NCT04848064

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 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

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Sponsor: John Reneau · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

PRIMARY OBJECTIVE: 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). SECONDARY OBJECTIVES: 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. CORRELATIVE OBJECTIVES: 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.

Conditions

• 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

Interventions

Type	Name	Description
DRUG	Cyclophosphamide	Given IV
DRUG	Fludarabine	Given IV
BIOLOGICAL	Mogamulizumab	Given IV
BIOLOGICAL	Natural Killer Cell Therapy	Given via infusion
OTHER	Quality-of-Life Assessment	Ancillary studies
OTHER	Questionnaire Administration	Ancillary studies

Timeline

• Start date: 2022-05-06
• Primary completion: 2026-10-30
• Completion: 2027-01-30
• First posted: 2021-04-19
• Last updated: 2026-02-10

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study