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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02953509




Registration number
NCT02953509
Ethics application status
Date submitted
1/11/2016
Date registered
2/11/2016
Date last updated
23/05/2024

Titles & IDs
Public title
Trial of Magrolimab (Hu5F9-G4) in Combination With Rituximab or Rituximab + Chemotherapy in Participants With Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma
Scientific 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
Secondary ID [1] 0 0
2016-003408-29
Secondary ID [2] 0 0
5F9003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non Hodgkin Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Magrolimab
Treatment: Drugs - Rituximab
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Oxaliplatin

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.

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.

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.

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.

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.


Treatment: Drugs: Magrolimab
Administered intravenously

Treatment: Drugs: 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

Treatment: Drugs: Gemcitabine
Administered intravenously on Days 11, 23 for Cycle 1 and Days 2 and 15 for Cycles 2 to 4

Treatment: Drugs: Oxaliplatin
Administered intravenously on Days 11, 23 for Cycle 1 and Days 2 and 15 for Cycles 2 to 4
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1b: Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs)
Timepoint [1] 0 0
Up to 28 days
Primary outcome [2] 0 0
Percentage of Participants Experiencing Treatment Emergent Adverse Events
Timepoint [2] 0 0
First dose date up to 5 years
Primary outcome [3] 0 0
Objective Response Rate as Defined by the Investigator According to the Lugano Classification for Lymphomas
Timepoint [3] 0 0
Up to 5 months
Secondary outcome [1] 0 0
PK Parameter of Magrolimab: AUClast
Timepoint [1] 0 0
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 outcome [2] 0 0
PK Parameter of Rituximab: AUClast
Timepoint [2] 0 0
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 outcome [3] 0 0
PK Parameter of Magrolimab: AUCtau
Timepoint [3] 0 0
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 outcome [4] 0 0
PK Parameter of Rituximab: AUCtau
Timepoint [4] 0 0
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 outcome [5] 0 0
PK Parameter of Magrolimab: Cmax
Timepoint [5] 0 0
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 outcome [6] 0 0
PK Parameter of Rituximab: Cmax
Timepoint [6] 0 0
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 outcome [7] 0 0
Percentage of Participants who Developed Anti-Magrolimab Antibodies
Timepoint [7] 0 0
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 outcome [8] 0 0
Duration of Response
Timepoint [8] 0 0
Up to 5 years
Secondary outcome [9] 0 0
Progression Free Survival
Timepoint [9] 0 0
Up to 5 years
Secondary outcome [10] 0 0
Overall Survival
Timepoint [10] 0 0
Up to 5 years
Secondary outcome [11] 0 0
Time to Progression
Timepoint [11] 0 0
First dose date up to 5 years
Secondary outcome [12] 0 0
Objective Rate of Response Defined by the Investigator According to the LYRIC Criteria for Lymphomas
Timepoint [12] 0 0
Up to 5 months

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/11/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
25/03/2024
Sample size
Target
Accrual to date
Final
178
Recruitment in Australia
Recruitment state(s)
QLD,VIC,WA
Recruitment hospital [1] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [2] 0 0
St. Vincent's Hospital Melbourne - Melbourne
Recruitment hospital [3] 0 0
Linear Clinical Research Ltd - Nedlands
Recruitment postcode(s) [1] 0 0
4102 - Brisbane
Recruitment postcode(s) [2] 0 0
3065 - Melbourne
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Oklahoma
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United Kingdom
State/province [15] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Gilead Sciences
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
The Leukemia and Lymphoma Society
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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 autologous stem cell transplant (ASCT) ineligible DLBCL participants.
Trial website
https://clinicaltrials.gov/study/NCT02953509
Trial related presentations / publications
Advani R, Flinn I, Popplewell L, Forero A, Bartlett NL, Ghosh N, Kline J, Roschewski M, LaCasce A, Collins GP, Tran T, Lynn J, Chen JY, Volkmer JP, Agoram B, Huang J, Majeti R, Weissman IL, Takimoto CH, Chao MP, Smith SM. CD47 Blockade by Hu5F9-G4 and Rituximab in Non-Hodgkin's Lymphoma. N Engl J Med. 2018 Nov 1;379(18):1711-1721. doi: 10.1056/NEJMoa1807315.
Public notes

Contacts
Principal investigator
Name 0 0
Gilead Study Director
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02953509