NCT04781855

Ipilimumab, Ibrutinib, and Nivolumab for the Treatment of Chronic Lymphocytic Leukemia and Richter Transformation

Ipilimumab Combined With Ibrutinib and Nivolumab for Patients With Chronic Lymphocytic Leukemia (CLL) and Richter Transformation (RT)

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I/Ib trial evaluates the best dose and side effects of ipilimumab in combination with either ibrutinib alone or with ibrutinib and nivolumab in treating patients with chronic lymphocytic leukemia (CLL) and Richter transformation (RT). Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and 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. Giving ipilimumab with either ibrutinib alone or with ibrutinib and nivolumab may help control CLL and RT.

Detailed description

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of ipilimumab in combination with ibrutinib in patients with CLL/small lymphocytic lymphoma (SLL)/RT. (Part A) II. To determine the MTD and DLT of ipilimumab in combination with nivolumab and ibrutinib in patients with CLL/SLL/RT. (Part B) SECONDARY OBJECTIVES: I. To determine the efficacy (response rate, defined as complete response \[CR\] + complete response with incomplete marrow recovery \[CRi\] + partial response \[PR\]) of the combination therapy. II. To determine the progression-free survival and overall survival of the combination therapy. EXPLORATORY OBJECTIVE: I. To study immunological and molecular changes in peripheral blood, lymph node, and bone marrow in response to the combination therapy. OUTLINE: This is a dose-escalation study of ipilimumab followed by a dose-expansion study. Patients are assigned to 1 of 2 parts. PART A: Patients receive ipilimumab intravenously (IV) over 90 minutes on day 1. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning day 1 of cycle 1, patients also receive ibrutinib orally (PO) once daily (QD) in the absence of disease progression or unacceptable toxicity. Patients who complete 4 doses of ipilimumab and are deriving benefit from it, without severe toxicities, may continue to receive ipilimumab every 12 weeks for up to a total of 2 years. PART B: Patients receive ipilimumab IV over 90 minutes and nivolumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning day 7 of cycle 1, patients also receive ibrutinib PO QD in the absence of disease progression or unacceptable toxicity. Patients who complete 4 doses of ipilimumab and nivolumab, and are deriving benefit from it, without severe toxicities, may continue to receive ipilimumab every 12 weeks and nivolumab every 4 weeks for up to a total of 2 years. After completion of study treatment, patients are followed up at 30 days, and then every 3 months thereafter.

Conditions

• Hematopoietic and Lymphoid Cell Neoplasm
• Recurrent Chronic Lymphocytic Leukemia
• Recurrent Small Lymphocytic Lymphoma
• Refractory Chronic Lymphocytic Leukemia
• Refractory Small Lymphocytic Lymphoma
• Richter Syndrome

Interventions

Type	Name	Description
DRUG	Ibrutinib	Given PO
BIOLOGICAL	Ipilimumab	Given IV
BIOLOGICAL	Nivolumab	Given IV

Timeline

• Start date: 2022-07-14
• Primary completion: 2025-02-21
• Completion: 2025-02-21
• First posted: 2021-03-04
• Last updated: 2025-02-28

Regulatory

• FDA-regulated drug study