NCT02950220

Pembrolizumab and Ibrutinib in Treating Patients With Relapsed or Refractory Non-Hodgkin Lymphoma

A Phase I/Ib Study of the PD-1 Antibody Pembrolizumab in Combination With Ibrutinib in Relapsed/Refractory Non-Hodgkin's Lymphoma (NHL)

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 2 (actual)
• Sponsor: Kami Maddocks · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I/Ib trial studies the side effects and best dose of ibrutinib when given together with pembrolizumab and to see how well they work in treating patients with non-Hodgkin lymphoma that has come back or does not respond to treatment. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Given pembrolizumab and ibrutinib may work better in treating patients with non-Hodgkin lymphoma.

Detailed description

PRIMARY OBJECTIVES: I. To determine the safety and tolerability of the combination of ibrutinib and pembrolizumab in patients with relapsed/refractory non-Hodgkin lymphoma (NHL). II. To determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of the combination of ibrutinib and pembrolizumab in patients with relapsed/refractory NHL. III. To evaluate the efficacy of the combination of ibrutinib and pembrolizumab in patients with relapsed/refractory NHL. SECONDARY OBJECTIVES: I. To determine the overall response rate (ORR), duration of response, progression-free survival and overall survival of the combination of ibrutinib and pembrolizumab in patients with relapsed/refractory NHL. TERTIARY OBJECTIVES: I. To explore the relationship between prognostic parameters including ki-67 staining, PD-1 staining and cell of origin (activated B-cell or ABC versus germinal center B-cell or GCB) with ORR to the combination of ibrutinib and pembrolizumab in patients with relapsed/refractory NHL. II. To determine relationship between gene mutations and resistance to therapy with the combination of ibrutinib and pembrolizumab in patients with relapsed/refractory NHL (BTK, PLC gamma 2, PD-1). III. To evaluate and monitor effects on B-, T-, and natural killer (NK)-cell function with the combination of ibrutinib and pembrolizumab in patients with relapsed/refractory NHL. OUTLINE: This is a phase I, dose-escalation study of ibrutinib followed by a phase Ib study. Patients receive ibrutinib orally (PO) daily on days 1-21 and pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days, and then every 3 months for 2 years and every 6 months for 3 years.

Conditions

• B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma
• Grade 1 Follicular Lymphoma
• Grade 2 Follicular Lymphoma
• Grade 3a Follicular Lymphoma
• Mediastinal Lymphoma
• Recurrent B-Cell Non-Hodgkin Lymphoma
• Recurrent Burkitt Lymphoma
• Recurrent Diffuse Large B-Cell Lymphoma
• Recurrent Follicular Lymphoma
• Recurrent Lymphoplasmacytic Lymphoma
• Recurrent Mantle Cell Lymphoma
• Recurrent Marginal Zone Lymphoma
• Recurrent Waldenstrom Macroglobulinemia
• Refractory B-Cell Non-Hodgkin Lymphoma
• Refractory Burkitt Lymphoma
• Refractory Diffuse Large B-Cell Lymphoma
• Refractory Follicular Lymphoma
• Refractory Lymphoplasmacytic Lymphoma
• Refractory Mantle Cell Lymphoma

Interventions

Type	Name	Description
DRUG	Ibrutinib	Given PO
OTHER	Laboratory Biomarker Analysis	Correlative studies
BIOLOGICAL	Pembrolizumab	Given IV

Timeline

• Start date: 2017-01-12
• Primary completion: 2018-11-19
• Completion: 2019-01-03
• First posted: 2016-11-01
• Last updated: 2019-07-30

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study