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

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ClinicalTrials.gov Identifier: NCT02953509
Recruitment Status : Recruiting
First Posted : November 2, 2016
Last Update Posted : September 24, 2021
Sponsor:
Collaborator:
The Leukemia and Lymphoma Society
Information provided by (Responsible Party):
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 aspartate aminotransferase (ASCT) ineligible DLBCL participants.

Condition or disease Intervention/treatment Phase
Non Hodgkin Lymphoma Drug: Magrolimab Drug: Rituximab Drug: Gemcitabine Drug: Oxaliplatin Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 422 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 21, 2016
Estimated Primary Completion Date : November 2021
Estimated Study Completion Date : August 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Rituximab

Arm Intervention/treatment
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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Gemzar®

Drug: Oxaliplatin
Administered intravenously on Days 11, 23 for Cycle 1 and Days 2 and 15 for Cycles 2 to 4
Other Name: 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 Name: 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 Name: Gemzar®

Drug: Oxaliplatin
Administered intravenously on Days 11, 23 for Cycle 1 and Days 2 and 15 for Cycles 2 to 4
Other Name: Eloxatin®




Primary Outcome Measures :
  1. Phase 1b: Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs) [ Time Frame: 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.

  2. Percentage of Participants Experiencing Treatment Emergent Adverse Events [ Time Frame: First dose date up to 5 years ]
  3. Objective Response Rate as Defined by the Investigator According to the Lugano Classification for Lymphomas [ Time Frame: Up to 5 months ]
    Objective response is defined as complete response (CR) + partial response (PR) determined by Lugano classification for lymphomas.


Secondary Outcome Measures :
  1. 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 ]
    AUClast is defined as the concentration of drug from time zero to the last observable concentration.

  2. 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 ]
    AUClast is defined as the concentration of drug from time zero to the last observable concentration.

  3. 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 ]
    AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

  4. 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 ]
    AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

  5. 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 ]
    Cmax is defined as the maximum observed concentration of drug.

  6. 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 ]
    Cmax is defined as the maximum observed concentration of drug.

  7. 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 ]
  8. Duration of Response [ Time Frame: 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.

  9. Progression Free Survival [ Time Frame: Up to 5 years ]
    Progression free survival is measured from dose initiation until the first date of objectively documented disease progression or death.

  10. Overall Survival [ Time Frame: Up to 5 years ]
    Overall Survival is measured from dose initiation until death.

  11. Time to Progression [ Time Frame: 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.

  12. Objective Rate of Response Defined by the Investigator According to the LYRIC Criteria for Lymphomas [ Time Frame: Up to 5 months ]
    Objective response is defined as complete response + partial response determined by Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) criteria.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02953509


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

Locations
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Sponsors and Collaborators
Gilead Sciences
The Leukemia and Lymphoma Society
Investigators
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Study Director: Gilead Study Director Gilead Sciences
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02953509    
Other Study ID Numbers: 5F9003
2016-003408-29 ( EudraCT Number )
First Posted: November 2, 2016    Key Record Dates
Last Update Posted: September 24, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Gemcitabine
Rituximab
Magrolimab
Oxaliplatin
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents