Trial of Magrolimab (Hu5F9-G4) in Combination With Rituximab or Rituximab + Chemotherapy in Participants With Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma
- Conditions
- Non Hodgkin Lymphoma
- Interventions
- Registration Number
- NCT02953509
- Lead Sponsor
- Gilead Sciences
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 178
- 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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Magrolimab + Rituximab, Phase 1b Dose Escalation Magrolimab 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. Magrolimab + Rituximab, Phase 1b Dose Escalation Rituximab 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. Magrolimab + Rituximab, Phase 2 Indolent Lymphoma Magrolimab 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. Magrolimab + Rituximab, Phase 2 Indolent Lymphoma Rituximab 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. Magrolimab + R-GemOx, Phase 1b Dose Expansion Phase Magrolimab 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. Magrolimab + R-GemOx, Phase 1b Safety Dose Escalation Phase Gemcitabine 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. Magrolimab + Rituximab, Phase 2 Diffuse Large B-Cell lymphoma Rituximab 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. Magrolimab + R-GemOx, Phase 1b Safety Dose Escalation Phase Rituximab 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. Magrolimab + R-GemOx, Phase 1b Safety Dose Escalation Phase Oxaliplatin 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. Magrolimab + R-GemOx, Phase 1b Dose Expansion Phase Rituximab 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. Magrolimab + R-GemOx, Phase 1b Dose Expansion Phase Gemcitabine 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. Magrolimab + R-GemOx, Phase 1b Dose Expansion Phase Oxaliplatin 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. Magrolimab + Rituximab, Phase 2 Diffuse Large B-Cell lymphoma Magrolimab 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. Magrolimab + R-GemOx, Phase 1b Safety Dose Escalation Phase Magrolimab 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.
- Primary Outcome Measures
Name Time Method Phase 1b: Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs) Up to 28 days 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 First dose date up to 5 years Objective Response Rate as Defined by the Investigator According to the Lugano Classification for Lymphomas Up to 5 months Objective response is defined as complete response (CR) + partial response (PR) determined by Lugano classification for lymphomas.
- Secondary Outcome Measures
Name Time Method Progression Free Survival Up to 5 years Progression free survival is measured from dose initiation until the first date of objectively documented disease progression or death.
PK Parameter of Magrolimab: AUCtau 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 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: AUClast 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 AUClast is defined as the concentration of drug from time zero to the last observable concentration.
PK Parameter of Rituximab: AUClast 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 AUClast is defined as the concentration of drug from time zero to the last observable concentration.
PK Parameter of Rituximab: AUCtau 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 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 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 Cmax is defined as the maximum observed concentration of drug.
PK Parameter of Rituximab: Cmax 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 Cmax is defined as the maximum observed concentration of drug.
Percentage of Participants who Developed Anti-Magrolimab Antibodies 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 Duration of Response Up to 5 years 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.
Objective Rate of Response Defined by the Investigator According to the LYRIC Criteria for Lymphomas Up to 5 months Objective response is defined as complete response + partial response determined by Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) criteria.
Overall Survival Up to 5 years Overall Survival is measured from dose initiation until death.
Time to Progression First dose date up to 5 years Time to Progression is measured from dose initiation until the first date of objectively documented progressive disease criteria.
Trial Locations
- Locations (20)
Georgia Cancer Center at Augusta University
🇺🇸Augusta, Georgia, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Minnesota Medical Center, Fairview
🇺🇸Minneapolis, Minnesota, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
The Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Linear Clinical Research Ltd
🇦🇺Nedlands, Western Australia, Australia
The Churchill Hospital
🇬🇧Oxford, United Kingdom
Princess Alexandra Hospital
🇦🇺Brisbane, Queensland, Australia
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Stanford Cancer Center
🇺🇸Stanford, California, United States
National Institutes of Health Clinical Center/ National Cancer Institute
🇺🇸Bethesda, Maryland, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
St. Vincent's Hospital Melbourne
🇦🇺Melbourne, Victoria, Australia
Washington University School of Medicine Siteman Cancer Center
🇺🇸Saint Louis, Missouri, United States
University of Alabama At Birmingham (Uab)
🇺🇸Birmingham, Alabama, United States
City of Hope National Medical Center
🇺🇸Duarte, California, United States