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

NCT ID: NCT02953509

Last Updated: 2025-05-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 178 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-21
• Study Completion Date: 2024-03-25

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.

Conditions

Non Hodgkin Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1b Cohort 1: Magrolimab 10 mg/kg + Rituximab

Participants with B-cell non-hodgkin's lymphoma (NHL) will receive 1 mg/kg magrolimab intravenous (IV) infusion priming dose (over 3 hours) on Day 1 of Cycle 1, followed by weekly maintenance dose of 10 mg/kg magrolimab IV infusion (over 2 hours) on Days 8, 15, and 22 of Cycle 1 and Days 1, 8, 15, and 22 of Cycle 2 and beyond in combination with rituximab 375 mg/m\^2 IV infusion on Days 8, 15, and 22 of Cycle 1, followed by 1 dose on Day 1 of Cycles 2 to 6. Thereafter from Cycle 8 and beyond, rituximab will be administered on Day 1 of every other cycle (on even cycles). Each cycle length of 28 days.

Group Type: EXPERIMENTAL

Magrolimab

Intervention Type: DRUG

Administered intravenously

Rituximab

Intervention Type: DRUG

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

Phase 1b Cohort 2: Magrolimab 20 mg/kg + Rituximab

Participants with B-cell NHL will receive 1 mg/kg magrolimab IV infusion priming dose (over 3 hours) on Day 1 of Cycle 1, followed by weekly maintenance dose of 20 mg/kg magrolimab IV infusion (over 2 hours) on Days 8, 15, and 22 of Cycle 1 and Days 1, 8, 15, and 22 of Cycle 2 and beyond in combination with rituximab 375 mg/m\^2 IV infusion on Days 8, 15, and 22 of Cycle 1, followed by 1 dose on Day 1 of Cycles 2 to 6. Thereafter from Cycle 8 and beyond, rituximab will be administered on Day 1 of every other cycle (on even cycles). Each cycle length of 28 days.

Group Type: EXPERIMENTAL

Magrolimab

Intervention Type: DRUG

Administered intravenously

Rituximab

Intervention Type: DRUG

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

Phase 1b Cohort 3: Magrolimab 30 mg/kg + Rituximab

Participants with B-cell NHL will receive 1 mg/kg magrolimab IV infusion priming dose (over 3 hours) on Day 1 of Cycle 1, followed by weekly maintenance dose of 30 mg/kg magrolimab IV infusion (over 2 hours) on Days 8, 11,15, and 22 of Cycle 1 and Days 1, 8, 15, and 22 of Cycle 2 and beyond in combination with rituximab 375 mg/m\^2 IV infusion on Days 8, 15, and 22 of Cycle 1, followed by 1 dose on Day 1 of Cycles 2 to 6. Thereafter from Cycle 8 and beyond, rituximab will be administered on Day 1 of every other cycle (on even cycles). Each cycle length of 28 days.

Group Type: EXPERIMENTAL

Magrolimab

Intervention Type: DRUG

Administered intravenously

Rituximab

Intervention Type: DRUG

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

Phase 1b Cohort 4: Magrolimab 45 mg/kg + Rituximab

Participants with B-cell NHL will receive 1 mg/kg magrolimab IV infusion priming dose (over 3 hours) on Day 1 of Cycle 1, followed by weekly maintenance dose of 45 mg/kg magrolimab IV infusion (over 2 hours) on Days 8, 11, 15, and 22 of Cycle 1 and Days 1, 8, 15, and 22 of Cycle 2 and beyond in combination with rituximab 375 mg/m\^2 IV infusion on Days 8, 15, and 22 of Cycle 1, followed by 1 dose on Day 1 of Cycles 2 to 6. Thereafter from Cycle 8 and beyond, rituximab will be administered on Day 1 of every other cycle (on even cycles). Each cycle length of 28 days.

Group Type: EXPERIMENTAL

Magrolimab

Intervention Type: DRUG

Administered intravenously

Rituximab

Intervention Type: DRUG

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

Phase 1b Cohort 5: Magrolimab 30 mg/kg + Rituximab + Gemcitabine + Oxaliplatin

Autologous stem cell transplant ineligible diffuse large B-cell lymphoma (DLBCL) participants will receive 1 mg/kg magrolimab IV infusion priming dose(over 3 hours)on Day 1 of Cycle 1,followed by maintenance dose of 30 mg/kg on Days 8, 11, 15, 22, and 29 of Cycle 1;Days 1, 8, 15, and 22 of Cycle 2 followed by Days 1 and 15 of subsequent cycles.Cycle length will be 28 days.Rituximab 375 mg/m\^2 IV infusion will be given on Days 8, 15, 22, and 29 of Cycle 1,followed by 1 dose on Day 1 of Cycles 2 to 6.Thereafter from Cycle 8 and beyond,rituximab will be administered on Day 1 of every other cycle(on even cycles).Gemcitabine 1000 mg/m\^2 and oxaliplatin 100 mg/m\^2 IV infusion will be given as on Days 11 and 23 of Cycle 1 and Days 2 and 15 of Cycles 2 to 4.Granulocyte colony stimulating factor (G-CSF) prophylaxis will be given with gemcitabine and oxaliplatin treatment(Cycles 1-4).Allopurinol 300 mg orally daily will be administered for the first cycle only.

Group Type: EXPERIMENTAL

Magrolimab

Intervention Type: DRUG

Administered intravenously

Rituximab

Intervention Type: DRUG

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

Gemcitabine

Intervention Type: DRUG

Administered intravenously on Days 11, 23 for Cycle 1 and Days 2 and 15 for Cycles 2 to 4

Oxaliplatin

Intervention Type: DRUG

Administered intravenously on Days 11, 23 for Cycle 1 and Days 2 and 15 for Cycles 2 to 4

Allopurinol

Intervention Type: DRUG

Administered orally during Cycle 1

Phase 1b Cohort 6: Magrolimab 45 mg/kg + Rituximab + Gemcitabine + Oxaliplatin

Autologous stem cell transplant ineligible DLBCL participants will receive 1 mg/kg magrolimab IV infusion priming dose (over 3 hours) on Day 1 of Cycle 1, followed by maintenance dose of 45 mg/kg on Days 8, 11, 15, 22, and 29 of Cycle 1; Days 1, 8, 15, and 22 of Cycle 2 followed by Days 1 and 15 of subsequent cycles. The cycle length of 28 days. Rituximab 375 mg/m\^2 IV infusion will be administered on Days 8, 15, 22, and 29 of Cycle 1, followed by 1 dose on Day 1 for Cycles 2 to 6. Thereafter from Cycle 8 and beyond, rituximab will be administered on Day 1 of every other cycle (on even cycles). Gemcitabine 1000 mg/m\^2 and oxaliplatin 100 mg/m\^2 IV infusion will be administered as on Days 11 and 23 of Cycle 1 and Days 2 and 15 of Cycles 2 to 4. G-CSF prophylaxis will be administered with gemcitabine and oxaliplatin treatment (Cycles 1-4). Allopurinol 300 mg orally daily will be administered for the first cycle only.

Group Type: EXPERIMENTAL

Magrolimab

Intervention Type: DRUG

Administered intravenously

Rituximab

Intervention Type: DRUG

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

Gemcitabine

Intervention Type: DRUG

Administered intravenously on Days 11, 23 for Cycle 1 and Days 2 and 15 for Cycles 2 to 4

Oxaliplatin

Intervention Type: DRUG

Administered intravenously on Days 11, 23 for Cycle 1 and Days 2 and 15 for Cycles 2 to 4

Allopurinol

Intervention Type: DRUG

Administered orally during Cycle 1

Phase 2 Cohort 1: Magrolimab 30 mg/kg + Rituximab

Participants with B-cell indolent NHL (iNHL) (including follicular lymphoma \[FL\] and marginal zone lymphoma \[MZL\]) and DLBCL will receive 1 mg/kg magrolimab IV infusion priming dose (over 3 hours) on Day 1 of Cycle 1, followed by weekly maintenance dose of 30 mg/kg magrolimab IV infusion (over 2 hours) on Days 8, 15, and 22 of Cycle 1, and Days 1 and 15 of subsequent cycles in combination with rituximab 375 mg/m\^2 IV infusion on Days 8, 15, and 22 of Cycle 1, followed by 1 dose on Day 1 of Cycles 2 to 6. Thereafter from Cycle 8 and beyond, rituximab will be administered on Day 1 of every other cycle (on even cycles). Each cycle length of 28 days.

Group Type: EXPERIMENTAL

Magrolimab

Intervention Type: DRUG

Administered intravenously

Rituximab

Intervention Type: DRUG

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

Phase 2 Cohort 2: Magrolimab 30 mg/kg + Rituximab

Participants with B-cell iNHL (including FL and MZL) and DLBCL will receive 1 mg/kg magrolimab IV infusion priming dose (over 3 hours) on Day 1 of Cycle 1, followed by weekly maintenance dose of 30 mg/kg magrolimab IV infusion (over 2 hours) on Days 8, 11, 15, and 22 of Cycle 1; Days 1, 8, 15, and 22 of Cycle 2 and Days 1 and 15 of subsequent cycles in combination with rituximab 375 mg/m\^2 IV infusion on Days 8, 15, and 22 of Cycle 1, followed by 1 dose on Day 1 for Cycles 2 to 6. Thereafter from Cycle 8 and beyond, rituximab will be administered on Day 1 of every other cycle (on even cycles). Each cycle length of 28 days.

Group Type: EXPERIMENTAL

Magrolimab

Intervention Type: DRUG

Administered intravenously

Rituximab

Intervention Type: DRUG

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

Phase 2 Cohort 3: Magrolimab 45 mg/kg + Rituximab

Participants with B-cell iNHL (including FL and MZL) and DLBCL will receive 1 mg/kg magrolimab IV infusion priming dose (over 3 hours) on Day 1 of Cycle 1, followed by weekly maintenance dose of 45 mg/kg magrolimab IV infusion (over 2 hours) on Days 8, 11, 15, and 22 of Cycle 1; Days 1, 8, 15, and 22 of Cycle 2 and Days 1 and 15 of subsequent cycles in combination with rituximab 375 mg/m\^2 IV infusion on Days 8, 15, and 22 of Cycle 1, followed by 1 dose on Day 1 for Cycles 2 to 6. Thereafter from Cycle 8 and beyond, rituximab will be administered on Day 1 of every other cycle (on even cycles). Each cycle length of 28 days.

Group Type: EXPERIMENTAL

Magrolimab

Intervention Type: DRUG

Administered intravenously

Rituximab

Intervention Type: DRUG

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

Phase 2 Cohort 4: Magrolimab 30 mg/kg + Rituximab

Participants with DLBCL will receive 1 mg/kg magrolimab IV infusion priming dose (over 3 hours) on Day 1 of Cycle 1, followed by weekly maintenance dose of 30 mg/kg magrolimab IV infusion (over 2 hours) on Days 8, 15, and 22 of Cycle 1; Days 1, 8, 15, and 22 of Cycle 2 and Days 1 and 15 of subsequent cycles in combination with rituximab 375 mg/m\^2 IV infusion on Days 8, 15, and 22 of Cycle 1, followed by 1 dose on Day 1 for Cycles 2 to 6. Thereafter from Cycle 8 and beyond, rituximab will be administered on Day 1 of every other cycle (on even cycles). Each Cycle length of 28 days.

Group Type: EXPERIMENTAL

Magrolimab

Intervention Type: DRUG

Administered intravenously

Rituximab

Intervention Type: DRUG

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

Interventions

Magrolimab

Administered intravenously

Intervention Type: DRUG

Rituximab

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

Gemcitabine

Administered intravenously on Days 11, 23 for Cycle 1 and Days 2 and 15 for Cycles 2 to 4

Intervention Type: DRUG

Oxaliplatin

Administered intravenously on Days 11, 23 for Cycle 1 and Days 2 and 15 for Cycles 2 to 4

Intervention Type: DRUG

Allopurinol

Administered orally during Cycle 1

Intervention Type: DRUG

Other Intervention Names

Hu5F9-G4; RITUXAN®; MabThera; Gemzar®; Eloxatin®

Eligibility Criteria

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 cluster of differentiation (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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Leukemia and Lymphoma Society

OTHER

Sponsor Role: collaborator

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

University of Alabama At Birmingham (Uab)

Birmingham, Alabama, United States

City of Hope National Medical Center

Duarte, California, United States

Stanford Cancer Center

Stanford, California, United States

Georgia Cancer Center at Augusta University

Augusta, Georgia, United States

University of Chicago Medical Center

Chicago, Illinois, United States

National Institutes of Health Clinical Center/ National Cancer Institute

Bethesda, Maryland, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

University of Minnesota Medical Center, Fairview

Minneapolis, Minnesota, United States

Washington University School of Medicine Siteman Cancer Center

St Louis, Missouri, United States

Levine Cancer Institute

Charlotte, North Carolina, United States

Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

The Sarah Cannon Research Institute

Nashville, Tennessee, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Princess Alexandra Hospital

Brisbane, Queensland, Australia

St. Vincent's Hospital Melbourne

Melbourne, Victoria, Australia

Linear Clinical Research Ltd

Nedlands, Western Australia, Australia

The Churchill Hospital

Oxford, , United Kingdom

Countries

United States; Australia; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 30380386 (View on PubMed)

Advani R, Volkmer JP, Chao MP. CD47 Blockade and Rituximab in Non-Hodgkin's Lymphoma. N Engl J Med. 2019 Jan 31;380(5):497-498. doi: 10.1056/NEJMc1816156. No abstract available.

Reference Type: BACKGROUND

PMID: 30699313 (View on PubMed)

Mehta A, Popplewell L, Collins GP, Smith S, Flinn I, Bartlett NL, et al. Magrolimab in Combination With Rituximab in Patients With Relapsed or Refractory Indolent Non-Hodgkin Lymphoma: 3-Year Follow-up Results From a Phase 1/2 Trial. Am J Hematol 2022;97:S3-S40.

Reference Type: BACKGROUND

Maakaron J, Asch AS, Popplewell LL, Collins GP, Flinn IW, Ghosh N, et al. Magrolimab in Combination with Rituximab + Chemotherapy in Patients with Relapsed or Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL). Blood 2022;140 (Supplement 1):3728-3730.

Reference Type: BACKGROUND

Advani R, Bartlett NL, Smith SM, Roschewski M, Popplewell L, Flinn I, et al. Activity of thefirst-in-class anti-CD47 antibody Hu5F9-G4 with rituximab in relapsed/refractory Non-Hodgkin's lymphoma: interim Phase 1b/2 results [Presentation]. 15th International Conference on Malignant Lymphoma (ICML); 2019 18-22 June; Lugano, Switzerland.

Reference Type: BACKGROUND

Advani R, Bartlett NL, Smith SM, Roschewski M, Popplewell L, Flinn I, et al. The first-in-class anti-CD47 antibody Hu5F9-G4 + rituximab induces durable responses in relapsed/refractory DLBCL and indolent lymphoma: Interim Phase 1b/2 results [Abstract]. 15th International Conference on Malignant Lymphoma (ICML); 2019 18-22 June; Lugano, Switzerland.

Reference Type: BACKGROUND

Roschewski M, Advani R, Bartlett NL, Smith SM, Popplewell L, Flinn I, et al. Activity of the first-in-class anti-CD47 antibody Hu5F9-G4 with rituximab in relapsed/refractory Non-Hodgkin's lymphoma: interim Phase 1b/2 results [Presentation]. 24th Congress of the European Hematology Association (EHA); 2019 13-16 June; Amsterdam, Netherlands.

Reference Type: BACKGROUND

Advani R, Bartlett NL, Smith SM, Roschewski M, Popplewell L, Flinn I, et al. The first-in-class anti-CD47 antibody Hu5F9-G4 with rituximab induces durable responses in relapsed/refractory DLBCL and indolent lymphoma: Interim Phase 1b/2 results [Abstract]. 24th Congress of the European Hematology Association (EHA); 2019 13-16 June; Amsterdam, Netherlands.

Reference Type: BACKGROUND

Wang B, Jin D, Cho MM, Takimoto C, Chao M, Agoram B. Magrolimab (Hu5F9-G4, 5F9) Treatment Does Not Alter Rituximab Pharmacokinetics in Patients With Non-Hodgkin's Lymphoma [Poster THU-008]. Eleventh American Conference on Pharmacometrics (ACoP11) Virtual; 2020 09-13 November.

Reference Type: BACKGROUND

Wang B, Jin D, Takimoto C, Chao M, Agoram B. Magrolimab Treatment Does Not Alter Rituximab Pharmacokinetics in Patients with Non-Hodgkin's Lymphoma [Abstract]. Eleventh American Conference on Pharmacometrics (ACoP11) Virtual; 2020 09-13 November.

Reference Type: BACKGROUND

Jin DCY, Wang B, Sikic B, Advani R, Chao M, Takimoto C, et al. Population-Pharmacokinetics of Magrolimab (Hu5F9-G4, 5F9) in Patients With Solid Tumors and Lymphomas [Poster TUE-020]. Eleventh American Conference on Pharmacometrics (ACoP11) Virtual; 2020 09-13 November.

Reference Type: BACKGROUND

Jin DCY, Wang B, Sikic B, Advani R, Chao M, Takimoto C, et al. Population pharmacokinetics of magrolimab (5F9, Hu5F9-G4) in patients with solid tumors and lymphomas [Abstract]. Eleventh American Conference on Pharmacometrics (ACoP11) Virtual; 2020 09-13 November.

Reference Type: BACKGROUND

Maakaron JE, Asch A, Popplewell L, Collins GP, Flinn IW, Ghosh N, Keane C, Ku M, Mehta A, Roschewski M, Hacohen-Kleiman G, Huo Y, Zhang Y, Renard C, Smith SM, Advani R. Magrolimab plus rituximab with or without chemotherapy in patients with relapsed/refractory diffuse large B-cell lymphoma. Blood Adv. 2024 Nov 26;8(22):5864-5874. doi: 10.1182/bloodadvances.2024013338.

Reference Type: DERIVED

PMID: 39293083 (View on PubMed)

Mehta A, Popplewell L, Collins GP, Smith SM, Flinn IW, Bartlett NL, Ghosh N, Hacohen-Kleiman G, Huo Y, Su-Feher L, Renard C, Advani R, Roschewski M. Magrolimab plus rituximab in relapsed/refractory indolent non-Hodgkin lymphoma: 3-year follow-up of a phase 1/2 trial. Blood Adv. 2024 Nov 26;8(22):5855-5863. doi: 10.1182/bloodadvances.2024013277.

Reference Type: DERIVED

PMID: 39213421 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.gileadclinicaltrials.com/study/?id=5F9003

Gilead Clinical Trials Website

Other Identifiers

2016-003408-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

5F9003

Identifier Type: -

Identifier Source: org_study_id