Duvelisib for Ibrutinib-Resistant Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
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|ClinicalTrials.gov Identifier: NCT04209621|
Recruitment Status : Recruiting
First Posted : December 24, 2019
Last Update Posted : July 2, 2020
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.
To test how people with ibrutinib-resistant CLL respond to duvelisib.
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
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 participant s whole lymph node or part of it will be removed through the skin.
- Optional lymphapheresis. For this, the participant s 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.
|Condition or disease||Intervention/treatment||Phase|
|Small Lymphocytic Leukemia (SLL) Chronic Lymphocytic Leukemia (CLL)||Drug: Duvelisib Drug: Ibrutinib||Phase 2|
- 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 zeta 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.
-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 iwCLL guidelines
- Patients with known Richter transformation will be excluded.
- 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 six28-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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Duvelisib for Ibrutinib-Resistant Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)|
|Estimated Study Start Date :||July 7, 2020|
|Estimated Primary Completion Date :||June 1, 2023|
|Estimated Study Completion Date :||June 1, 2025|
single-arm, open-label phase 2 study with a safety lead-in cohort
twice daily as tolerated until disease progression
daily for the first six 28-day cycles
- Overall response rate (ORR) [ Time Frame: 3 months ]Overall response rate (ORR) after six cycles (3 cycles of duvelisib plus ibrutinib followed by 3 cycles of duvelisib alone) including complete and partial remission with modification for treatment-related lymphocytosis
- Progression-free survival, Overall survival,Duration of response, Best response, Safety [ Time Frame: Ongoing ]Progression-free survival (time from treatment initiation to progression of disease or death from any cause); Overall survival (time from treatment initiation to death from any cause); Duration of response (time from initial response to progression of disease); Best response; -Safety of duvelisib plus ibrutinib combination; Safety of duvelisib monotherapy
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04209621
|Contact: Pia Nierman, R.N.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Clare C Sun, M.D.||National Heart, Lung, and Blood Institute (NHLBI)|