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Trial of Magrolimab (Hu5F9-G4) in Combination With Rituximab or Rituximab + Chemotherapy in Participants With Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma

Primary Purpose

Non Hodgkin Lymphoma

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Magrolimab
Rituximab
Gemcitabine
Oxaliplatin
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non Hodgkin Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

  • Phase 1b only: B-cell non-Hodgkin's lymphoma (NHL), relapsed or refractory to standard approved therapies
  • DLBCL Phase 2 cohort: De novo or transformed diffuse large B-cell lymphoma (DLBCL) expressing CD 20, relapsed or refractory to at least 2 prior lines treatment containing anti-CD20 therapy
  • Indolent lymphoma Phase 2 cohort: Marginal zone or follicular lymphoma, relapsed or refractory to standard approved therapies
  • DLBCL chemotherapy combination cohort: De novo or transformed diffuse large B-cell lymphoma (DLBCL), relapsed or refractory to 1-3 prior lines of treatment
  • Adequate performance status and hematological, liver and kidney functions
  • Willing to consent to 1 mandatory pre-treatment and 1 on-treatment tumor biopsy

Key Exclusion Criteria:

  • Active brain metastases
  • Prior allogeneic hematopoietic cell transplantation
  • Prior treatment with CD47 or signal regulatory protein alpha (SIRPα) targeting agents
  • Second malignancy within the last 3 years
  • Known active or chronic hepatitis B or C infection or HIV
  • Pregnancy or active breastfeeding
  • Prior chimeric antigen receptor (CAR-T) therapy

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Sites / Locations

  • University of Alabama At Birmingham (Uab)
  • City of Hope National Medical Center
  • Stanford Cancer Center
  • Georgia Cancer Center at Augusta University
  • University of Chicago Medical Center
  • National Institutes of Health Clinical Center/ National Cancer Institute
  • Beth Israel Deaconess Medical Center
  • Dana Farber Cancer Institute
  • University of Michigan
  • University of Minnesota Medical Center, Fairview
  • Washington University School of Medicine Siteman Cancer Center
  • Levine Cancer Institute
  • Stephenson Cancer Center
  • Hospital of the University of Pennsylvania
  • The Sarah Cannon Research Institute
  • The University of Texas MD Anderson Cancer Center
  • Princess Alexandra Hospital
  • St. Vincent's Hospital Melbourne
  • Linear Clinical Research Ltd
  • The Churchill Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Magrolimab + Rituximab, Phase 1b Dose Escalation

Magrolimab + Rituximab, Phase 2 Indolent Lymphoma

Magrolimab + Rituximab, Phase 2 Diffuse Large B-Cell lymphoma

Magrolimab + R-GemOx, Phase 1b Safety Dose Escalation Phase

Magrolimab + R-GemOx, Phase 1b Dose Expansion Phase

Arm Description

Participants with B-cell non-Hodgkin's lymphoma will receive 1 mg/kg magrolimab priming dose on Day 1 of Cycle 1 followed by weekly maintenance doses of 10, 20, 30, or 45 mg/kg on Days 8, 15, 22 for Cycle 1 and Days 1, 8, 15, and 22 for each cycle to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose and schedule (RP2DS) in combination with rituxumab 375 mg/m^2. Cycle length is 28 days.

Participants with indolent lymphoma will receive magrolimab based on RP2DS from Phase 1b portion of the study in combination with rituxumab 375 mg/m^2.

Participants with diffuse large B-cell lymphoma (DLBCL) will receive magrolimab based on RP2DS from Phase 1b portion of the study in combination with rituxumab 375 mg/m^2.

Autologous stem cell transplant (or transplantation) ineligible DLBCL participants will receive 1 mg/kg magrolimab priming dose on Day 1 for Cyle 1 followed by maintenance doses of 30 or 45 mg/kg on Days 8, 11, 15, 22, and 29 for Cycle 1, every week for Cycle 2, and every 2 weeks for each cycle to determine maximum tolerated dose (MTD) + rituxumab 375 mg/m^2 + gemcitabine 1000 mg/m^2 + oxaliplatin 100 mg/m^2. Cycle length is 28 days.

Autologous stem cell transplant (or transplantation) ineligible DLBCL participants will receive magrolimab at a dose determined from Phase 1b Safety Dose-Escalation Phase in combination with rituxumab 375 mg/m^2 + gemcitabine 1000 mg/m^2 + oxaliplatin 100 mg/m^2.

Outcomes

Primary Outcome Measures

Phase 1b: Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs)
DLTs refer to toxicities experienced during the first 28 days of study treatment that have been judged to be clinically significant and related to study treatment in participant in Phase 1b.
Percentage of Participants Experiencing Treatment Emergent Adverse Events
Objective Response Rate as Defined by the Investigator According to the Lugano Classification for Lymphomas
Objective response is defined as complete response (CR) + partial response (PR) determined by Lugano classification for lymphomas.

Secondary Outcome Measures

PK Parameter of Magrolimab: AUClast
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
PK Parameter of Rituximab: AUClast
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
PK Parameter of Magrolimab: AUCtau
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
PK Parameter of Rituximab: AUCtau
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
PK Parameter of Magrolimab: Cmax
Cmax is defined as the maximum observed concentration of drug.
PK Parameter of Rituximab: Cmax
Cmax is defined as the maximum observed concentration of drug.
Percentage of Participants who Developed Anti-Magrolimab Antibodies
Duration of Response
The duration of response is measured from when the first (objective) response is met (i.e., complete response or partial response) until the first date of objectively documented progressive disease.
Progression Free Survival
Progression free survival is measured from dose initiation until the first date of objectively documented disease progression or death.
Overall Survival
Overall Survival is measured from dose initiation until death.
Time to Progression
Time to Progression is measured from dose initiation until the first date of objectively documented progressive disease criteria.
Objective Rate of Response Defined by the Investigator According to the LYRIC Criteria for Lymphomas
Objective response is defined as complete response + partial response determined by Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) criteria.

Full Information

First Posted
November 1, 2016
Last Updated
October 13, 2023
Sponsor
Gilead Sciences
Collaborators
The Leukemia and Lymphoma Society
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1. Study Identification

Unique Protocol Identification Number
NCT02953509
Brief Title
Trial of Magrolimab (Hu5F9-G4) in Combination With Rituximab or Rituximab + Chemotherapy in Participants With Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma
Official Title
A Phase 1b/2 Trial of Hu5F9-G4 in Combination With Rituximab or Rituximab + Chemotherapy in Patients With Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 21, 2016 (Actual)
Primary Completion Date
August 2024 (Anticipated)
Study Completion Date
August 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
Collaborators
The Leukemia and Lymphoma Society

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The primary objectives of this study are: To investigate the safety and tolerability, and to define the recommended Phase 2 dose and schedule (RP2DS) for magrolimab in combination with rituximab and for magrolimab in combination with rituximab, gemcitabine, and oxaliplatin (R-GemOx). To evaluate the efficacy of magrolimab in combination with rituximab in participants with indolent lymphoma and diffuse large B-cell lymphoma (DLBCL) and to evaluate the efficacy of magrolimab in combination with R-GemOx in autologous stem cell transplant (ASCT) ineligible DLBCL participants.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Hodgkin Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
178 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Magrolimab + Rituximab, Phase 1b Dose Escalation
Arm Type
Experimental
Arm Description
Participants with B-cell non-Hodgkin's lymphoma will receive 1 mg/kg magrolimab priming dose on Day 1 of Cycle 1 followed by weekly maintenance doses of 10, 20, 30, or 45 mg/kg on Days 8, 15, 22 for Cycle 1 and Days 1, 8, 15, and 22 for each cycle to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose and schedule (RP2DS) in combination with rituxumab 375 mg/m^2. Cycle length is 28 days.
Arm Title
Magrolimab + Rituximab, Phase 2 Indolent Lymphoma
Arm Type
Experimental
Arm Description
Participants with indolent lymphoma will receive magrolimab based on RP2DS from Phase 1b portion of the study in combination with rituxumab 375 mg/m^2.
Arm Title
Magrolimab + Rituximab, Phase 2 Diffuse Large B-Cell lymphoma
Arm Type
Experimental
Arm Description
Participants with diffuse large B-cell lymphoma (DLBCL) will receive magrolimab based on RP2DS from Phase 1b portion of the study in combination with rituxumab 375 mg/m^2.
Arm Title
Magrolimab + R-GemOx, Phase 1b Safety Dose Escalation Phase
Arm Type
Experimental
Arm Description
Autologous stem cell transplant (or transplantation) ineligible DLBCL participants will receive 1 mg/kg magrolimab priming dose on Day 1 for Cyle 1 followed by maintenance doses of 30 or 45 mg/kg on Days 8, 11, 15, 22, and 29 for Cycle 1, every week for Cycle 2, and every 2 weeks for each cycle to determine maximum tolerated dose (MTD) + rituxumab 375 mg/m^2 + gemcitabine 1000 mg/m^2 + oxaliplatin 100 mg/m^2. Cycle length is 28 days.
Arm Title
Magrolimab + R-GemOx, Phase 1b Dose Expansion Phase
Arm Type
Experimental
Arm Description
Autologous stem cell transplant (or transplantation) ineligible DLBCL participants will receive magrolimab at a dose determined from Phase 1b Safety Dose-Escalation Phase in combination with rituxumab 375 mg/m^2 + gemcitabine 1000 mg/m^2 + oxaliplatin 100 mg/m^2.
Intervention Type
Drug
Intervention Name(s)
Magrolimab
Other Intervention Name(s)
Hu5F9-G4
Intervention Description
Administered intravenously
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
RITUXAN®, MabThera
Intervention Description
Administered intravenously on Days 8, 15, and 22 during Cycle 1, followed by 1 dose on Day 1 for Cycles 2 through 6, and Day 1 for every other cycle until Cycle 13
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Other Intervention Name(s)
Gemzar®
Intervention Description
Administered intravenously on Days 11, 23 for Cycle 1 and Days 2 and 15 for Cycles 2 to 4
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Other Intervention Name(s)
Eloxatin®
Intervention Description
Administered intravenously on Days 11, 23 for Cycle 1 and Days 2 and 15 for Cycles 2 to 4
Primary Outcome Measure Information:
Title
Phase 1b: Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs)
Description
DLTs refer to toxicities experienced during the first 28 days of study treatment that have been judged to be clinically significant and related to study treatment in participant in Phase 1b.
Time Frame
Up to 28 days
Title
Percentage of Participants Experiencing Treatment Emergent Adverse Events
Time Frame
First dose date up to 5 years
Title
Objective Response Rate as Defined by the Investigator According to the Lugano Classification for Lymphomas
Description
Objective response is defined as complete response (CR) + partial response (PR) determined by Lugano classification for lymphomas.
Time Frame
Up to 5 months
Secondary Outcome Measure Information:
Title
PK Parameter of Magrolimab: AUClast
Description
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Time Frame
Before magrolimab infusion (within 12 hours) on Day 1, 8, and 15 of Cycle 1, Day 1 and 15 of Cycle 2, Day 1 of Cycles 3, 4, 5, 9, and 13 and until safety follow-up visit (30 days ± 7 days after last dose of magrolimab); Cycle length is 28 days
Title
PK Parameter of Rituximab: AUClast
Description
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Time Frame
Before rituximab infusion (within 12 hours) on Day 8 and 15 of Cycle 1, Day 1 of Cycle 2, Day 1 of Cycles 3 - 6; Cycle length is 28 days
Title
PK Parameter of Magrolimab: AUCtau
Description
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Time Frame
Before magrolimab infusion (within 12 hours) on Day 1, 8, and 15 of Cycle 1, Day 1 and 15 of Cycle 2, Day 1 of Cycles 3, 4, 5, 9, and 13 and until safety follow-up visit (30 days ± 7 days after last dose of magrolimab); Cycle length is 28 days
Title
PK Parameter of Rituximab: AUCtau
Description
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Time Frame
Before rituximab infusion (within 12 hours) on Day 8 and 15 of Cycle 1, Day 1 of Cycle 2, Day 1 of Cycles 3 - 6; Cycle length is 28 days
Title
PK Parameter of Magrolimab: Cmax
Description
Cmax is defined as the maximum observed concentration of drug.
Time Frame
Before magrolimab infusion (within 12 hours) on Day 1, 8, and 15 of Cycle 1, Day 1 and 15 of Cycle 2, Day 1 of Cycles 3, 4, 5, 9, and 13 and until safety follow-up visit (30 days ± 7 days after last dose of magrolimab); Cycle length is 28 days
Title
PK Parameter of Rituximab: Cmax
Description
Cmax is defined as the maximum observed concentration of drug.
Time Frame
Before rituximab infusion (within 12 hours) on Day 8 and 15 of Cycle 1, Day 1 of Cycle 2, Day 1 of Cycles 3 - 6; Cycle length is 28 days
Title
Percentage of Participants who Developed Anti-Magrolimab Antibodies
Time Frame
Day 1 of Cycle 1 to 5, Day 1 Cycle 9, 13, and until safety follow-up visit (30 days ± 7 days after last dose of magrolimab); Cycle length is 28 days
Title
Duration of Response
Description
The duration of response is measured from when the first (objective) response is met (i.e., complete response or partial response) until the first date of objectively documented progressive disease.
Time Frame
Up to 5 years
Title
Progression Free Survival
Description
Progression free survival is measured from dose initiation until the first date of objectively documented disease progression or death.
Time Frame
Up to 5 years
Title
Overall Survival
Description
Overall Survival is measured from dose initiation until death.
Time Frame
Up to 5 years
Title
Time to Progression
Description
Time to Progression is measured from dose initiation until the first date of objectively documented progressive disease criteria.
Time Frame
First dose date up to 5 years
Title
Objective Rate of Response Defined by the Investigator According to the LYRIC Criteria for Lymphomas
Description
Objective response is defined as complete response + partial response determined by Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) criteria.
Time Frame
Up to 5 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Phase 1b only: B-cell non-Hodgkin's lymphoma (NHL), relapsed or refractory to standard approved therapies DLBCL Phase 2 cohort: De novo or transformed diffuse large B-cell lymphoma (DLBCL) expressing CD 20, relapsed or refractory to at least 2 prior lines treatment containing anti-CD20 therapy Indolent lymphoma Phase 2 cohort: Marginal zone or follicular lymphoma, relapsed or refractory to standard approved therapies DLBCL chemotherapy combination cohort: De novo or transformed diffuse large B-cell lymphoma (DLBCL), relapsed or refractory to 1-3 prior lines of treatment Adequate performance status and hematological, liver and kidney functions Willing to consent to 1 mandatory pre-treatment and 1 on-treatment tumor biopsy Key Exclusion Criteria: Active brain metastases Prior allogeneic hematopoietic cell transplantation Prior treatment with CD47 or signal regulatory protein alpha (SIRPα) targeting agents Second malignancy within the last 3 years Known active or chronic hepatitis B or C infection or HIV Pregnancy or active breastfeeding Prior chimeric antigen receptor (CAR-T) therapy Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama At Birmingham (Uab)
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35924
Country
United States
Facility Name
City of Hope National Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Stanford Cancer Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Georgia Cancer Center at Augusta University
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
National Institutes of Health Clinical Center/ National Cancer Institute
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
University of Minnesota Medical Center, Fairview
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Washington University School of Medicine Siteman Cancer Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Levine Cancer Institute
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Stephenson Cancer Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
The Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Princess Alexandra Hospital
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4102
Country
Australia
Facility Name
St. Vincent's Hospital Melbourne
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3065
Country
Australia
Facility Name
Linear Clinical Research Ltd
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
The Churchill Hospital
City
Oxford
ZIP/Postal Code
OX3 7LE
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
30380386
Citation
Advani R, Flinn I, Popplewell L, Forero A, Bartlett NL, Ghosh N, Kline J, Roschewski M, LaCasce A, Collins GP, Tran T, Lynn J, Chen JY, Volkmer JP, Agoram B, Huang J, Majeti R, Weissman IL, Takimoto CH, Chao MP, Smith SM. CD47 Blockade by Hu5F9-G4 and Rituximab in Non-Hodgkin's Lymphoma. N Engl J Med. 2018 Nov 1;379(18):1711-1721. doi: 10.1056/NEJMoa1807315.
Results Reference
derived
Links:
URL
https://www.gileadclinicaltrials.com/study/?id=5F9003
Description
Gilead Clinical Trials Website

Learn more about this trial

Trial of Magrolimab (Hu5F9-G4) in Combination With Rituximab or Rituximab + Chemotherapy in Participants With Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma

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