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

Non Hodgkin Lymphoma Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT02953509
• Other study ID #: 5F9003
• Secondary ID: 2016-003408-29
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: November 21, 2016
• Est. completion date: March 25, 2024

Study information

• Verified date: May 2024
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 178
• Est. completion date: March 25, 2024
• Est. primary completion date: March 25, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (SIRPa) 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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin
• Non Hodgkin Lymphoma

Intervention

Drug:
• Magrolimab
Administered intravenously
• 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
• Gemcitabine
Administered intravenously on Days 11, 23 for Cycle 1 and Days 2 and 15 for Cycles 2 to 4
• Oxaliplatin
Administered intravenously on Days 11, 23 for Cycle 1 and Days 2 and 15 for Cycles 2 to 4

Locations

Country	Name	City	State
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Australia	St. Vincent's Hospital Melbourne	Melbourne	Victoria
Australia	Linear Clinical Research Ltd	Nedlands	Western Australia
United Kingdom	The Churchill Hospital	Oxford
United States	University of Michigan	Ann Arbor	Michigan
United States	Georgia Cancer Center at Augusta University	Augusta	Georgia
United States	National Institutes of Health Clinical Center/ National Cancer Institute	Bethesda	Maryland
United States	University of Alabama At Birmingham (Uab)	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	University of Chicago Medical Center	Chicago	Illinois
United States	City of Hope National Medical Center	Duarte	California
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of Minnesota Medical Center, Fairview	Minneapolis	Minnesota
United States	The Sarah Cannon Research Institute	Nashville	Tennessee
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Washington University School of Medicine Siteman Cancer Center	Saint Louis	Missouri
United States	Stanford Cancer Center	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Gilead Sciences	The Leukemia and Lymphoma Society

Countries where clinical trial is conducted

United States,  Australia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1b: Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs)	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.	Up to 28 days
Primary	Percentage of Participants Experiencing Treatment Emergent Adverse Events		First dose date up to 5 years
Primary	Objective Response Rate as Defined by the Investigator According to the Lugano Classification for Lymphomas	Objective response is defined as complete response (CR) + partial response (PR) determined by Lugano classification for lymphomas.	Up to 5 months
Secondary	PK Parameter of Magrolimab: AUClast	AUClast is defined as the concentration of drug from time zero to the last observable concentration.	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
Secondary	PK Parameter of Rituximab: AUClast	AUClast is defined as the concentration of drug from time zero to the last observable concentration.	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
Secondary	PK Parameter of Magrolimab: AUCtau	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).	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
Secondary	PK Parameter of Rituximab: AUCtau	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).	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
Secondary	PK Parameter of Magrolimab: Cmax	Cmax is defined as the maximum observed concentration of drug.	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
Secondary	PK Parameter of Rituximab: Cmax	Cmax is defined as the maximum observed concentration of drug.	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
Secondary	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
Secondary	Duration of Response	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.	Up to 5 years
Secondary	Progression Free Survival	Progression free survival is measured from dose initiation until the first date of objectively documented disease progression or death.	Up to 5 years
Secondary	Overall Survival	Overall Survival is measured from dose initiation until death.	Up to 5 years
Secondary	Time to Progression	Time to Progression is measured from dose initiation until the first date of objectively documented progressive disease criteria.	First dose date up to 5 years
Secondary	Objective Rate of Response Defined by the Investigator According to the LYRIC Criteria for Lymphomas	Objective response is defined as complete response + partial response determined by Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) criteria.	Up to 5 months

External Links

•   Gilead Clinical Trials Website