Description:
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.
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
5F9003
- SECONDARY ID:
2016-003408-29
- NCT ID:
NCT02953509
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Magrolimab | Hu5F9-G4 | Magrolimab + R-GemOx, Phase 1b Dose Expansion Phase |
| Rituximab | RITUXAN®, MabThera | Magrolimab + R-GemOx, Phase 1b Dose Expansion Phase |
| Gemcitabine | Gemzar® | Magrolimab + R-GemOx, Phase 1b Dose Expansion Phase |
| Oxaliplatin | Eloxatin® | Magrolimab + R-GemOx, Phase 1b Dose Expansion Phase |
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Magrolimab + Rituximab, Phase 1b Dose Escalation | Experimental | 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 | Experimental | 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 Diffuse Large B-Cell lymphoma | Experimental | 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 | Experimental | 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
- Gemcitabine
- Oxaliplatin
|
| Magrolimab + R-GemOx, Phase 1b Dose Expansion Phase | Experimental | 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
- Gemcitabine
- Oxaliplatin
|
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Phase 1b: Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs) |
| Time Frame: | Up to 28 days |
| Safety Issue: | |
| 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. |
Secondary Outcome Measures
| Measure: | PK Parameter of Magrolimab: AUClast |
| 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 |
| Safety Issue: | |
| Description: | AUClast is defined as the concentration of drug from time zero to the last observable concentration. |
| Measure: | PK Parameter of Rituximab: AUClast |
| 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 |
| Safety Issue: | |
| Description: | AUClast is defined as the concentration of drug from time zero to the last observable concentration. |
| Measure: | PK Parameter of Magrolimab: AUCtau |
| 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 |
| Safety Issue: | |
| Description: | AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). |
| Measure: | PK Parameter of Rituximab: AUCtau |
| 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 |
| Safety Issue: | |
| Description: | AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). |
| Measure: | PK Parameter of Magrolimab: Cmax |
| 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 |
| Safety Issue: | |
| Description: | Cmax is defined as the maximum observed concentration of drug. |
| Measure: | PK Parameter of Rituximab: Cmax |
| 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 |
| Safety Issue: | |
| Description: | Cmax is defined as the maximum observed concentration of drug. |
| Measure: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | Duration of Response |
| Time Frame: | Up to 5 years |
| Safety Issue: | |
| 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. |
| Measure: | Progression Free Survival |
| Time Frame: | Up to 5 years |
| Safety Issue: | |
| Description: | Progression free survival is measured from dose initiation until the first date of objectively documented disease progression or death. |
| Measure: | Overall Survival |
| Time Frame: | Up to 5 years |
| Safety Issue: | |
| Description: | Overall Survival is measured from dose initiation until death. |
| Measure: | Time to Progression |
| Time Frame: | First dose date up to 5 years |
| Safety Issue: | |
| Description: | Time to Progression is measured from dose initiation until the first date of objectively documented progressive disease criteria. |
| Measure: | Objective Rate of Response Defined by the Investigator According to the LYRIC Criteria for Lymphomas |
| Time Frame: | Up to 5 months |
| Safety Issue: | |
| Description: | Objective response is defined as complete response + partial response determined by Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) criteria. |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Gilead Sciences |
Last Updated
August 24, 2021
