Clinical Trials /

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

NCT02953509

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.

Related Conditions:
  • B-Cell Non-Hodgkin Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
  • Marginal Zone Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Trial of Hu5F9-G4 in Combination With Rituximab in 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
  • NCT ID: NCT02953509

Conditions

  • Lymphoma, Non-Hodgkin
  • Lymphoma, Large B-Cell, Diffuse
  • Indolent Lymphoma

Interventions

DrugSynonymsArms
Hu5F9-G4magrolimabPhase 1b diffuse large B-cell lymphoma
RituximabRITUXAN®, MabTheraPhase 1b diffuse large B-cell lymphoma
Gemcitabine HydrochlorideGemzarPhase 1b diffuse large B-cell lymphoma
OxaliplatinEloxatinPhase 1b diffuse large B-cell lymphoma

Purpose

This Phase 1b/2 trial will evaluate Hu5F9-G4 (magrolimab) in combination with rituximab and magrolimab or in combination with R-GemOx. Magrolimab is a monoclonal antibody which is designed to block a protein called CD47, which is widely expressed on human cancer cells. Blocking CD47 with magrolimab may enable the body's immune system to find and destroy the cancer cells. Rituximab is a monoclonal antibody drug that is used for treatment of non-Hodgkin's lymphoma and other types of cancer. Gemcitabine and Oxaliplatin are chemotherapy commonly used with rituximab in treating NHL. The major aims of the trial are: (Phase 1b) to investigate the safety and tolerability of sequential dose cohorts and to determine a recommended Phase 2 dose for Hu5F9-G4 in combination with rituximab, and (Phase 2) to evaluate the efficacy of Hu5F9-G4 in combination with rituximab in patients with indolent lymphoma or diffuse large B-cell lymphoma as measured by the overall response rate.

Trial Arms

NameTypeDescriptionInterventions
Phase 1b dose escalationExperimentalIn Phase 1b, patients with B-cell non-Hodgkin's lymphoma will receive escalating doses of Hu5F9-G4 in combination with ritixumab.
  • Hu5F9-G4
  • Rituximab
Phase 2 indolent lymphomaExperimentalIn Phase 2, patients with indolent lymphoma will receive Hu5F9-G4 in combination with ritixumab.
  • Hu5F9-G4
  • Rituximab
Phase 2 diffuse large B-cell lymphomaExperimentalIn Phase 2, patients with diffuse large B-cell lymphoma will receive Hu5F9-G4 in combination with ritixumab.
  • Hu5F9-G4
  • Rituximab
Phase 1b diffuse large B-cell lymphomaExperimentalIn Phase 1b, patients with diffuse large B-cell lymphoma will receive escalating doses of magrolimab in combination with ritixumab + gemcitabine and oxaliplatin.
  • Hu5F9-G4
  • Rituximab
  • Gemcitabine Hydrochloride
  • Oxaliplatin

Eligibility Criteria

        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 CAR-T therapy
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose-limiting toxicities (Number of participants with a DLT)
Time Frame:28 days
Safety Issue:
Description:Dose-limiting toxicities (DLTs) (Phase 1b only) Number of participants with a DLT

Secondary Outcome Measures

Measure:PK profile
Time Frame:up to 52 weeks
Safety Issue:
Description:Concentration vs time of magrolimab in combination with rituximab or rituximab +GemOx
Measure:ADA to magrolimab
Time Frame:up to 52 weeks
Safety Issue:
Description:Presence or absence of antibodies
Measure:Duration of response; Progression Free Survival, Overall Survival, Time to Progression
Time Frame:up to 40 months
Safety Issue:
Description:Response data over time as defined by the investigator according to Lugano and LYRIC criteria
Measure:Objective Rate of Response
Time Frame:8 weeks
Safety Issue:
Description:Assessed Investigator according to LYRIC criteria for lymphomas

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Forty Seven, Inc.

Trial Keywords

  • non-Hodgkin's lymphoma
  • diffuse large B-cell lymphoma
  • indolent lymphoma
  • Hu5F9-G4
  • CD47
  • magrolimab

Last Updated

February 21, 2020