AzTrials
AzTrials

Recurrent Adult T-Cell Leukemia/LymphomaPhase 1NCT04848064

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

A Phase 1 study testing Cyclophosphamide, Fludarabine and Mogamulizumab in people with Recurrent Adult T-Cell Leukemia/Lymphoma and Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma, run by John Reneau at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cyclophosphamide, Fludarabine and Mogamulizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteUnited States
Study dates
6 May 2022to 30 Jan 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 19Show fewer
  • 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
  • Calculated creatinine clearance >= 50 ml/min (by the Crockroft-Gault equation)
  • Disease free of prior malignancies for >= 2 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast. Patients with early stage of prostate cancer under clinical surveillance without therapy are eligible. Patients with B-cell lymphomas treated with curative intent, and in remission for at least 2 years, may be in included (after discussion with principal investigator [PI])
  • Negative serum pregnancy test at the time of enrollment for females of childbearing potential. Women who can get pregnant and men with partners who can become pregnant will be asked to practice a highly effective method of birth control while participating in the study that is considered medically acceptable by the study doctor.
  • Life expectancy >= 90 days

Who cannot join

  • 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)
Show all 20Show fewer
  • Active grade II-IV acute or extensive chronic graft versus (vs.) host disease (GVHD)
  • Patients may take steroids at any dose for disease control up to 24 hours prior to study enrollment. Steroids must have been discontinued at least 1 week or 3 half-lives whichever is the longest prior to treatment in this study, per inclusion criteria above. Topical steroids are allowed for CTCL patients
  • 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
  • Recent major surgery (within 6 weeks prior to the start of study treatment) other than for diagnosis
  • Receiving immunosuppressive therapy
  • Prior therapy with mogamulizumab unless stopped previously for reasons other than progression or toxicity.
  • Pregnant or lactating, or intending to become pregnant during the study

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

The Ohio State University Comprehensive Cancer Center contact

800-293-5066

OSUCCCClinicaltrials@osumc.edu

Thomas Needham contact

thomas.needham@osumc.edu

United States1 site, 1 recruiting

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

    John C. Reneau, MD, PhD, 614-685-2239, john.reneau@osumc.edu

    John C. Reneau, MD, PhD

    Recruiting

Other trials in United States

About this study

Official title: A Pilot Phase I Trial of IL-21 Expanded, Off the Shelf, Third-Party Natural Killer (NK) Cells in Combination With Mogamulizumab in Patients With Cutaneous T-Cell Lymphomas or Adult T-Cell Leukemia/Lymphomas

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine safety, tolerability, and determine the maximum tolerated dose (MTD) of IL-21 expanded, off the shelf, third-party natural killer (NK) cells and mogamulizumab in patients with relapsed/refractory cutaneous T-cell lymphoma (CTCL) and adult T-cell leukemia/lymphoma (ATLL).

SECONDARY OBJECTIVES:

  1. To determine the overall response rate (ORR), progression free survival (PFS) and overall survival (OS) in same patient population treated with IL-21 expanded, off the shelf, third-party NK cells and mogamulizumab.

II. To determine impact of treatment on quality of life (QOL) by skindex-16 score.

CORRELATIVE OBJECTIVES:

  1. To study CCR4 expression in lymphoma cells. II. To study serum cytokine levels. III. To study trafficking of third-party NK cells to skin and tissues. IV. To study the persistence of IL-21 expanded, off the shelf, third-party NK cells by chimerism studies.

OUTLINE: This is a dose-escalation study of natural killer cells.

Patients receive mogamulizumab intravenously (IV) over 60 minutes on day -7 and fludarabine IV and cyclophosphamide IV on days -5 to -3. Patients receive NK cell infusion every 2 weeks for six infusions total starting 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.

After completion of study treatment, patients are followed up for 28-35 days and then every 3 months for 2 years.

Being tested
Cyclophosphamide, Fludarabine, Mogamulizumab, Natural Killer Cell Therapy, Quality-of-Life Assessment
Medical subject headings
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, T-Cell, Cutaneous

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • FludarabineDrug

    Also called Fluradosa

    Given IV

  • MogamulizumabBiological

    Also called 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

    Given IV

  • Natural Killer Cell TherapyBiological

    Given via infusion

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

Study groups in NCT04848064
Study groupRoleWhat they receive
Treatment (mogamulizumab, chemotherapy, NK cells)ExperimentalPatients 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.
Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Mogamulizumab; Biological: Natural Killer Cell Therapy; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to day 84

Secondary outcomes (6)

  1. Overall response rate (ORR)

    Will be summarized in a descriptive manner. The ORR will be calculated as the proportion of patients who achieve complete response /partial response, and provided with 95% confidence interval.

    Measured: Up to 4 months

  2. Progression free survival

    Will be estimated using the method of Kaplan-Meier.

    Measured: 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

  3. Overall survival

    Will be estimated using the method of Kaplan-Meier.

    Measured: 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

  4. Natural Killer (NK)-cell numerical expansion in vivo

    Peripheral blood will be obtained before therapy, during the NK cell treatment period (day +42), after NK cell treatment (day +84), and at the time of progression. Donor NK-cell expansion will be defined as an absolute circulating donor-derived NK cell count that increases above the post-infusion level. Standard chimerism methods will be employed to determine origin and number of circulating NK cells.

    Measured: Baseline to day 84

  5. Analysis of cytokine levels

    Peripheral blood will be obtained before therapy, during the NK cell treatment period (day +42), after NK cell treatment (day +84), and at the time of relapse. Cytokine levels will be reported as absolute values and will be correlated with response to treatment and skindex-16 scores.

    Measured: Baseline to day 84

  6. Quality of life analysis

    Skindex-16 questionnaires will be obtained before therapy, during the NK cell treatment period (day +42), and after NK cell treatment (day +84, and every 2 months while on moga treatment). Skindex will be reported as total and specific domain scores, and described using graphical manners to show the pattern of change over treatment course.

    Measured: Baseline to day 84

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Apr 2021
  2. Study start6 May 2022
  3. Primary completion30 Oct 2026 (estimated)
  4. Study completion30 Jan 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04848064
Sponsor's protocol ID
OSU-20103
Other IDs
NCI-2021-01375
Status last verified
Feb 2026
First submitted
13 Apr 2021
Last updated
10 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cyclophosphamide, Fludarabine and Mogamulizumab in people with Recurrent Adult T-Cell Leukemia/Lymphoma and Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma, run by John Reneau at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 10 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact The Ohio State University Comprehensive Cancer Center (800-293-5066, OSUCCCClinicaltrials@osumc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (time frame: Up to day 84). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04848064.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in