NCT04541017

Brief 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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
8

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Apr 2021

Typical duration for phase_1

Geographic Reach
1 country

18 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 5, 2020

Completed
4 days until next milestone

First Posted

Study publicly available on registry

September 9, 2020

Completed
7 months until next milestone

Study Start

First participant enrolled

April 6, 2021

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 24, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 24, 2024

Completed
12 months until next milestone

Results Posted

Study results publicly available

October 16, 2025

Completed
Last Updated

October 16, 2025

Status Verified

September 1, 2025

Enrollment Period

3.6 years

First QC Date

September 5, 2020

Results QC Date

September 30, 2025

Last Update Submit

September 30, 2025

Conditions

Outcome Measures

Primary Outcomes (2)

  • 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.

    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).

    At 6 months

Secondary Outcomes (6)

  • Overall Response Rate (ORR) (Phase Ib)

    Up to 2 years

  • Overall Response Rate at 4 Months (ORR4) (Phase II)

    At 4 months

  • Overall Response Rate at 12 Months (ORR12) (Phase II)

    At 12 months

  • Progression-free Survival (PFS) (Phase II)

    From start of treatment to time of progression or death, whichever occurs first, assessed up to 2 years

  • Duration of Response (DOR) (Phase II)

    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

  • +1 more secondary outcomes

Study Arms (2)

Arm I (magrolimab, mogamulizumab), Phase Ib and Phase II

EXPERIMENTAL

Patients receive magrolimab IV over 2-3 hours weekly during cycles 1-2, then 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 PET/CT or diagnostic CT, blood sample collection, and may undergo a skin punch biopsy during screening and on study.

Procedure: Biospecimen CollectionProcedure: Computed TomographyBiological: MagrolimabBiological: MogamulizumabProcedure: Positron Emission TomographyProcedure: Punch Biopsy

Arm II (mogamulizumab), Phase II

ACTIVE COMPARATOR

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 PD or have received at least 6 full treatment cycles and have 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.

Procedure: Biospecimen CollectionProcedure: Computed TomographyBiological: MogamulizumabProcedure: Positron Emission TomographyProcedure: Punch Biopsy

Interventions

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection
Arm I (magrolimab, mogamulizumab), Phase Ib and Phase IIArm II (mogamulizumab), Phase II

Undergo PET/CT or diagnostic CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography
Arm I (magrolimab, mogamulizumab), Phase Ib and Phase IIArm II (mogamulizumab), Phase II
MagrolimabBIOLOGICAL

Given IV

Also known as: Hu5F9-G4, ONO 7913, ONO-7913, ONO7913
Arm I (magrolimab, mogamulizumab), Phase Ib and Phase II
MogamulizumabBIOLOGICAL

Given IV

Also known as: Immunoglobulin G1, Anti-(CC Chemokine Receptor CCR4) (Human-Mouse Monoclonal KW-0761 Heavy Chain), Disulfide With Human-Mouse Monoclonal KW-0761 Kappa-Chain, Dimer, KM8761, KW 0761, KW-0761, KW0761, Mogamulizumab-kpkc, Poteligeo
Arm I (magrolimab, mogamulizumab), Phase Ib and Phase IIArm II (mogamulizumab), Phase II

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT
Arm I (magrolimab, mogamulizumab), Phase Ib and Phase IIArm II (mogamulizumab), Phase II
Punch BiopsyPROCEDURE

Undergo skin punch biopsy

Also known as: BIOPSY, PUNCH, Punch Biopsy of Skin
Arm I (magrolimab, mogamulizumab), Phase Ib and Phase IIArm II (mogamulizumab), Phase II

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Diagnosis of either mycosis fungoides (MF) or Sezary syndrome (SS) by the World Health Organization (WHO) 2016 classification (Swerdlow et al., 2017), stage IB-IV by modified International Society for Cutaneous Lymphomas (ISCL)/ European Organization of Research and Treatment of Cancer (EORTC) classification (Olsen et al., 2011), without large cell transformation (LCT) at the time of screening. Patients with a history of prior LCT are permitted
  • Patients must have had at least one prior course of systemic therapy
  • Age \>= 18 years
  • Because no dosing or adverse event data are currently available on the use of Hu5F9-G4 (magrolimab) in combination with mogamulizumab in patients \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
  • Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
  • Hemoglobin \>= 9.5 g/dL and transfusion independence (defined as not requiring more than 2 units of red blood cell \[RBC\] transfusions during the 4-week period prior to screening)
  • Absolute neutrophil count \>= 1,000/mcL
  • Platelets \>= 75,000/mcL
  • Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) except for subjects with Gilbert's syndrome or genetic equivalent
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional ULN
  • Glomerular filtration rate (GFR) \>= 40 mL/min/1.73 m\^2 by the Cockcroft-Gault formula
  • Patients must meet the following minimum wash-out window from previous treatments to the first treatment
  • \>= 3 weeks for systemic anti-cancer therapies
  • \>= 2 weeks for phototherapy, local radiation therapy, topical high potency corticosteroid, topical retinoid, topical nitrogen mustard, or topical toll-like receptor (TLR)-agonist
  • \>= 12 weeks for total skin electron beam therapy Participants with rapidly progressive malignant disease may be enrolled prior to completion of the above periods with approval of the protocol director
  • +11 more criteria

You may not qualify if:

  • Prior treatment with Hu5F9-G4 (magrolimab) or any agent targeting CD47-SIRPalpha
  • Prior progression of disease with mogamulizumab
  • Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia and lymphopenia (any grade permitted). Residual peripheral neuropathy must have improved to grade 2 or better
  • Patients who are receiving any other investigational agents
  • Allogeneic hematopoietic stem cell transplant recipients with any graft-versus-host disease within the previous 3 months or requiring immunosuppression
  • Active autoimmune disease that has required systemic immunosuppressive medication within the previous 3 months
  • Active herpes simplex or herpes zoster. Subjects on prophylaxis for herpes who have no active signs of active infection, and whose last active infection was more than 6 months ago, may enter the study, and should continue to take the prescribed medication for the duration of the study
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to Hu5F9-G4 (magrolimab), other monoclonal antibodies, or other agents (mogamulizumab) used in study
  • Significant cardiopulmonary disease defined as
  • Acute myocardial infarction within the last 6 months
  • Unstable angina
  • Congestive heart failure New York Heart Association (NYHA) class III-IV
  • Patients with uncontrolled intercurrent illness requiring antibiotics. Patients on prophylactic antibiotics for non-complicated staphylococcus colonization/infection are eligible
  • Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are excluded
  • Patients with psychiatric illness/social situations or substance abuse that would limit compliance with study requirements
  • +12 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (18)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Los Angeles General Medical Center

Los Angeles, California, 90033, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Stanford Cancer Institute Palo Alto

Palo Alto, California, 94304, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

NYP/Weill Cornell Medical Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Mycosis FungoidesSezary Syndrome

Interventions

Specimen HandlingmagrolimabmogamulizumabImmunoglobulin GDisulfidesMagnetic Resonance SpectroscopyBiopsy

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell, CutaneousLymphoma, T-CellLymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisInvestigative TechniquesImmunoglobulin IsotypesAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsSulfidesAnionsIonsElectrolytesInorganic ChemicalsHydrogen SulfideSulfur CompoundsOrganic ChemicalsSpectrum AnalysisChemistry Techniques, AnalyticalCytodiagnosisCytological TechniquesDiagnostic Techniques, SurgicalSurgical Procedures, Operative

Results Point of Contact

Title
Paul Frankel, Ph.D.
Organization
City of Hope

Study Officials

  • Michael S Khodadoust

    City of Hope Comprehensive Cancer Center LAO

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 5, 2020

First Posted

September 9, 2020

Study Start

April 6, 2021

Primary Completion

October 24, 2024

Study Completion

October 24, 2024

Last Updated

October 16, 2025

Results First Posted

October 16, 2025

Record last verified: 2025-09

Data Sharing

IPD Sharing
Will share

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

More information

Locations