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 autologous stem cell transplant (ASCT) ineligible DLBCL participants.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
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 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 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

ArmDescriptionAssigned Intervention
Experimental
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.
  • 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
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.
  • 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
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.
  • 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
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.
  • 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
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.
  • 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®
  • Drug: Allopurinol
    Administered orally during Cycle 1
Experimental
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.
  • 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®
  • Drug: Allopurinol
    Administered orally during Cycle 1
Experimental
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.
  • 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
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.
  • 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
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.
  • 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
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.
  • 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

More Details

Status
Terminated
Sponsor
Gilead Sciences

Study Contact

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.