Third-Party Natural Killer Cells and Mogamulizumab for the Treatment of Relapsed or Refractory Cutaneous T-cell Lymphomas or Adult T-Cell Leukemia/Lymphoma
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|ClinicalTrials.gov Identifier: NCT04848064|
Recruitment Status : Not yet recruiting
First Posted : April 19, 2021
Last Update Posted : April 19, 2021
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Adult T-Cell Leukemia/Lymphoma Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma Refractory Adult T-Cell Leukemia/Lymphoma Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma||Drug: Cyclophosphamide Drug: Fludarabine Biological: Mogamulizumab Biological: Natural Killer Cell Therapy Other: Quality-of-Life Assessment Other: Questionnaire Administration||Phase 1|
I. 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).
I. 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.
I. 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Estimated Study Start Date :||June 1, 2021|
|Estimated Primary Completion Date :||December 31, 2023|
|Estimated Study Completion Date :||December 31, 2024|
Experimental: Treatment (mogamulizumab, chemotherapy, NK cells)
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.
Other Name: Fluradosa
Biological: Natural Killer Cell Therapy
Given via infusion
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
Other: Questionnaire Administration
- Incidence of adverse events [ Time Frame: Up to day 84 ]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.
- Overall response rate (ORR) [ Time Frame: Up to 4 months ]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.
- Progression free survival [ Time Frame: 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 ]Will be estimated using the method of Kaplan-Meier.
- Overall survival [ Time Frame: 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 ]Will be estimated using the method of Kaplan-Meier.
- Natural Killer (NK)-cell numerical expansion in vivo [ Time Frame: Baseline to day 84 ]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.
- Analysis of cytokine levels [ Time Frame: Baseline to day 84 ]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.
- Quality of life analysis [ Time Frame: Baseline to day 84 ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04848064
|Contact: The Ohio State University Comprehensive Cancer Center||800-293-5066||OSUCCCClinicaltrials@osumc.edu|
|Contact: Wesley Fergusonemail@example.com|
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center|
|Columbus, Ohio, United States, 43210|
|Contact: John C. Reneau 614-685-2239 firstname.lastname@example.org|
|Principal Investigator: John C. Reneau|
|Principal Investigator:||John C Reneau, MD||Ohio State University Comprehensive Cancer Center|