Duvelisib for Ibrutinib-Resistant Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Chronic Lymphocytic Leukemia (CLL) Clinical Trial

Official title: Duvelisib for Ibrutinib-Resistant Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

Status Terminated

Clinical Trial Summary

Background:

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are cancers often treated with the drug ibrutinib. For some people, ibrutinib stops working. Researchers want to see if adding another drug can help.

Objective:

To test how people with ibrutinib-resistant CLL respond to duvelisib.

Eligibility:

People ages 18 and older with CLL or SLL that is no longer responding to ibrutinib or has developed mutations that could stop it from working

Design:

Participants will be screened with:

• Medical history

• Physical exam

• Heart tests

• Blood and urine tests

• CT scan. For this, participants will have a dye injected into a vein. They will lie in a machine that takes pictures of the body.

• Bone marrow biopsy. For this, a needle injected into the participant s bone will remove marrow.

• Optional lymph node biopsy. For this, the participants whole lymph node or part of it will be removed through the skin.

• Optional lymphapheresis. For this, the participants blood is removed through a vein in one arm, the white blood cells separated out, and the blood returned through a vein in the other arm.

Participants will take duvelisib twice daily by mouth. They will continue ibrutinib at their current dose for the first 6 months. They will continue to take duvelisib until their CLL/SLL stops responding or they develop intolerable side effects.

Participants will take an antibiotic and antiviral medication. They may take steroids.

Participants will have blood tests every 2 weeks during the first 2 months.

Participants will have monthly follow-up visits during the first 6 months and every 3 months thereafter. These will include repeats of some of the screening tests.

Clinical Trial Description

Background:

• In chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), ibrutinib resistance is predominantly caused by somatic mutations in BTK and PLCG2. Virtually all patients with detectable mutations eventually develop progressive disease. Patients who discontinue ibrutinib often have rapidly progressive disease that can be difficult to control. These observations suggest that BTK inhibitors still exert at least a partial anti-tumor effect. Outcomes after ibrutinib discontinuation are poor. Early detection of BTK and PLCG2 mutations represents an opportunity for preemptive intervention to eliminate the resistant clone.

• Duvelisib is a dual PI3K-gamma and delta inhibitor. Duvelisib monotherapy improved progression-free survival and overall response rate compared to ofatumumab and had a manageable safety profile in subjects with previously treated CLL/SLL. Based on these results, duvelisib received US approval for CLL/SLL after at least 2 prior therapies.

• This study will assess duvelisib in patients who develop disease progression or BTK and/or PLCG2 mutations on ibrutinib. Duvelisib will overlap with ibrutinib for the first six 28-day cycles to prevent disease acceleration often seen in patients who discontinue ibrutinib.

Primary Objective:

-To investigate the rate of overall response to duvelisib in patients with ibrutinib-resistant CLL.

Key Eligibility Criteria:

• Patients on current treatment for CLL/SLL with ibrutinib and at least one of the following:

• BTK and/or PLCG2 mutations

• Progressive CLL per CLL guidelines

• Patients with known Richter transformation will be excluded.

Design:

• This is a single-center, single-arm, open-label phase 2 study with a safety lead-in cohort.

• Treatment plan: Duvelisib will be administered with ibrutinib for the first six 28-day cycles then duvelisib monotherapy will be administered continuously until disease progression or intolerance.

Study Duration: 5 years.

Participant Duration: until disease progression or intolerance. ;

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia (CLL)
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Small Lymphocytic Leukemia (SLL)

• NCT number: NCT04209621
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Terminated
• Phase: Phase 2
• Start date: July 31, 2020
• Completion date: January 22, 2021