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

Sponsor

Gilead Sciences (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02953509

Collaborator

The Leukemia and Lymphoma Society (Other)

178

Enrollment

Locations

Arms

116.3

Anticipated Duration (Months)

8.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Study Design

Study Type:

Interventional

Actual Enrollment :

178 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 :

Nov 21, 2016

Actual Primary Completion Date :

Nov 21, 2021

Anticipated Study Completion Date :

Aug 1, 2026

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

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 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 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.
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.
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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama At Birmingham (Uab)	Birmingham	Alabama	United States	35924
2	City of Hope National Medical Center	Duarte	California	United States	91010
3	Stanford Cancer Center	Stanford	California	United States	94305
4	Georgia Cancer Center at Augusta University	Augusta	Georgia	United States	30912
5	University of Chicago Medical Center	Chicago	Illinois	United States	60637
6	National Institutes of Health Clinical Center/ National Cancer Institute	Bethesda	Maryland	United States	20892
7	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
8	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
9	University of Michigan	Ann Arbor	Michigan	United States	48109
10	University of Minnesota Medical Center, Fairview	Minneapolis	Minnesota	United States	55455
11	Washington University School of Medicine Siteman Cancer Center	Saint Louis	Missouri	United States	63110
12	Levine Cancer Institute	Charlotte	North Carolina	United States	28204
13	Stephenson Cancer Center	Oklahoma City	Oklahoma	United States	73104
14	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
15	The Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
16	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
17	Princess Alexandra Hospital	Brisbane	Queensland	Australia	4102
18	St. Vincent's Hospital Melbourne	Melbourne	Victoria	Australia	3065
19	Linear Clinical Research Ltd	Nedlands	Western Australia	Australia	6009
20	The Churchill Hospital	Oxford		United Kingdom	OX3 7LE