NCT04541017

Testing the Addition of an Anti-cancer Drug, Hu5F9-G4 (Magrolimab), to the Usual Chemotherapy Treatment (Mogamulizumab) in T-Cell (a Type of Immune Cell) Lymphoma That Has Returned After Treatment or Does Not Respond to Treatment

A Phase 1b/2 Study of Hu5F9-G4 (Magrolimab) in Combination With Mogamulizumab in Relapsed/Refractory Treated T-Cell Lymphoma

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Mycosis Fungoides
• Recurrent Mycosis Fungoides
• Recurrent Mycosis Fungoides and Sezary Syndrome
• Recurrent Sezary Syndrome
• Refractory Mycosis Fungoides
• Refractory Mycosis Fungoides and Sezary Syndrome
• Refractory Sezary Syndrome
• Sezary Syndrome
• Stage IB Mycosis Fungoides and Sezary Syndrome AJCC v8
• Stage II Mycosis Fungoides and Sezary Syndrome AJCC v8
• Stage III Mycosis Fungoides and Sezary Syndrome AJCC v8
• Stage IV Mycosis Fungoides and Sezary Syndrome AJCC v8

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Computed Tomography	Undergo PET/CT or diagnostic CT
BIOLOGICAL	Magrolimab	Given IV
BIOLOGICAL	Mogamulizumab	Given IV
PROCEDURE	Positron Emission Tomography	Undergo PET/CT
PROCEDURE	Punch Biopsy	Undergo skin punch biopsy

Timeline

• Start date: 2021-04-06
• Primary completion: 2024-10-24
• Completion: 2024-10-24
• First posted: 2020-09-09
• Last updated: 2025-10-16
• Results posted: 2025-10-16

Locations

18 sites across 1 country: United States

Regulatory

• FDA-regulated drug study