Intermittent Versus Continuous Venetoclax With Acalabrutinib for CLL/SLL
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorZulfa Omer
About this trial
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)
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
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.
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.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Venetoclax
Drugintermittent venetoclax (7days administration per cycle) + acalabrutinib
Acalabrutinib
Drugintermittent venetoclax (7days administration per cycle) + acalabrutinib
Venetoclax
Drugcontinuous venetoclax (28 days administrations per cycle) + acalabrutinib
Acalabrutinib
Drugcontinuous venetoclax (28 days administrations per cycle) + acalabrutinib
Treatment groups
62 Participants
are divided into 2 treatment groupsGroup A: Arm A: intermittent venetoclaxExperimental treatment 2 interventions
Group B: Arm B: continuous venetoclaxExperimental treatment 2 interventions
Trial outcomes
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.
Time frame
Post 12 cycles of treatment (each cycle is 28 days)Secondary outcomes
1
Circulating numbers of NK cells measured by flow cytometry
Circulating numbers of NK cells using flow cytometry in both treatment arms at pretreatment, C1, C4, C6, C9, C12 and 3 months after completion of treatment.
Time frame
Pretreatment, Cycle1, Cycle4, Cycle6, Cycle9, Cycle12 and 3 months after completion of treatment (each cycle is 28 days)2
Circulating numbers of T cells measured by flow cytometry
Circulating numbers of T cells using flow cytometry in both treatment arms at pretreatment, C1, C4, C6, C9, C12 and 3 months after completion of treatment.
Time frame
Pretreatment, Cycle1, Cycle4, Cycle6, Cycle9, Cycle12 and 3 months after completion of treatment (each cycle is 28 days)3
Overall Survival -defined as time from study randomization to death or last follow up
Overall Survival (OS) defined as time from study randomization to death or last follow up
Time frame
From date of patient baseline visit to death or last follow up (up to 5 years post treatment).4
Progression Free Survival (PFS) defined as the time from study randomization to disease progression, death, or last follow up after treatment
Progression Free Survival (PFS) defined as the time from study randomization to disease progression, death, or last follow up after treatment with acalabrutinib in combination with intermittent or continuous venetoclax in patients with untreated CLL/SLL.
Time frame
From date of patient baseline visit to death or last follow up (up to 5 years post treatment).Other outcomes
1
BAX clonal hematopoiesis using NGS
BAX clonal hematopoiesis using NGS at Cycle 12, 3 and 5 years post treatment
Time frame
Cycle 12, 3 and 5 years post treatment (each cycle is 28 days)2
Development of Secondary cancer
Secondary cancer development at 3- and 5-years post treatment
Time frame
3- and 5-years post treatment3
Quality of life measured by EORTC QLQ-CLL17 survey
Quality of life measures in the intermittent and continuous venetoclax treatment groups at baseline (prior to first dose), cycle 1, cycle 6, cycle 9 and end of cycle 12.
Time frame
Baseline (prior to first dose), cycle 1, cycle 6, cycle 9 and end of cycle 12 (each cycle is 28 days)4
Mechanism of toxicity
Mechanism of toxicity to this combination at baseline (pre-treatment) and at C1, 4, 6, 9, and C12
Time frame
Baseline (pre-treatment) and at cycle 1,cycle 4, cycle 6, cycle 9, and cycle 12 (each cycle is 28 days)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Zulfa Omer
Lead sponsor
University of Cincinnati
Sponsor institution
Source ClinicalTrials.gov