rates were seen in the 
MAVORIC trial.  Therefore, we anticipate that referrals to this trial will be more skewed towards 
MF than MAVORIC where Sezary patients comprised 45% of the intention-to-treat (ITT) 
population.  We have therefore estimated that the control arm of this cohort will have an ORR6 
of 16% for the purposes of the power calculation, with 30% ORR6 in the SS patients and 10% in 
the MF patients, who we estimate will comprise 70% of the trial (resulting in a combined ORR6 
of 16%).  With 82 patients (41 in each arm), and assuming the 2 strata with SS have an ORR6 of 
30% and the 2 strata with MF have an ORR6 of 10%, and looking to detect an odds ratio of 3.2 
associated with the addition of Hu5F9-G4 (magrolimab), there is 86% power to detect this effect 
size with 41 patients in each treatment arm, with a type I error (one-sided) of 0.15.  The choice of 
the type I error is based on (Rubinstein et al., 2005).  This odds ratio is associated with detecting 
an improvement from 16% to 36% in the ORR6.  This calculation is based on the Mantel-
Haenszel (Cochran) test for 2x2 tables for 4 strata (based on MF vs SS and Stage) and calculated 
with nQuery+nTerim 4.0 (2015).  
In addition, if the Sezary patients are more prevalent than we anticipate, reaching a percentage of 

 
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80 
patients reflected in the MAVORIC trial (45%), the combined ORR6 is 19% and the power 
increases from 86% to 88%.   
 
 
Interim Futility Analysis:  A planned interim futility analysis will be performed as per the 
Wieand rule.  When 50% of the patients are evaluable, if the ORR6 of the combination is not 
superior to the single agent, accrual will hold. 
 
Interim Safety Analysis:   Before proceeding to the Phase 2 study, the Phase 1b will report 
satisfaction of the DLT safety criteria and provide a complete report of adverse events and a 
listing of patients in the Phase 1b that were taken off treatment due to adverse events, and the 
cycles in which that occurred.  During the Phase 2 study, a formal amendment will be considered 
if at any point the first course DLT rate exceeds 30%, inclusive of all Phase 1b/2 patients treated 
at the RP2D on the combination of Hu5F9-G4 (magrolimab) and mogamulizumab, and accrual 
will be held pending review.  Additional toxicity monitoring rules beyond cycle 1 follow: 
 
The grade 3-4 AE rate of mogamulizumab throughout multiple cycles of the MAVORIC study 
was 41% (75 of 184 patients), with 28/184 stopping for AE (15%).   The median PFS was 
approximately 7.7 months.  Two of the three on-treatment deaths with mogamulizumab single 
agent (sepsis and polymyositis) were considered treatment related (2 of 184). 
 
The optimistic scenario is that the combination of Hu5F9-G4 (magrolimab) and mogamulizumab 
will have enhanced activity over single agent mogamulizumab offsetting the potential increased 
toxicity of the doublet over single agent mogamulizumab ab.  It is expected that the toxicity will 
be higher with the doublet, and this will be further amplified if the combination is active, keeping 
patients on treatment longer and increasing the chance of cumulative toxicities and sporadic 
toxicities.  As a result, the rules for toxicity monitoring throughout the study will trigger a 
Toxicity Monitoring Committee (TMC) meeting (members of the TMC will receive the report at 
the time of the trigger and will respond within two weeks of the report of the trigger) to decide 
upon further action based on the totality of the data on both arms.  The Toxicity Monitoring 
Committee will have the authority to hold study accrual and will send a report to the Data 
Coordinating Center, which will also be reviewing severe adverse events and the totality of the 
data at the regularly scheduled intervals (every 6 months) [separate from the monthly data 
coordination center review of data].  The Toxicity Monitoring Committee will consist of the NCI 
drug monitor, the NCI disease monitor, the study PI and the site PI/treating physician, or the 
respective designees for the toxicity committee members.    
 
The triggering rules for Toxicity Monitoring Committee are as follows:     
1) Any treatment-related death on the combination of Hu5F9-G4 (magrolimab) and 
mogamulizumab (considered possibly related) will trigger a Toxicity Monitoring 
Committee meeting.  The request for a Toxicity Monitoring Committee meeting will be 
made within 24 hours of the report of a treatment-related death to the Data Coordinating 
Center.   
2) If the reported data documents at least 2 patients and more than 30% of patients stop 
therapy on the doublet due to adverse events before the third cycle, the Data Coordinating 
Center (which meets monthly) will trigger a Toxicity Monitoring Committee meeting.  If 

 
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83 
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(s) (CAEPRs) 
 
10.1.1 CAEPR for CTEP IND Agent 
 
10.1.1.1 CAEPR for Hu5F9-G4 (magrolimab) 
 
Comprehensive Adverse Events and Potential Risks list (CAEPR) 
for  
Hu5F9-G4 (magrolimab, NSC 809249) 
 
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' 

 
NCI Protocol #:  10384 
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87 
 
4Acute graft-versus-host disease has been observed in patients treated with KW-0761 (mogamulizumab) 
who subsequently received hematopoeitic stem cell transplants. 
 
5Infection may include any of the infection sites under the INFECTIONS AND INFESTATIONS SOC. 
 
6Symptoms of hepatic dysfunction may include Alanine aminotransferase increased, Alkaline 
phosphatase increased, Aspartate aminotransferase increased, Blood bilirubin increased, and GGT 
increased under the INVESTIGATIONS SOC. 
 
 
Adverse events reported on KW-0761 (mogamulizumab) trials, but for which there is insufficient 
evidence to suggest that there was a reasonable possibility that KW-0761 (mogamulizumab) 
caused the adverse event: 
 
BLOOD AND LYMPHATIC SYSTEM DISORDERS - Anemia; Disseminated intravascular coagulation; 
Febrile neutropenia; Hemolysis; Thrombotic thrombocytopenic purpura 
CARDIAC DISORDERS - Atrial fibrillation; Sinus tachycardia; Supraventricular tachycardia 
EYE DISORDERS - Retinal vascular disorder 
GASTROINTESTINAL DISORDERS - Abdominal pain; Cheilitis; Colitis2; Constipation; Diarrhea; 
Gastritis; Mucositis oral; Vomiting 
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS - Chills; Death NOS; Edema 
limbs; Generalized edema; Malaise; Multi-organ failure 
HEPATOBILIARY DISORDERS - Cholecystitis; Hepatic failure; Hepatobiliary disorders - Other (bile duct 
stone); Hepatobiliary disorders - Other (hepatitis) 
INVESTIGATIONS - Blood lactate dehydrogenase increased2; CPK increased; Lipase increased; Serum 
amylase increased; Weight loss 
METABOLISM AND NUTRITION DISORDERS - Acidosis; Anorexia; Dehydration; Hypercalcemia; 
Hyperglycemia; Hyperkalemia; Hypoalbuminemia; Hypocalcemia; Hypokalemia; Hypomagnesemia; 
Hyponatremia; Hypophosphatemia; Metabolism and nutrition disorders - Other (diabetes mellitus) 
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS - Arthralgia; Flank pain; Generalized 
muscle weakness; Musculoskeletal and connective tissue disorder - Other (tendonitis); Myositis 
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS) - Treatment 
related secondary malignancy 
NERVOUS SYSTEM DISORDERS - Depressed level of consciousness; Encephalopathy; Headache; 
Nervous system disorders - Other (altered state of consciousness); Nervous system disorders - Other 
(cerebellar syndrome); Paresthesia; Seizure 
RENAL AND URINARY DISORDERS - Acute kidney injury 
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - Adult respiratory distress syndrome; 
Cough; Dyspnea; Hypoxia; Pleural effusion; Respiratory failure 
SKIN AND SUBCUTANEOUS TISSUE DISORDERS - Alopecia; Dry skin; Erythroderma; Hyperhidrosis; 
Palmar-plantar erythrodysesthesia syndrome; Photosensitivity; Pruritus; Rash acneiform; Skin and 
subcutaneous tissue disorders - Other (lichenoid keratosis); Urticaria 
VASCULAR DISORDERS - Hypertension2; Hypotension2 
 
 
Note: KW-0761 (mogamulizumab) 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. 
 
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 

 
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Version Date:  September 5, 2023 
88 
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. 
 
 
• 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. 
 
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. 
 
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 study 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 
evaluation by completing the Expedited Reporting Evaluation form (i.e., checking the 

 
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89 
box Send All AEs for Evaluation and save the 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/aeguid
elines.pdf. 
 
 
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. 
 
Death due to progressive disease should be reported as Grade 5 “Disease progression” in the 

 
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91 
10.3.4 Additional Protocol-Specific Expedited Adverse Event Reporting Exclusions 
 
For this protocol only, the AEs/grades listed below do not require expedited reporting via CTEP-
AERS.  However, they still must be reported through the routine reporting mechanism (Section 
10.3): 
 
CTCAE SOC 
Adverse Event 
Grades 
≥24h 
Hospitalizationa 
Investigations 
Lymphocyte count decreased 
1-4 
Regardless 
a Indicates that an adverse event required hospitalization for ≥24 hours or prolongation of 
hospitalization by ≥24 hours of a patient. 
 
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. 
 
Adverse event data collection and reporting, which are required as part of every clinical trial, are 
done to ensure the safety of patients enrolled in the studies as well as those who will enroll in 
future studies using similar agents.  AEs are reported in a routine manner at scheduled times 
during the trial using Medidata Rave.  For this trial the Adverse Event CRF is used for routine 
AE reporting in Rave. 
 
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.  
 
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:  
 

 
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92 
• 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.  
 
 
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. 
 
 
 

 
NCI Protocol #:  10384 
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93 
 
11. STUDY CALENDAR 
 
Baseline evaluations are to be conducted within 1 week prior to start of protocol therapy.  Scans 
and x-rays must be done <4 weeks prior to the start of therapy.  In the event that the patient’s 
condition is deteriorating, laboratory evaluations should be repeated within 48 hours prior to 
initiation of the next cycle of therapy. 
 
 
Pre- 
Study 
Prim
ing 
Cycle 1m 
Cycle 2m 
Cycle 3m 
Cycle 4-12n 
End of 
Treatment or 
Progressiona 
Wk 
1 
Wk 
1 
Wk 
2 
Wk 
3 
Wk 
4 
Wk 
1 
Wk 
2 
Wk 
3 
Wk 
4 
Wk 
1 
Wk 
3 
Wk 
1 
Wk 
3 
Hu5F9-G4 (magrolimab) 
 
A 
A 
A 
A 
A 
A 
A 
A 
A 
A 
A 
A 
A 
 
Mogamulizumab 
 
 
B 
B 
B 
B 
B 
 
B 
 
B 
B 
B 
B 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concurrent medsb 
X---------------------------------------------------------------------------------------------X 
 
X 
Physical exam 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
X 
 
 
 
X 
 
 
 
X 
 
X 
 
 
Performance statusc 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
CBC w/diff, pltsp 
X 
Xp 
Xp 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Comprehensive Chemistry 
Paneld 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Pregnancy teste 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ABO/Rh type and screen, DATl 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Antibody Screenl 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Extended RBC phenotyping 
including minor antigens such 
as CcDEe, Cw, MNSs, Kk, 
FyaFyb, and Jka Jkbl, q 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse event evaluation 
 
X---------------------------------------------------------------------------------------------X 
X 
mSWAT assessment/medical 
photographyf 
 
X 
 
 
 
 
X 
 
 
 
 
X 
Xf 
 
X 
Imagingg 
X 
 
 
 
 
 
 
 
 
 
 
Xg 
Xg 
 
Xg 
Flow Cytometry 
 
X 
 
 
 
 
 
 
 
 
 
Xh 
Xh 
 
Xh 
FFPE biopsy tissue (optional) 
Xo 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Skin punch biopsiesj 
X 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
X 
Correlative blood collectionk 
X 
 
 
X 
 
 
 
 
 
 
 
X 
X 
 
X 

 
NCI Protocol #:  10384 
Version Date:  September 5, 2023 
94 
 
Pre- 
Study 
Prim
ing 
Cycle 1m 
Cycle 2m 
Cycle 3m 
Cycle 4-12n 
End of 
Treatment or 
Progressiona 
Wk 
1 
Wk 
1 
Wk 
2 
Wk 
3 
Wk 
4 
Wk 
1 
Wk 
2 
Wk 
3 
Wk 
4 
Wk 
1 
Wk 
3 
Wk 
1 
Wk 
3 
A: 
Hu5F9-G4 (magrolimab):  On Priming Week 1 only, a priming dose of 1 mg/kg Hu5F9-G4 (magrolimab) will be given.  Then assigned dose on 
Cycle 1 Day 1, 8, 15, and 22, Cycle 2 Day 1, 8, 15 and 22, Cycle 3+ Day 1, 15.  Cycles are 28 days long. 
B: 
Mogamulizumab: 1mg/kg on Cycle 1 Day 1, 8, 15, and 22, Cycle 2+ Day 1, 15.  Cycles are 28 days long. 
a: 
Off-study evaluation.  Cycle 12 (Week 48) visit may serve as end of treatment/progression visit 
b: 
Starting from cycle 4, concurrent meds will be evaluated first week of every cycle 
c: 
Note:  Performance status evaluations are based on a 4 week cycle.  At minimum, performance status should be evaluated at the beginning of 
 
every cycle. 
d: 
Albumin, alkaline phosphatase, total bilirubin, bicarbonate, BUN, calcium, chloride, creatinine, glucose, potassium, total protein, SGOT [AST], 
SGPT [ALT], sodium. 
e: 
Pregnancy test for women of childbearing potential. 
f: 
Starting from Cycle 6, mSWAT assessment will be performed on the 1st week of every 3rd cycle (i.e. cycle 6, 9, 12, 15, etc.), and at the end of 
treatment or progression.  
g. 
Patients without extracutaneous disease at screening (N0-2 and M0):  scans will be performed at baseline and repeated to confirm global 
PR/CR, at suspicion of PD.  Patients with extracutaneous disease at screening (N3 or Nx or M1):  scans will be performed at baseline, Week 12, 
and then repeated at the end of every 3 cycles (i.e. cycle 6, 9, 12.), to confirm global PR/CR, at suspicion of PD.  Scans at the time of progression 
or at the end of treatment do not need to be repeated if the most recent scan occurred within the past 28 days.  End of cycle scans should be 
performed between Days 15 and 28, or Day 1 of the following cycle.  Either PET/CT or diagnostic CT chest/abdomen/pelvis +/- neck may be 
used.  Visit windows of ± 7 days allowed. 
h. 
Patients with B1 or B2 disease at baseline:  Flow cytometry will be performed at Week 1, Week 12, and then repeated on the 1st week of every 
3rd cycle (i.e. cycle 6, 9, 12).  Flow cytometry will also be performed to confirm global PR/CR, if progression of disease is suspected and at end-of-
treatment.  Patients with B0 disease at baseline:  Flow cytometry will be performed at baseline, to confirm a partial or complete response, if 
progression of disease is suspected, and at end-of-treatment. 
j. 
Biopsies are not required for patients with a complete response in the skin. 
k. 
Correlative blood collection will be performed at baseline, Cycle 1 Week 2, Cycle 3 Week 3, Cycle 6 Week 1, and at PD/EOT.  
l.        ABO/Rh, RBC genotyping, and DAT testing are not required for patients randomized to the mogamulizumab-only arm. This will be done prior to 
crossover to the combination arm if applicable. 
m. 
For  cycle 1 through cycle 3, visit windows of  ± 2 days allowed 
n.       Starting from cycle 4, visit windows of ± 3 days allowed 
o. 
Archival tissue sample within 6 months prior to registration 
 
p.        Within 24 hours prior to each of the first 2 doses of Hu5F9-G4infusion, patients must have a documented hemoglobin level of ≥9 g/dL.  Patients 
who do not meet these criteria must be transfused and have their hemoglobin rechecked to meet the minimum hemoglobin threshold prior to 
administering each of the first 2 doses of Hu5F9-G4.  An additional hemoglobin must be checked 3 to 6 hours after the initiation of the first and 
second doses of Hu5F9-G4. The patient should be transfused as clinically appropriate.  Investigators should consider additional hemoglobin 
monitoring during the first week of treatment in patients with symptoms of anemia or at increased risk for complications of anemia. 
q.       RBC genotyping must be performed if a patient received any RBC or whole blood transfusion within the previous 3 months (unless laboratory has 
availability for special techniques for performing phenotyping for patients with recent transfusion).  This may be performed for all patients in lieu 
of an extended RBC phenotyping. 
 
 
 

 
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12. MEASUREMENT OF EFFECT 
 
Although the clinical benefit of these drugs has not yet been established, the intent of offering 
this treatment is to provide a possible therapeutic benefit, and thus the patient will be carefully 
monitored for tumor response and symptom relief in addition to safety and tolerability.  Patients 
with measurable disease will be assessed by standard criteria.  For the purposes of this study, 
patients should be re-evaluated every 12 weeks.   
 
12.1 
Antitumor Effect – ISCL/USCLC/EORTC Response Criteria for Mycosis Fungoides 
and Sezary Syndrome 
 
12.1.1 Definitions 
 
Evaluable for Adverse Events.  All patients will be evaluable for adverse event evaluation from 
the time of their first treatment. 
 
Evaluable for Response.  All patients who have received at least one cycle of therapy and have 
their disease re-evaluated will be considered evaluable for response (exceptions will be those 
who exhibit objective disease progression prior to the end of Cycle 1 who will also be considered 
evaluable).  Patients on therapy for at least this period and who meet the other listed criteria will 
have their response classified according to the definitions set out below. 
 
Response and progression will be evaluated in this study using the 2011 ISCL/USCLC/EORTC 
Response Criteria for Mycosis Fungoides and Sezary Syndrome (Olsen et al., 2011). 
 
12.1.2 Response and Evaluation Endpoints 
The consensus response criteria for Mycosis Fungoides and Sezary Syndrome incorporates 
evaluation of skin, blood, lymph node, and visceral disease compartments.  
 
Skin.  Skin lesions and erythema will be evaluated using the mSWAT.  During each mSWAT 
assessment, medical photography should be completed as described in Appendix F.  Digital 
copies of the photographs will be retained at sites for quality assurance or secondary review 
purposes.  The mSWAT is an objective, quantitative, severity-weighted method to assess the 
extent of skin lesions. An mSWAT score is derived by measuring each lesion as a percentage of 
total body surface area (%TBSA) and multiplying it by a severity-weighting factor (1 = patch, 2 
= plaque, 4 = tumor). All individual numbers are then added to produce a total score. The 
mSWAT assessment tool is described in Appendix E.  
 
Blood.  Peripheral blood flow cytometry will be used to evaluate circulating malignant T-cells as 
indicated on the Study Calendar.  Flow cytometry will be performed by each institution’s 
standards.   
 
Lymph nodes and Viscera.  Either PET/CT or contrast-enhanced CT of the chest, abdomen, and 
pelvis (+/- neck as clinically indicated) may be used to evaluate response in lymph nodes and 
viscera.  Investigators should utilize the same imaging modality performed for the baseline 
assessment throughout the trial.  Although PET/CT may be utilized, response assessment is 

 
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performed through sum of the product of diameters for measureable lesions and therefore it is 
encouraged to also obtain a diagnostic CT along when PET imaging is performed. 
The Investigator will identify, prospectively, the lesions to be followed to evaluate the subject’s 
response to therapy. Lymph nodes must be > 15 mm in the long axis (greatest transverse 
diameter, GTD) or > 10 mm in the short axis if the GTD is > 10 to ≤ 15 mm. Lymph node 
biopsies may be performed, at the discretion of the Investigator, to rule out inflammation or to 
confirm disease. Analysis of these biopsies will be done by the pathologist at the study site. 
 
12.1.3 Response Criteria   
 
Response in each compartment will be assessed by the following criteria. 
Response in Skin* 
Complete response (CR) 100% clearance of skin lesions# 
Partial response (PR) 
50-99% clearance of skin disease from baseline without new 
tumors (T3) in subjects with T1, T2 or T4 only skin disease 
Stable disease (SD) 
<25% increase to <50% clearance in skin disease from baseline 
without new tumors (T3) in subjects with T1, T2 or T4 only skin 
disease 
Progressive disease 
(PD)† 
(1) >25% increase in skin disease from baseline or 
(2) New tumors (T3) in subjects with T1, T2 or T4 only skin disease 
or 
(3) Loss of response: in those with CR or PR, increase of skin score 
of greater than the sum of nadir plus 50% baseline score 
Relapse 
Any disease recurrence in those with CR 
*Based on mSWAT score. 
# A biopsy of normal appearing skin is unnecessary to assign a CR. However, a skin biopsy 
should be performed of a representative area of the skin if there is any question of residual 
disease where otherwise a CR would exist. If histologic features are suspicious or suggestive of 
Mycosis Fungoides/Sézary Syndrome (see histologic criteria for early MF7), the response should 
be considered a PR only. 
†Whichever criterion occurs first. 
  
Response in Blood* 
CR* 
B0 
PR** 
>50% decrease in quantitative measurements of blood tumor burden from baseline 
in those with high tumor burden at baseline (B2) 
SD 
Fails to attain criteria for CR, PR or PD 
PD† 
(1) B0 to B2 or 
(2) >50% increase from baseline and at least 5,000 neoplastic cells/μL or 
(3) Loss of response: 
in those with CR who were B1 or B2 at baseline, increase in neoplastic >1000 
neoplastic cells/ μL or 
in those with PR who were originally B2 at baseline, >50% increase from nadir 
and at least 5,000 neoplastic cells/μL 
Relapse 
Increase of neoplastic blood lymphocytes to ≥B1 in those with CR 
* As determined by absolute numbers of neoplastic cells/uL. 

 
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** There is no PR in those with B1 disease at baseline as the difference within the range of 
neoplastic cells that define B1 is not considered significant and should not affect determination 
of global objective response. 
†Whichever occurs first. 
 
Response in Lymph Nodes* 
CR 
All lymph nodes are now <1.5 cm in greatest transverse (long axis) diameter by method 
used to assess lymph nodes at baseline or biopsy negative for lymphoma. In addition, 
lymph nodes that were N3 classification and <1.5 cm in long axis diameter at baseline, 
must now be <1 cm in diameter of the short axis or biopsy negative for lymphoma 
PR 
(1) Cumulative reduction >50% of the SPD [sum of the maximum linear dimension 
(major axis) x longest perpendicular dimension (minor axis) of each abnormal lymph 
node at baseline and no new lymph node >1.5 cm or >1.0 cm in the short axis if long axis 
1-1.5cm diameter. 
SD 
Fails to attain the criteria for CR, PR and PD 
PD† 
(1) >50% increase in SPD from baseline of lymph nodes or 
(2) Any new node >1.5 cm in greatest transverse diameter or >1 cm in short axis diameter 
if 1-1.5 cm in long axis that is proven to be N3 histologically or 
(3) Loss of response: in those with PR or CR, >50% increase from nadir in SPD of lymph 
nodes 
Relapse 
Any new lymph node >1.5cm in long axis diameter in those with CR 
* Peripheral and central lymph nodes. 
†Whichever criterion occurs first. 
 
Response in Viscera 
CR 
Liver or spleen or any organ considered involved at baseline should not be enlarged on 
physical exam and should be considered normal by imaging. No nodules should be 
present on imaging of liver or spleen. Any post treatment mass must be determined to be 
biopsy to be negative for lymphoma 
PR 
>50% regression in any splenic or liver nodules, or in measurable disease (SPD) in any 
organs abnormal at baseline. No increase in size of liver or spleen and no new sites of 
involvement. 
SD 
Fails to attain the criteria for CR, PR or PD 
PD† 
(1) >50% increase in size (SPD) of any organs involved at baseline or 
(2) New organ involvement or 
(3) Loss of response: in those with PR or CR, >50% increase from nadir in the size 
(SPD) of any previous organ involvement 
Relapse 
New organ involvement in those with CR 
†Whichever criterion occurs first. 
 
Global Response: The global response incorporates response assessments from all disease 
compartments.  

 
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Global Response Score 
Global Score 
Definition 
Skin 
Nodes 
Blood 
Viscera 
CR 
Complete 
disappearance of all 
clinical evidence of 
disease 
CR 
All categories have CR/NI 
PR 
Regression of 
measurable disease 
CR 
All categories do not have a CR/NI and no category 
has a PD 
PR 
No category has a PD and if any other category 
involved at baseline, at least one has a CR or PR 
SD 
Failure to attain 
CR, PR or PD 
representative of all 
disease 
PR 
No category has a PD and if any other category 
involved at baseline, no CR or PR in any 
SD 
CR/NI, PR, SD in any category and no category has a 
PD 
PD 
Progressive disease 
PD in any category 
Relapse 
Recurrence disease 
in prior CR 
Relapse in any category 
NI= noninvolved 
 
 
12.1.4 Confirming early progression:  
 
Immunotherapeutics may result in infiltration of immune cells leading to transient increase in the 
size in malignant lesions, or undetectable lesions becoming detectable. In cutaneous lymphoma 
this may manifest as worsening appearance of skin lesions or lymph nodes early in treatment.  
To allow sufficient time to differentiate such pseudoprogression from true progression, patients 
with early progression events may continue on treatment with increased surveillance until true 
progression is confirmed.  Treatment beyond progression in such cases can occur at the 
investigator’s discretion after approval by the Principal Investigator.  
 
Skin progression: Patients with progression in the skin compartment documented any time up to, 
and including, their assessment at 12 weeks may continue on treatment if they meet all of the 
following criteria: 
1. Progression cannot be due to development of new tumors (T3) disease in a patient with 
T1, T2, or T4 disease 
2. Patients must have monthly mSWAT assessments while continuing treatment 
3. During this period of unconfirmed progression, the mSWAT score on each subsequent 
assessment must be less than or equal to the most recent mSWAT score (i.e. the 
mSWAT must improve with each subsequent evaluation) 
 
It is strongly encouraged that a skin biopsy be performed if the investigator suspects 
pseudoprogression in the skin.  The patient may continue with monthly mSWAT examinations 
until Cycle 6.  By Cycle 6, the patient must meet criteria for stable disease or better to continue 
on treatment.  If progression is confirmed by an increase in mSWAT in a subsequent evaluation, 
then the date of progression for endpoint analysis will be the first date of progression, not the 

 
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date of the confirmation. 
 
Lymph node:  Patients with progression in the lymph node compartment documented on their 
first scheduled assessment at 12 weeks may continue on treatment if they meet the following 
criteria: 
1. Either a biopsy must be performed of a progressing lymph node (preferred), or a repeat 
scan must be performed in 4-8 weeks after the week 12 scan showing progression 
2. If a biopsy is performed on a progressing lesion, it must show changes consistent with 
pseudoprogression.   
3. If a biopsy cannot be performed, then a subsequent scan performed 4-8 weeks later must 
have an SPD less than or equal to the week 12 scan.  If progression was due to the 
appearance of new assessable lymph nodes, all new lymph nodes must be equal or 
smaller in cross-sectional area to their measurements on the week 12 scan 
 
If a follow up scan performed 4-8 weeks later shows improvement, then the patient can continue 
on the treatment protocol until the next planned assessment at Cycle 6.  All patients must have a 
lymph node response of SD or better on their Cycle 6 imaging assessment to continue on 
treatment protocol.   
 
If progression is confirmed by imaging evaluation on either the scan performed 4-8 weeks later 
or their Cycle 6 imaging, then the date of progression for endpoint analysis will be the first date 
of progression, not the date of the confirmation scan. 
 
If the repeat evaluations do not confirm progression, the patient will continue to be treated and 
evaluated as per the original study calendar.  
 
 
12.2 
Definitions of Study Endpoints 
Overall Response Rate (ORR): ORR is defined as the proportion of patients who have a partial or 
complete response to therapy as defined by the global response score. 
 
Duration of Response (DOR): DOR is defined as the duration of overall response is measured 
from the time measurement criteria are met for CR or PR (whichever is first recorded) until the 
first date that recurrence or PD is objectively documented. 
 
Overall Response Rate 4 (ORR4): ORR4 is defined as the proportion of patients who have a 
partial or complete response to therapy AND a duration of response ≥ 4 months. 
 
Overall Response Rate 6 (ORR6): ORR6 is defined as the proportion of patients who have a 
partial or complete response to therapy AND a duration of response ≥ 6 months. 
 
Overall Response Rate 12 (ORR12): ORR12 is defined as the proportion of patients who have a 
partial or complete response to therapy AND a duration of response ≥ 12 months. 
 
Progression-Free Survival (PFS):  PFS is defined as the duration of time from start of treatment 
to time of progression or death, whichever occurs first. 

 
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Time to next treatment (TTNT): TTNT is defined as the duration of time from the start of 
treatment on this protocol to time of the next anti-neoplastic therapy. 
 
 
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.   
 
For the Phase 1 portion of this study, all decisions regarding dose escalation/expansion/de-
escalation require sign-off by the Protocol Principal Investigator through the CTMS/IWRS.  In 
addition, for the Phase 1 portion, the Protocol Principal Investigator will have at least monthly, 
or more frequently, conference calls with the Study Investigators and the CTEP Medical 
Officer(s) to review accrual, progress, and adverse events and unanticipated problems.  
 
For a Phase 1/2 trial, enrollment to the Phase 2 portion of the trial will not begin until a protocol 
amendment has been submitted which summarizes the Phase 1 results, the recommended Phase 2 
dose, and the rationale for selecting it.  The amendment must be reviewed and approved by 
CTEP before enrollment to the Phase 2 portion can begin. 
 
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 the 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.   
Requirements to access Rave via iMedidata: 
 

 
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• 
Active CTEP registration with credentials necessary to access secure NCI/CTSU IT 
systems, 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 a Non-Physician Investigator 
(NPIVR) or Investigator (IVR), and 
o Rave Read Only or Rave SLA role 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 Delegation of Tasks Log (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 the Regulatory applicatin, 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 who have not previously activated their iMedidata/Rave account at the time of initial 
site registration approval for the study in the Regulatory application 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 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 
http://www.theradex.com/clinicalTechnologies/?National-Cancer-Institute-NCI-11.  On-site 

 
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audits will be conducted three times annually (one annual site visit and two data audits).  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 
(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/adverse_events.htm). 
 

 
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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.  Site staff should 
review the DQP modules on a regular basis to manage specified queries and delinquent 
forms. 
 
The DQP is accessible by site staff who are rostered to a site and have access to the 
CTSU website.  Staff who have Rave study access can access the Rave study data via 
direct links available on the DQP modules. 
 
CTSU Delinquency Notification emails are sent to primary contacts at sites twice a 
month. These notifications serve as alerts that queries and/or delinquent forms require 
site review, providing a summary count of queries and delinquent forms for each Rave 
study that a site is participating in. Additional site staff can subscribe and unsubscribe to 
these notifications using the CTSU Report and Information Subscription Portal on the 
CTSU members’ website. 
 
To learn more about DQP use and access, click on the Help Topics button displayed on 
the Rave Home, DQP Queries, DQP Delinquent Forms, DQP Form Status, and DQP 
Reports modules. 
 
13.4 
CTEP Multicenter Guidelines 
 
N/A 
 
13.5 
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.  

 
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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. 
 
2. For a clinical protocol where there is an investigational Agent used in combination with 
(an)other Agent(s), each the subject 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 subjects, 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 

 
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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 
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. 
 
13.6 
Genomic Data Sharing Plan 
 
We will share anonymized genomic sequence data (whole exome sequencing and RNA 
sequencing) from all subjects by depositing these data in the database of Genotypes and 
Phenotypes (dbGaP) (a controlled-access database funded by NIH). The genotype data will be 
made publicly available no later than the date of initial publication or twelve months after 
completion of sequencing. 
 
13.7 
Incidental/Secondary Findings Disclosure Procedure 
 
There are no planned analysis to detect medically important genomic features other than 
potential biomarkers for the protocol therapies.  There will be no planned disclosure of 
incidental/secondary genomic findings.   The informed consent form will disclose that the 
subject will not be contacted about potential medically important findings.   
 
 

 
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14. CALIFORNIA CANCER CONSORTIUM (CCC) POLICIES FOR MONITORING 
CONSORTIUM TRIALS 
 
This protocol is monitored at several levels, as described in this section.  To summarize:  The 
trial PI has access to the data at all times.  The CCC Data Coordinating Center reviews accrual 
and toxicities monthly.  An external, independent DSMC reviews the study progress twice 
yearly.  In addition, for the Phase 1 portion, the study PI will have monthly, and as needed, 
conference calls with study investigators to review accrual, progress, and any unforeseen issues.  
Dose escalation/expansion/de-escalation decisions require sign-off by the study PI (or his or her 
designee) and study statistician (or his or her designee).  During the Phase 2 portion, the study PI 
will have quarterly, and as needed, conference calls with study investigators and CTEP Medical 
Officer(s) to review accrual, progress, pharmacovigilance, and any unforeseen issues.  Decisions 
to proceed to the second stage of the Phase 2 trial will require sign-off by the study PI and the 
trial statistician. 
 
The protocol PI is responsible for monitoring the conduct and progress of this Phase 2 trial, 
including the ongoing review of accrual, data, and toxicities, as well as the accumulation of 
reported AEs from other trials testing the same drugs.  The participating clinicians and their 
designees are responsible for timely submission of AE reports (see Section 10.0) and electronic 
CRFs.  The Data Coordinating Center for the CCC Consortium is responsible for providing the 
PI with access to the submitted CRF data in summary and detail in a timely fashion.   Although 
the PI is responsible for evaluating the cumulative reported AEs and the impact that these have 
on the continued conduct of the trial, it is the Data Coordinating Center of the CCC that 
distributes all submitted SAE reports to the appropriate individuals, including the local protocol 
PIs, at each of the participating institutions. 
 
The Data Coordinating Center posts a summary (accrual, toxicities, and responses) of each CCC 
initiated trial on the CCC website.  In this way, each PI has access to up-to-date information on 
the status of his or her trial.  In consultation with the collaborating statistician, the PI is 
responsible for review of: 
 
− 
for Phase 1 trials, all DLTs and decisions regarding dose escalation, expansion, as well as 
decisions to terminate escalation, and  
− 
for Phase 2 trials, the toxicities and therapeutic endpoints referred to in the statistical 
plan. 
 
The Data Coordinating Center meets monthly to review data management and data quality 
issues, including completeness of data submissions and accuracy in terms of built-in, 
computerized logic checks.  Any issues identified, and subsequent corrective plans are presented 
to the Internal Committee and at the next CCC teleconference meeting for review and approval. 
 
 
 

 
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previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, 
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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 B 
FORMULA TO ESTIMATE RENAL FUNCTION USING SERUM 
CREATININE 
 
Formulas to estimate renal function using serum creatinine provided by the NCI’s Investigational 
Drug Steering Committee (IDSC) Pharmacological Task Force in table below. 
 
1. Estimated creatinine clearance (ClCr) by the Cockcroft-Gault (C-G) equation (Cockcroft and 
Gault, 1976). 
 
 
Followed by conversion to a value normalized to 1.73 m2 with the patient’s body surface area 
(BSA). 
 
References 
1. Cockcroft, D.W. and M.H. Gault.  (1976).  Prediction of creatinine clearance from serum 
creatinine.  Nephron.  16:31-41. 
 

 
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APPENDIX D 
TISSUE BIOPSY VERIFICATION 
 
A completed copy of this appendix (i.e., Tissue Biopsy Verification) must be submitted to 
the EET Biobank. 
 
Note: If this information is not provided with the biopsy specimen, then it will not be accepted 
by the EET Biobank. 
 
 
 
Please have the Clinician* responsible for signing out this patient’s case complete the following: 
 
ETCTN Universal Patient ID:  
 
 
ETCTN Patient Study ID:   
 
 
Date of Procedure (mm/dd/yyyy):   
 
 
Tissue Type (circle one): 
Skin 
 
Time point (circle one):  Baseline 
C1W2 
C3W3 
 
End of Treatment/Progression 
 
Site(s) Tissue Taken From:   
 
 
Diagnosis:   
 
 
I agree that this tissue may be released for research purposes only and that the release of this 
tissue will not have any impact on the patient’s care. 
 
 
 
Clinician Signature 
Date 
 
 
 
Clinician Printed Name 
 
*Note: For the purposes of this form, Clinician could include the Nurse Practitioner, Registered Nurse, Pathologist, 
Radiologist, Interventional Radiologist, Surgeon, Oncologist, Internist, or other medical professional responsible for 
the patient’s care.  

 
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APPENDIX E:  MODIFIED SEVERITY-WEIGHTED ASSESSMENT TOOL (MSWAT) 
 
The mSWAT is an objective, quantitative, severity- weighted method to assess the extent of 
Mycosis Fungoides lesions. A SWAT score is derived by measuring each lesion as a percentage 
of total body surface area (%TBSA) and multiplying it by a severity-weighting factor (1 = patch, 
2 = plaque, 4 = tumor). All individual numbers are then added to produce a total score. 
The body is divided into 12 regions with pre-assigned %TBSA based on methodology used to 
assess burns. The extent of skin disease is assessed for each region and quantified by using the 
subject’s palm as a “ruler” to measure the %TBSA involvement within each region. 
Subject’s palm with 4 fingers, including the thumb and measured from wrist to fingertips, is 1% 
of TBSA. 
Subject’s palm without fingers is 0.5% of TBSA. 
Modified Severity Weighted Assessment Tool 
Modified Severity Weighted Assessment Tool 
Mycosis Fungoides lesion 
type 
Elevation description 
Erythema description 
Patch 
Abnormal skin not elevated from 
normal skin 
Flat erythema or erythema with mild 
infiltration 
Plaque 
Abnormal skin elevated from normal 
skin by <5 mm 
Elevated erythema or erythema with 
moderate infiltration 
Tumor 
Abnormal skin elevated from normal 
skin by ≥5 mm 
Erythema with fissuring, ulceration, or 
tumor 
SWAT Score Calculation 
 
 
Sum of %TBSA from all body regions affected by patches x severity weighted factor of 1 
+ Sum of %TBSA from all body regions affected by plaques x severity weighted factor of 2 
+ Sum of %TBSA from all body regions affected by tumors x severity weighted factor of 4 
= TOTAL SWAT: (maximum score = 400) 
 
 
 

 
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Modified Severity Weighted Assessment Tool 
Body region (%BSA) 
Patch* 
Plaque* 
Tumor* 
Head (7%) 
 
 
 
Neck (2%) 
 
 
 
Anterior trunk (13%) 
 
 
 
Arms (8%) 
 
 
 
Forearms (6%) 
 
 
 
Hands (5%) 
 
 
 
Posterior trunk (13%) 
 
 
 
Buttocks (5%) 
 
 
 
Thighs (19%) 
 
 
 
Legs (14%) 
 
 
 
Feet (7%) 
 
 
 
Groin (1%) 
 
 
 
Subtotal of lesion BSA 
 
 
 
Weighting factor 
x1 
x2 
x4 
Subtotal lesions BSA x weighting factor 
 
 
 
mSWAT score (summation of each column line above) =  
 
 
patch = any size lesion without induration or significant elevation above the surrounding uninvolved skin: 
poikiloderma may be present. 
 
plaque = any size lesion that is elevated or indurated; crusting, ulceration or poikiloderma may be present. 
 
tumor = any solid or nodular lesion ≥ 1 cm in diameter with evidence of deep infiltration in the skin and/or vertical 
growth.
 

 
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APPENDIX F:  STANDARDIZED MEDICAL PHOTOGRAPHY 
 
Using a standard medical blue background and with the patient in anatomical position (palms 
placed anteriorly), the following photos will be taken of the study participant: 
1. Global (full body). 
2. Half-global (half body – anterior and posterior aspect). 
3. Additional photographs will be taken at a short distance (1 foot) of biopsy sites.