This phase Ib/II trial identifies the best dose and possible benefits and/or side effects of magrolimab when given in combination with mogamulizumab in treating patients with stage IB-IV mycosis fungoides or Sezary syndrome types of T-cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Magrolimab and mogamulizumab are monoclonal antibodies that may interfere with the ability of cancer cells to grow and spread. Treatment with magrolimab in combination with mogamulizumab may stabilize cancer for longer period than the usual treatment in patients with relapsed/refractory T-cell lymphoma who have been previously treated.
PRIMARY OBJECTIVES: I. To characterize the safety and toxicity profile and to determine a safe recommended phase 2 dose (RP2D) of Hu5F9-G4 (magrolimab) when given in combination with mogamulizumab. (Phase I) II. To compare the proportion of patients who achieve a partial or complete response lasting at least 6 months (ORR6) of the combination of Hu5F9-G4 (magrolimab) and mogamulizumab versus mogamulizumab alone. (Phase II) SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. (Phase I) II. To compare the efficacy of the combination of Hu5F9-G4 (magrolimab) and mogamulizumab versus mogamulizumab alone with respect to the following endpoints (Phase II): IIa. Overall response rate (ORR); overall response rate lasting at least 4 months (ORR4); overall response rate lasting at least 12 months (ORR12). IIb. Duration of response (DOR). IIc. Progression-free survival (PFS). IId. Time to next treatment (TTNT). EXPLORATORY OBJECTIVES: I. To identify potential biomarkers that correlate with response to mogamulizumab and Hu5F9-G4 (magrolimab) including (Phase I and II): Ia. Expression of CCR4. Ib. Somatic mutations and germline polymorphisms. Ic. Phenotyping of lymphoma and immune microenvironment. Id. Functional assay of phagocytosis. OUTLINE: This is a phase Ib, dose de-escalation study of magrolimab followed by a phase II study. Patients in the phase Ib study receive treatment as in Arm I. Patients in the phase II study are randomized to Arm I or Arm II. ARM I: Patients receive magrolimab intravenously (IV) over 2-3 hours weekly during cycles 1-2, then every 2 weeks (Q2W) during cycles 3-12. Patients also receive mogamulizumab IV over at least 60 minutes weekly during cycle 1, then Q2W during cycles 2-12. Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo positron emission tomography (PET)/computed tomography (CT) or diagnostic CT, blood sample collection, and may undergo a skin punch biopsy during screening and on study. ARM II: Patients receive mogamulizumab IV over at least 60 minutes weekly during cycle 1, then Q2W during cycles 2-12. Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients who have received at least 2 full treatment cycles and have progressive disease (PD) or have received at least 6 full treatment cycles and have stable disease (SD) may crossover to Arm I. Patients undergo PET/CT or diagnostic CT, blood sample collection, and may undergo a skin punch biopsy during screening and on study. After completion of study treatment, patients are followed up every 3 months for 2 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
8
Undergo blood sample collection
Undergo PET/CT or diagnostic CT
Given IV
Given IV
Undergo PET/CT
Undergo skin punch biopsy
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Los Angeles General Medical Center
Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
Stanford Cancer Institute Palo Alto
Palo Alto, California, United States
Northwestern University
Chicago, Illinois, United States
Washington University School of Medicine
St Louis, Missouri, United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey, United States
Memorial Sloan Kettering Commack
Commack, New York, United States
...and 8 more locations
Recommended Phase 2 Dose (RP2D) of Magrolimab When Given in Combination With Mogamulizumab (Phase Ib)
The phase 1b portion of the trial was designed to determine a RP2D of Hu5F9-G4 (magrolimab) and was planned to enroll 6-18 patients.
Time frame: Up to 4 weeks from the first infusion of magrolimab (priming infusion)
Overall Response Rate at 6 Months (ORR6) (Phase II)
Will be defined as the proportion of patients who have a partial or complete response to therapy AND a duration of response \>= 6 months. Will use a stratified Cochran-Mantel-Haenszel chi-squared test to compare between-group differences in ORR6 proportion. Will also conduct a secondary analysis on the intent-to-treat population (all patients randomized to a therapy and assigned a study number) and an efficacy evaluable set (all patients who received the first 12 weeks of treatment and completed the week 12 response assessment).
Time frame: At 6 months
Overall Response Rate (ORR) (Phase Ib)
Defined as the proportion of patients who have a partial or complete response to therapy as defined by the global response score.
Time frame: Up to 2 years
Overall Response Rate at 4 Months (ORR4) (Phase II)
Will be defined as the proportion of patients who have a partial or complete response to therapy AND a duration of response \>= 4 months. Will be assessed by the chi-squared method.
Time frame: At 4 months
Overall Response Rate at 12 Months (ORR12) (Phase II)
Will be defined as the proportion of patients who have a partial or complete response to therapy AND a duration of response \>= 12 months. Will be assessed by the chi-squared method.
Time frame: At 12 months
Progression-free Survival (PFS) (Phase II)
Will be assessed by the Kaplan-Meier method and the log-rank test.
Time frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 2 years
Duration of Response (DOR) (Phase II)
Will be assessed by the Kaplan-Meier method and the log-rank test.
Time frame: From the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrence or progressive disease is objectively documented, assessed up to 2 years
Time to Next Treatment (TTNT) (Phase II)
Will be assessed by the Kaplan-Meier method and the log-rank test.
Time frame: From the start of treatment on this protocol to time of the next anti-neoplastic therapy, assessed up to 2 years
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