A Randomized Phase II Study Of Bruton Tyrosine Kinase Inhibitor With Or Without Venetoclax In Veterans With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

Summary

People who have chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) are often treated with ibrutinib, acalabrutinib, or zanubrutinib. These are pills that are taken by mouth. This type of pill is called "Bruton Tyrosine Kinase Inhibitor" or BTKi. Another treatment for CLL/SLL is a different pill called venetoclax. The purpose of this study is to compare continuing the current treatment with BTKi alone, as long as it is working, to another arm of treatment which adds venetoclax to the current treatment (BTKi), for one year. After one year, both pills in this arm of treatment would be stopped and the participants will be closely monitored.

Eligibility

Inclusion Criteria:

* CLL or SLL diagnosis
* Patients must have been diagnosed with CLL (\> 5000 B-cells per uL of peripheral blood at any point during the course of their disease) or small lymphocytic lymphoma (SLL) with \<5000 B-cells per µL of blood but with disease-associated lymphadenopathy by 2018 IWCLL criteria.
* Prior treatment
* Patients must be currently receiving CLL/SLL directed therapy with a BTKi (i.e., ibrutinib, acalabrutinib, zanubrutinib) for at least six months.
* The dose of BTKi must be stable for at least the past three months.
* Age 18 years
* ECOG performance status 0-2
* Detectable or measurable CLL/SLL in blood or imaging during the screening period.

Detectable CLL/SLL in the blood is defined either by elevation in absolute lymphocyte count or by diagnostic flow cytometry from blood demonstrating presence of CLL cells.

* Low TLS risk, defined as having all lymph nodes less than 5 cm in diameter (radiographically) and absolute lymphocyte count less than 25 x 109/L in blood, within 30 days of enrollment.
* Required initial laboratory values
* Absolute Neutrophil Count (ANC) 1,000/mm3 except if due to bone marrow involvement
* Platelet Count (untransfused) 30,000/mm3 except if due to bone marrow involvement
* Calc. Creatinine Clearance 40 mL/min (by Cockcroft-Gault)
* Bilirubin 1.5 x upper limit of normal (ULN) except if due to liver involvement, hemolysis, or Gilbert's disease
* AST / ALT 2.5 x upper limit of normal (ULN) except if due to liver involvement
* Other
* Patients must be able to swallow oral medications and not have the following conditions: disease significantly affecting gastrointestinal absorption, resection of the stomach or small bowel, partial or complete bowel obstruction.
* Patients must be able to receive either a xanthine oxidase inhibitor or rasburicase

Exclusion Criteria:

* Prior treatment
* Patients must not have progression of CLL/SLL on BTKi therapy prior to initiation of the study therapy.
* Patients must not have received the combination of BTKi + venetoclax previously.
* Comorbid conditions or other active diseases
* Patients must not have any history of Richter's transformation or prolymphocytic leukemia.
* If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable and be on suppressive therapy, if indicated.
* Please note: IVIG can cause a false positive hepatitis B serology. If patients receiving routine IVIG have core antibody or surface antigen positivity without evidence of active viremia (negative hepatitis B DNA) they may still participate in the study, must have hepatitis serologies and hepatitis B DNA monitored periodically by the treating physician.
* If history of hepatitis C virus (HCV) infection, must be treated with undetectable HCV viral load.
* Patients with Class III or Class IV heart failure by New York Heart Association, those with unstable angina, and those with uncontrolled arrhythmia are not eligible.
* Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy are eligible for this trial.
* Concomitant medications
* Patients must not be receiving active systemic anticoagulation with heparin or warfarin. Patients on warfarin must discontinue the drug for at least 10 days prior to registration on the study.
* Chronic concomitant treatment with strong inhibitors of CYP3A4/5 is not recommended on this study. Patients on strong CYP3A inhibitors must discontinue the drug for 14 days prior to registration on the study or discuss with the study principal investigator.
* Chronic concomitant treatment with strong CYP3A4/5 inducers is not recommended. Patients must discontinue the drug 14 days prior to registration on the study or discuss with the study principal investigator.
* Patients must not require more than 20 mg prednisone or equivalent corticosteroid daily.
* Patients must not have uncontrolled active systemic infection requiring intravenous antibiotics

Conditions3

Locations4 sites

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