Using venetoclax to treat CLL patients on BTK inhibitors

Study of the Efficacy and Safety of Venetoclax as Consolidation to Achieve Fix-Duration Treatment in CLL Patients Treated With BTK Inhibitor Monotherapy

This study is testing if adding venetoclax to the treatment of chronic lymphocytic leukemia (CLL) patients already on BTK inhibitors can help improve their condition after six months of treatment.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 79 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: The First Affiliated Hospital with Nanjing Medical University (other)
• Drugs / interventions: ibrutinib, zanubrutinib, orelabrutinib, acalabrutinib, chemotherapy, immunotherapy, prednisone
• Locations: 1 site (Nanjing, Jiangsu)
• Trial ID: NCT06958705 on ClinicalTrials.gov

What this trial studies

This open-label, multicenter phase 2 study investigates the efficacy and safety of venetoclax as a consolidation therapy for patients with chronic lymphocytic leukemia (CLL) who have been on BTK inhibitor monotherapy for at least six months. Eligible patients will receive a combination of a BTK inhibitor and venetoclax for 12 cycles after a standard dose ramp-up. The study aims to evaluate minimal residual disease (MRD) status in peripheral blood and bone marrow during and after treatment. Following the combination therapy, patients will discontinue both medications and be monitored for outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-80 with a diagnosis of CLL/SLL who have been on BTK inhibitor monotherapy for more than six months and show a response to treatment.

Not a fit: Patients who are not on BTK inhibitor monotherapy or those with severe comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes and prolong remission in CLL patients currently on BTK inhibitors.

How similar studies have performed: Other studies have shown promising results with similar consolidation therapies in CLL, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* 1\. Age: 18-80 years-old.
* 2\. Patients must have a diagnosis of CLL/SLL.
* 3\. Detectable MRD by flow cytometry (10\^-4 sensitivity) in the peripheral blood.
* 4\. Patients who are on BTK inhibitor monotherapy for more than 6 months. This study includes patients who are taking one of the following BTK inhibitors: ibrutinib, zanubrutinib, orelabrutinib, and acalabrutinib.
* 5\. Patients need to have a response of at least PR (CR/PR) to BTK inhibitor monotherapy.
* 6\. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
* 7\. Patients must have adequate renal and hepatic function:
* Serum bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for patients with Gilbert's disease;
* Serum creatinine clearance of ≥ 50 ml/min (calculated or measured);
* ALT and AST ≤ 3.0 × ULN, unless clearly due to disease involvement.
* 8\. Adequate bone marrow function:
* Platelet count of greater than 50,000/µl, with no platelet transfusion in prior 2 weeks;
* ANC ≥ 1000/µl in the absence of growth factor support unless due to compromised bone marrow production from CLL, indicated by ≥ 80% CLL in marrow;
* Hemoglobin ≥ 8g/dL.
* 9\. Adequate cardiac function, as assessed by:
* Absence of uncontrolled cardiac arrhythmia;
* Echocardiogram demonstrating LVEF ≥ 35%;
* NYHA functional class ≤ 2.
* 10\. Ability to provide informed consent and adhere to the required follow-up.

Exclusion Criteria:

* 1\. Richter transformation.
* 2\. Active malignancy requiring systemic therapy, other than CLL, with the exception of: adequately treated in situ carcinoma of the cervix uteri; adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin; previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
* 3\. Major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy, experimental therapy within 3 weeks prior to the first dose of the study drug.
* 4\. Grade 3 or 4 hemorrhage within the past 3 weeks.
* 5\. Uncontrolled active infections (viral, bacterial, and fungal).
* 6\. Females who are pregnant or lactating.
* 7\. Known HIV positive.
* 8\. Active hepatitis B infection (defined as the presence of detectable HBV DNA or HBe antigen). Patients who are HBsAg positive or HBcAb positive are eligible, provided HBV DNA is negative. These patients must have monthly monitoring of HBV DNA for the duration of the study.
* 9\. Active hepatitis C, defined by the detection of hepatitis C RNA in plasma by PCR.
* 10\. Active, uncontrolled autoimmune phenomenon (autoimmune hemolytic anemia or immune thrombocytopenia) requiring steroid therapy \> 20 mg prednisone daily or equivalent, within 7 days of starting venetoclax.
* 11\. Received other therapeutic agents for CLL/SLL during BTK inhibitor treatment prior to enrollment.
* 12\. Concurrent use of warfarin or equivalent vitamin K inhibitor or other oral anticoagulant treatment.
* 13\. Received strong CYP3A inhibitors or strong CYP3A inducers within 7 days of starting venetoclax.
* 14\. Consuming grapefruit, grapefruit products, Seville oranges, or star fruit within 7 days of starting venetoclax.
* 15\. Prior treatment with venetoclax or other Bcl-2 inhibitor.
* 16\. Malabsorption syndrome or other condition that precludes enteral route of administration.

Where this trial is running

Nanjing, Jiangsu

• Department of Haematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital — Nanjing, Jiangsu, China (RECRUITING)

Study contacts

• Study coordinator: Jianyong Li, PhD, MD

Conditions: Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma