Phase I Study of Recombinant Human IL-15 (rhIL-15) and Mogamulizumab for People With Refractory or Relapsed Adult T-Cell Leukemia and Mycosis Fungoides/Sezary Syndrome

Mycosis Fungoides Clinical Trial

Official title: Phase 1 Study of Recombinant Human IL-15 (rhIL-15) and Mogamulizumab for Patients With Refractory or Relapsed Adult T-Cell Leukemia and Mycosis Fungoides/Sezary Syndrome

Status Completed

Clinical Trial Summary

Background: Adult T-cell leukemia/lymphoma (ATLL) and mycosis fungoides/Sezary syndrome (MF/SS) are cancers that form in the T cells, a type of white blood cell that helps with the body's immune response. A combination of drugs might be able to better treat these cancers than existing therapies. Objective: To test if the drugs interleukin-15 (IL-15) and mogamulizumab are safe and effective to treat people with Adult T-Cell Leukemia and Mycosis Fungoides/Sezary Syndrome (ATLL or MF/SS). Eligibility: People ages 18 and older with relapsed ATLL or MF/SS that has not responded to at least one standard treatment Design: Participants will be screened with: Medical history Physical exam Blood (including human immunodeficiency virus (HIV), hepatitis B and C), urine, lung, and heart tests Bone marrow tests (if needed): A needle inserted in the participants hip will take a small amount of marrow. Computed tomography (CT), positron emission tomography (PET) and/or magnetic resonance imaging (MRI) scans Tumor biopsy (if needed): A needle will take out a small piece of the participants tumor. Participants will get the study drugs by vein for up to six 28-day cycles. They will get IL-15 the first 5 days of each cycle. They will get mogamulizumab on days 1, 8, 15, and 22 of cycle 1 and days 1 and 15 of the other cycles. They will be hospitalized for 1 week in cycle 1. They may need to get a midline catheter. This is a soft tube put into a vein leading to the heart. Participants will have repeats of the screening tests throughout the study. After treatment, participants will have visits every 60 days for 6 months, every 90 days for 2 years, and then every 6 months for 2 years.

Clinical Trial Description

Background: - Advanced mycosis fungoides, its leukemic form Sezary syndrome (MF/SS), and adult T- cell leukemia/lymphoma (ATLL) are all aggressive mature T-cell malignancies which are considered incurable without an allogeneic stem cell transplant. - Mogamulizumab is a defucosylated monoclonal antibody directed towards C-C Motif Chemokine Receptor 4 (CCR4), a chemokine receptor expressed by the majority of MS/SS and ATLL cells. It is approved by the United States Food and Drug Administration for treatment of relapsed MF/SS and is recommended by the National Comprehensive Cancer Network for treatment of ATLL. - Defucosylation of mogamulizumab is thought to enhance its capacity for antibody- dependent cell cytotoxicity (ADCC), which is mediated by natural killer (NK) cells and macrophages. - The immunologic effects of recombinant human Interleukin-15 (rhIL-15), a stimulatory cytokine that promotes the differentiation and activation of natural killer (NK) cells, monocytes and long- term cluster of differentiation 8 (CD) 8+ memory T-cells, has been assessed in several phase I trials in cancer patients. - Concomitant administration of rhIL-15 with mogamulizumab may further enhance the ADCC capacity of the antibody and result in improved efficacy for patients with CCR4- expressing cancers. Objectives: -To determine the safety and toxicity profile and the maximum tolerated dose (MTD) of continuous intravenous infusion (civ) rhIL-15 administration in combination with standard intravenous (IV) mogamulizumab treatment Eligibility: - Age greater than or equal to 18 years of age - Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 1 - Histologically or cytologically confirmed mycosis fungoides/S(SqrRoot)(Copyright)zary syndrome or adult T- cell leukemia/lymphoma relapsed after or refractory to at least one line of systemic treatment. - Adequate organ and marrow function Design: - Open-label, single-center, non-randomized phase I study - Standard "3 + 3" design will be used to determine the maximum tolerated dose (MTD) of dose-escalated recombinant human Interleukin-15 (rhIL-15) with fixed dose of mogamulizumab, with an expansion cohort at the MTD - Maximum 6 cycles (28-day cycles) of combination therapy - To explore all dose levels, including further evaluation in a dose expansion cohort, and to account for unevaluable patients the accrual ceiling will be set at 20 patients. ;

Related Conditions & MeSH terms

• Adult T-Cell Lymphoma/Leukemia
• Leukemia
• Leukemia, T-Cell
• Leukemia-Lymphoma, Adult T-Cell
• Mycoses
• Mycosis Fungoides
• Sezary Syndrome
• Syndrome

• NCT number: NCT04185220
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 1
• Start date: February 26, 2020
• Completion date: May 18, 2022