Mogamulizumab and Pembrolizumab in Treating Patients With Relapsed or Refractory Diffuse Large B Cell Lymphoma

Refractory Diffuse Large B-Cell Lymphoma Clinical Trial

Official title: A Phase I and Randomized Phase II Study of KW-0761 (Mogamulizumab) and MK-3475 (Pembrolizumab) in Relapsed, Refractory Diffuse Large-B Cell Lymphoma

Status Completed

Clinical Trial Summary

This phase I/II trial studies the best dose and side effects of mogamulizumab in combination with pembrolizumab and to see how well they work in treating patients with diffuse large B cell lymphoma that have come back after a period of improvement (relapsed) or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as mogamulizumab and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of KW-0761 (mogamulizumab) when administered in combination with MK-3475 (pembrolizumab) in patients with relapsed, refractory diffuse large B-cell lymphoma. (Phase I) II. To assess the safety and tolerability of KW-0761 (mogamulizumab) when administered in combination with MK-3475 (pembrolizumab) in patients with relapsed, refractory diffuse large B-cell lymphoma. (Phase I) III. To assess the progression-free survival of KW-0761 (mogamulizumab) when administered in combination with MK-3475 (pembrolizumab) compared to MK-3475 (pembrolizumab) alone in patients with relapsed and refractory diffuse large B-cell lymphomas. (Phase II)

SECONDARY OBJECTIVES:

I. To observe and record anti-tumor activity. (Phase I) II. To assess the overall response rate, complete response rate, partial response rate, duration of response of KW-0761 (mogamulizumab) and MK-3475 (pembrolizumab) compared to MK-3475 (pembrolizumab) alone in patients with relapsed and refractory diffuse large B-cell lymphomas. (Phase II)

EXPLORATORY OBJECTIVES:

I. To determine whether the progression-free survival of KW-0761 (mogamulizumab) and MK-3475 (pembrolizumab) when administered to patients with relapsed and refractory diffuse large B-cell lymphomas differs based on the presence or absence of mutations in B2M or CD58 or amplifications in PD-L1.

II. To determine whether the progression-free survival of KW-0761 (mogamulizumab) and MK-3475 (pembrolizumab) when administered to patients with relapsed and refractory diffuse large B-cell lymphomas differs based on changes in CD8 T-cell, natural killer (NK) cell, and FoxP3+ regulatory T cell (Treg) prevalence in response to therapy as measured by immunohistochemistry.

III. To determine whether KW-0761 (mogamulizumab) and MK-3475 (pembrolizumab) alters the prevalence of peripheral blood CCR4+/FoxP3+ regulatory T-cells as well as effector CD4 and CD8 T-cells by multi-parametric flow cytometry.

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

ARM I: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and mogamulizumab IV over 60 minutes on days 1, 8, and 15 of cycle 1, then day 1 of subsequent courses. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks. ;

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Non-Hodgkin
• Recurrence
• Recurrent Diffuse Large B-Cell Lymphoma
• Recurrent High Grade B-Cell Lymphoma
• Recurrent Transformed B-Cell Non-Hodgkin Lymphoma
• Refractory Diffuse Large B-Cell Lymphoma
• Refractory High Grade B-Cell Lymphoma
• Refractory Transformed B-Cell Non-Hodgkin Lymphoma

• NCT number: NCT03309878
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: October 24, 2018
• Completion date: April 11, 2023