Third-Party Natural Killer Cells and Mogamulizumab for the Treatment of Relapsed or Refractory Cutaneous T-cell Lymphomas or Adult T-Cell Leukemia/Lymphoma

NCT04848064 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-20103NCI-2021-01375
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial is to find out the best dose, possible benefits and/or side effects of third-party natural killer cells in combination with mogamulizumab in treating patients with cutaneous T-cell lymphoma or adult T-cell leukemia/lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Immunotherapy with third-party natural killer cells, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Mogamulizumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving third-party natural killer cells in combination with mogamulizumab may kill more cancer cells.

Conditions

Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Adult T-Cell Leukemia/Lymphoma; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events

  Toxicities will be captured by Common Terminology Criteria for Adverse Events version 5. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. The incidence of severe adverse events or toxicities will be described. Will assess the proportion of patients who experience grade 3 or higher non-hematologic toxicity.

  Up to day 84

Secondary Outcomes (6)

• Overall response rate (ORR)

  Up to 4 months

• Progression free survival

  From start of study treatment (from the first dose mogamulizumab [moga]) to first documentation of tumor progression (including radiographic and clinical progression) or to death due to any cause, whichever comes first, assessed up to 2 years

• Overall survival

  From start of study treatment to date of death due to any cause. In the absence of confirmation of death, survival time will be censored at the last date the patient is known to be alive, whichever comes first, assessed up to 2 years

• Natural Killer (NK)-cell numerical expansion in vivo

  Baseline to day 84

• Analysis of cytokine levels

  Baseline to day 84

Study Arms (1)

Treatment (mogamulizumab, chemotherapy, NK cells)

EXPERIMENTAL

Patients receive mogamulizumab IV over 60 minutes on day -7 and fludarabine IV and cyclophosphamide IV on days -5 to -3. Patients receive NK cell infusion on day 0. Patients then receive mogamulizumab IV over 60 minutes on days 0, 7, 14, and 28, then every 2 weeks thereafter in the absence of disease progression or unacceptable toxicity.

Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Mogamulizumab; Biological: Natural Killer Cell Therapy; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

Natural Killer Cell Therapy BIOLOGICAL

Given via infusion

Treatment (mogamulizumab, chemotherapy, NK cells)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (mogamulizumab, chemotherapy, NK cells)

Questionnaire Administration OTHER

Ancillary studies

Treatment (mogamulizumab, chemotherapy, NK cells)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (mogamulizumab, chemotherapy, NK cells)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (mogamulizumab, chemotherapy, NK cells)

Mogamulizumab BIOLOGICAL

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, Mogamulizumab-kpkc, Poteligeo

Treatment (mogamulizumab, chemotherapy, NK cells)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand and voluntarily sign an informed consent form
• Age \>= 18 years at the time of signing the informed consent form
• Able to adhere to the study visit schedule and other protocol requirements
• Biopsy-proven, measurable, stage IB-IVB relapsed or refractory cutaneous T-cell lymphoma after 1 prior line of systemic therapy
• Note: extracorporeal photopheresis will be considered a systemic therapy for this study
• Patients with large cell transformation of cutaneous T cell lymphoma are eligible
• Patients with adult T-cell leukemia/lymphoma (ATLL) of any stage and any subtypes. Patient must have had at least one standard chemotherapy and measurable disease at the time of enrollment
• Patients who relapsed after autologous or allogeneic stem cell transplant are eligible
• All cancer therapy, including radiation, topical steroid, and chemotherapy must have been discontinued at least 1 week or 3 half-lives whichever is the longest prior to treatment in this study. The only exceptions are participants who are symptomatic from their skin lesions and have been on corticosteroids for prolonged periods of time (\> 60 days) without change. These patients may continue use of either systemic steroids (equivalent to \< 10 mg per day of prednisone) or topical steroids if the frequency and dosage steroids has not changed for 21 days prior to the study. These participants should continue on the same dose of systemic/topical steroid throughout the study period unless they achieve a complete response at which time steroids can be tapered or discontinued. Patients are allowed to continue any medications with known activity in T cell lymphomas at the pre-enrollment doses for conditions other than T cell lymphomas (ie, steroids for sarcoidosis), as long as there is evidence of T cell lymphoma progression while patients were on these agents
• Eastern Cooperative Oncology Group (ECOG) performance status of =\< 1 at study entry
• Absolute neutrophil count \>= 1000/mm\^3
• Platelet count \>= 50,000/mm\^3
• Total bilirubin =\< 2 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and Alanine Aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 3 x ULN
• AST (SGOT) and ALT (SGPT) =\< 5 x ULN in patients with documented hepatic involvement by lymphoma

You may not qualify if:

• Investigational therapies in the 2 weeks prior to beginning treatment on trial
• Patients with active central nervous system (CNS) involvement with lymphoma
• Patients with known human immunodeficiency virus (HIV) infection with CD4 \< 350
• Patients who had solid organ transplants
• Evidence of active hepatitis B infection, based on positive surface antigen or hepatitis B deoxyribonucleic acid (DNA) polymerase chain reaction (PCR), or active hepatitis C infection based on positive PCR. Patients who are hepatitis B core antibody positive must take prophylaxis with lamivudine or equivalent and be willing to undergo monthly hepatitis B DNA PCR testing
• Present or history of progressive multifocal leukoencephalopathy (PML)
• Active grade II-IV acute or extensive chronic graft versus (vs.) host disease (GVHD)
• Any illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety
• A cardiovascular disability status of New York Heart Association class \>= 2
• History of severe allergic reactions to humanized monoclonal antibodies
• History of other malignancy that could affect compliance with the protocol or interpretation of results. Patients with a history of curatively treated basal or squamous cell carcinoma or Stage 1 melanoma of the skin or in situ carcinoma of the cervix are eligible. Patients with early stage of prostate cancer under clinical surveillance without therapy are eligible
• Known hypersensitivity to any of the study drugs or analogs
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks prior study therapy
• Clinically significant history of liver disease, including viral or other hepatitis, or cirrhosis
• Receipt of live-virus vaccines within 28 days prior to the initiation of study treatment or need for live-virus vaccines at any time during study treatment

Sponsors & Collaborators

• John Reneau: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Related Links

• The Jamesline

MeSH Terms

Conditions

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, T-Cell, Cutaneous

Interventions

Cyclophosphamide; fludarabine; mogamulizumab; Immunoglobulin G; Disulfides

Condition Hierarchy (Ancestors)

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds

Study Officials

• John C Reneau, MD, PhD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

The Ohio State University Comprehensive Cancer Center

CONTACT

800-293-5066; OSUCCCClinicaltrials@osumc.edu

Thomas Needham

CONTACT

thomas.needham@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 13, 2021
• First Posted: April 19, 2021
• Study Start: May 6, 2022
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): January 30, 2027
• Last Updated: February 10, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)