Durvalumab With or Without Lenalidomide in Treating Patients With Relapsed or Refractory Cutaneous or Peripheral T Cell Lymphoma

Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma Clinical Trial

Official title: A Phase 1/2 Trial of Durvalumab (MEDI4736) When Given as a Single Agent or in Combination With Lenalidomide in Patients With Relapsed/ Refractory Peripheral T-cell Lymphoma, Including Cutaneous T-cell Lymphoma

Status Recruiting

Clinical Trial Summary

This randomized phase I/II trial studies the best dose and side effects of durvalumab and to see how well it works with or without lenalidomide in treating patients with cutaneous or peripheral T cell lymphoma that has come back and does not respond to treatment. Monoclonal antibodies, such as durvalumab, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving durvalumab and lenalidomide may work better in treating patients with cutaneous or peripheral T cell lymphoma.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (recommended phase 2 dose, RP2D) of lenalidomide, when given in combination with fixed-dose durvalumab. (Phase 1) II. To assess the safety and tolerability of the lenalidomide/durvalumab regimen, and accompanying dose modification plan, by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration. (Phase 1) III. To evaluate the anti-tumor activity durvalumab (MEDI4736) as single agent therapy and as part of combination therapy (+lenalidomide); activity assessed by overall response rate (ORR). (Phase 2)

SECONDARY OBJECTIVES:

I. To estimate and assess response duration and survival probabilities (overall and event-free). (Phase 2) II. To summarize and assess toxicities by type, frequency, severity, attribution, time course and duration. (Phase 2) III. To assess clinically meaningful reduction in pruritus (CMRP) in patients with CTCL (critical quality of life measure). (Phase 2)

TERTIARY OBJECTIVES:

I. To identify the malignant CD4+ T cells within the skin microenvironment. II. To characterize the spatial and functional relationship of malignant T cells with other immune cells, their expression of key immune checkpoints and correlate with response.

III. To identify aberrantly expressed micro(mi) ribonucleic acid (RNA)s involved in cutaneous T-cell lymphoma (CTCL) and messenger (m)RNAs that may predict response and/or treatment-related toxicity.

IV. To evaluate whether or not the identified miRNAs are involved in regulating key immune checkpoints.

OUTLINE: This is a phase I, dose-escalation study of lenalidomide followed by a phase II study. Patients are randomized to 1 of 2 arms,

ARM I: Patients receive durvalumab intravenously (IV) over 1 hour on day 1. Treatment repeats every 28 days (+/- 3) for up to 13 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive durvalumab IV over 1 hour on day 1 and lenalidomide orally (PO) once daily (QD) on days 1-21. Treatment repeats every 28 (+/- 3) days for up to 13 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for up to 12 months. ;

Related Conditions & MeSH terms

• Folliculotropic Mycosis Fungoides
• Lymphoma
• Lymphoma, Non-Hodgkin
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Cutaneous
• Lymphoma, T-Cell, Peripheral
• Mycoses
• Mycosis Fungoides
• Recurrence
• Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma
• Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma
• Recurrent Mycosis Fungoides
• Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma
• Refractory Mycosis Fungoides
• Refractory Peripheral T-Cell Lymphoma, Not Otherwise Specified
• Sezary Syndrome

• NCT number: NCT03011814
• Study type: Interventional
• Source: City of Hope Medical Center
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 8, 2017
• Completion date: June 1, 2026