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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

2019-12-10 01:21:18 | BioPortfolio

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 IL-15 and mogamulizumab are safe and effective to treat people with 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 HIV, hepatitis B and C), urine, lung, and heart tests

Bone marrow tests (if needed): A needle inserted in the participant s hip will take a small amount of marrow.

CT, PET and/or MRI scans

Tumor biopsy (if needed): A needle will take out a small piece of the participant s 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.

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 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 NK cells, monocytes and long- term CD8+ 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

- 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 MTD of dose-escalated 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.

Study Design

Conditions

Adult T-Cell Lymphoma/Leukemia

Intervention

rhIL-15, Mogamulizumab

Location

National Institutes of Health Clinical Center
Bethesda
Maryland
United States
20892

Status

Not yet recruiting

Source

National Institutes of Health Clinical Center (CC)

Results (where available)

View Results

Links

Published on BioPortfolio: 2019-12-10T01:21:18-0500

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Medical and Biotech [MESH] Definitions

A genus in the family RETROVIRIDAE consisting of exogenous horizontally-transmitted viruses found in a few groups of mammals. Infections caused by these viruses include human B- or adult T-cell leukemia/lymphoma (LEUKEMIA-LYMPHOMA, T-CELL, ACUTE, HTLV-I-ASSOCIATED), and bovine leukemia (ENZOOTIC BOVINE LEUKOSIS). The type species is LEUKEMIA VIRUS, BOVINE.

A strain of PRIMATE T-LYMPHOTROPIC VIRUS 1 isolated from mature T4 cells in patients with T-lymphoproliferation malignancies. It causes adult T-cell leukemia (LEUKEMIA-LYMPHOMA, T-CELL, ACUTE, HTLV-I-ASSOCIATED), T-cell lymphoma (LYMPHOMA, T-CELL), and is involved in mycosis fungoides, SEZARY SYNDROME and tropical spastic paraparesis (PARAPARESIS, TROPICAL SPASTIC).

Aggressive T-Cell malignancy with adult onset, caused by HUMAN T-LYMPHOTROPIC VIRUS 1. It is endemic in Japan, the Caribbean basin, Southeastern United States, Hawaii, and parts of Central and South America and sub-Saharan Africa.

A leukemia/lymphoma found predominately in children and young adults and characterized LYMPHADENOPATHY and THYMUS GLAND involvement. It most frequently presents as a lymphoma, but a leukemic progression in the bone marrow is common.

A leukemia/lymphoma found predominately in children and adolescents and characterized by a high number of lymphoblasts and solid tumor lesions. Frequent sites involve LYMPH NODES, skin, and bones. It most commonly presents as leukemia.

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