UAB - Center for Clinical and Translational Science

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

Purpose

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 aspartate aminotransferase (ASCT) ineligible DLBCL participants.

Condition

Non Hodgkin Lymphoma

Eligibility

Eligible Ages: Over 18 Years
Eligible Genders: All
Accepts Healthy Volunteers: No

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

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.

Study Design

Phase: Phase 1/Phase 2
Study Type: Interventional
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Magrolimab + Rituximab, Phase 1b Dose Escalation	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.	Drug: Magrolimab Administered intravenously Other names: Hu5F9-G4 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 Other names: RITUXAN® MabThera
Experimental Magrolimab + Rituximab, Phase 2 Indolent Lymphoma	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.	Drug: Magrolimab Administered intravenously Other names: Hu5F9-G4 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 Other names: RITUXAN® MabThera
Experimental Magrolimab + Rituximab, Phase 2 Diffuse Large B-Cell lymphoma	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.	Drug: Magrolimab Administered intravenously Other names: Hu5F9-G4 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 Other names: RITUXAN® MabThera
Experimental Magrolimab + R-GemOx, Phase 1b Safety Dose Escalation Phase	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.	Drug: Magrolimab Administered intravenously Other names: Hu5F9-G4 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 Other names: RITUXAN® MabThera Drug: Gemcitabine Administered intravenously on Days 11, 23 for Cycle 1 and Days 2 and 15 for Cycles 2 to 4 Other names: Gemzar® Drug: Oxaliplatin Administered intravenously on Days 11, 23 for Cycle 1 and Days 2 and 15 for Cycles 2 to 4 Other names: Eloxatin®
Experimental Magrolimab + R-GemOx, Phase 1b Dose Expansion Phase	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.	Drug: Magrolimab Administered intravenously Other names: Hu5F9-G4 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 Other names: RITUXAN® MabThera Drug: Gemcitabine Administered intravenously on Days 11, 23 for Cycle 1 and Days 2 and 15 for Cycles 2 to 4 Other names: Gemzar® Drug: Oxaliplatin Administered intravenously on Days 11, 23 for Cycle 1 and Days 2 and 15 for Cycles 2 to 4 Other names: Eloxatin®

Recruiting Locations

University of Alabama At Birmingham (Uab) Comprehensive Cancer Center
Birmingham, Alabama 35294

More Details

Status: Recruiting
Sponsor: Gilead Sciences

Study Contact

Gilead Clinical Study Information Center
1-833-445-3230 (GILEAD-0)
GileadClinicalTrials@gilead.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.