Intermittent Versus Continuous Venetoclax With Acalabrutinib for CLL/SLL

NCT07014917 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: UCCC-HEM-23-01
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized Phase II study of intermittent versus continuous venetoclax therapy with Acalabrutinib in previously untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; CLL Variant

Keywords

Venetoclax; Acalabrutinib; CLL; SLL

Outcome Measures

Primary Outcomes (1)

• Complete Remission defined by the IWCLL 2018 criteria

  Complete Remission (CR) as defined by the IWCLL 2018 criteria after 12 cycles of treatment with acalabrutinib in combination with intermittent or continuous venetoclax in patients with untreated CLL/SLL.

  Post 12 cycles of treatment (each cycle is 28 days)

Secondary Outcomes (7)

• Circulating numbers of NK cells measured by flow cytometry

  Pretreatment, Cycle1, Cycle4, Cycle6, Cycle9, Cycle12 and 3 months after completion of treatment (each cycle is 28 days)

• Circulating numbers of T cells measured by flow cytometry

  Pretreatment, Cycle1, Cycle4, Cycle6, Cycle9, Cycle12 and 3 months after completion of treatment (each cycle is 28 days)

• Overall Survival -defined as time from study randomization to death or last follow up

  From date of patient baseline visit to death or last follow up (up to 5 years post treatment).

• Progression Free Survival (PFS) defined as the time from study randomization to disease progression, death, or last follow up after treatment

  From date of patient baseline visit to death or last follow up (up to 5 years post treatment).

• uMRD Complete Remission (CR) defined by negative luekemia cell to 10-6 using NGS Clonoseq

  Post 12 cycles of treatment (each cycle is 28 days)

Other Outcomes (7)

• BAX clonal hematopoiesis using NGS

  Cycle 12, 3 and 5 years post treatment (each cycle is 28 days)

• Development of Secondary cancer

  3- and 5-years post treatment

• Quality of life measured by EORTC QLQ-CLL17 survey

  Baseline (prior to first dose), cycle 1, cycle 6, cycle 9 and end of cycle 12 (each cycle is 28 days)

Study Arms (2)

Arm A: intermittent venetoclax

EXPERIMENTAL

intermittent venetoclax (7days administration per cycle) + acalabrutinib

Drug: Venetoclax; Drug: Acalabrutinib

Arm B: continuous venetoclax

EXPERIMENTAL

continuous venetoclax (28 days administrations per cycle) + acalabrutinib

Drug: Venetoclax; Drug: Acalabrutinib

Interventions

Venetoclax DRUG

intermittent venetoclax (7days administration per cycle) + acalabrutinib

Arm A: intermittent venetoclax

Acalabrutinib DRUG

intermittent venetoclax (7days administration per cycle) + acalabrutinib

Arm A: intermittent venetoclax

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Leukemia (SLL) as defined by the IWCLL including variation of flow cytometry, provided cytogenetic or mutational data are supportive of CLL/SLL diagnosis that requires therapy by one IWCLL criteria; and, must be previously untreated CLL/SLL.
• a. Note: Variation in flow cytometry is defined as patients who have atypical immunophenotyping for CLL (CD5 negative, CD23 negative or surface expression of CD79b that is bright) but clinically behave like CLL (leukocytosis, lymphadenopathy and splenomegaly) and have the FISH/Cytogenetics translocations (del 13q, trisomy 12, Del11q) or genomic features (XPO1, NOTCH1, SF3B1, FBXW7, MYD88, BIRC3, TRAF3, NFKBIE, SAMHD1, POT1, HIST1H1E, CHD2, ZMYM3, EGR2 and others) that are suggestive of CLL
• Men and Women ≥18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.
• Subjects must have adequate organ and marrow function as defined below:
• ANC ≥1,000/mcL, unless if neutropenia is due to extensive underlying CLL bone marrow disease then platelet threshold will be ANC ≥500/mcL unless WBC is \> to 50 x 109/L. If WBC is \> to 50 x 109/L there will be no lower threshold of ANC. Use of steroids for disease control is allowed.
• Platelets ≥30,000/mcL unless thrombocytopenia is due to extensive underlying CLL bone marrow disease platelets threshold will be ≥ 10, 000/mcl. Use of steroids for disease control is allowed.
• Total bilirubin ≤1.5 x ULN unless directly attributable to Gilbert's syndrome
• AST and ALT ≤3 × ULN
• Creatinine clearance (Cockcroft) ≥30 mL/min/1.73 m2 • CrCl by Cockcroft and Gault method: CrCl (mL/min) = (140 - age \[years\]) × weight (kg) × (F)a (72 × serum creatinine mg/dL a where F = 0.85 for females and F = 1 for males ≥ 30 mL/minute
• Female subjects who are sexually active and can bear children must agree to use highly effective forms of contraception while on the study and for 2 days after the last dose of acalabrutinib.
• Male subjects who are sexually active must agree to use highly effective forms of contraception with the addition of a barrier method (condom) during the study.
• Men must agree to refrain from sperm donation during the study.
• Willing and able to participate in all required evaluations and procedures in this study protocol, including swallowing tablets without difficulty.
• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local patient privacy regulations).

You may not qualify if:

• Evidence of any active concurrent disease (such as severe or uncontrolled systemic diseases that, in the investigator's opinion, make it undesirable for the patient to participate in the study or that would jeopardize compliance with the protocol.
• Patients with active Richter's transformation.
• History of or ongoing confirmed central nervous system (CNS) lymphoma.
• Received any investigational drug within 30 days or 5 half-lives (whichever is shorter) before first dose of study drug.
• Major surgical procedure within 30 days before the first dose of study drug. Note: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug.
• History of prior malignancy that could affect compliance with the protocol or interpretation of results in the opinion of the investigator, except for the following:
• Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin, carcinoma in situ of the cervix, breast or prostate at any time prior to study that are adequately treated. Patients with cancer not requiring therapy (ex: early prostate cancer under observation, should be discussed with Study PI).
• Continuation of maintenance therapy in patients with adequately treated malignancy
• Other cancers not specified above that have been curatively treated by surgery and/or radiation therapy and/or chemotherapy from which subject is disease-free for ≥3 years without further treatment
• Significant cardiovascular disease such as symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification at Screening.
• a. Note: Subjects with controlled, asymptomatic atrial fibrillation are allowed to enroll on study.
• Patients with a condition that would preclude adequate absorption, distribution, metabolism, or excretion of study treatment. For example, refractory nausea and vomiting, inability to swallow the formulated product, or malabsorption syndrome; chronic gastrointestinal disease gastric restrictions, or bariatric surgery such as gastric bypass; partial or complete bowel obstruction, or previous significant bowel resection.
• Received a live virus vaccination within 28 days of first dose of study drug.
• Uncontrolled HIV infection.
• History of or ongoing confirmed progressive multifocal leukoencephalopathy (PML).

Sponsors & Collaborators

• Zulfa Omer: lead

Study Sites (1)

University of Cincinnati

Cincinnati, Ohio, 45219, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

venetoclax; acalabrutinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Zulfa Omer

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

Central Study Contacts

UCCC Clinical Trials Office

CONTACT

513-584-7698; cancer@uchealth.com

Zulfa Omer, MD

CONTACT

cancer@uchealth.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Two-arm, open label Subjects will be randomized with 2:1 ratio into Arm A which will receive intermittent venetoclax (7days administration per cycle) + acalabrutinib and Arm B which will receive continuous venetoclax (28 days administrations per cycle) + acalabrutinib.

Study Record Dates

• First Submitted: May 5, 2025
• First Posted: June 11, 2025
• Study Start: December 5, 2025
• Primary Completion (Estimated): June 5, 2028
• Study Completion (Estimated): June 5, 2032
• Last Updated: January 6, 2026

Record last verified: 2026-01

Locations

US (1)