Phase 2 Study of Disease Risk Mutation-Guided Finite Acalabrutinib+Venetoclax for Relapsed CLL Post-1L Finite cBTKi+BCL2i ± Obinutuzumab

NCT07024706 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: D8220C00036
• Study Type: interventional
• Target: 80
• Locations: 7 countries
• Sites: 29

Brief Summary

This study will evaluate the efficacy and safety of finite-duration acalabrutinib plus venetoclax therapy in patients with relapsed CLL or SLL, and have previously responded to first line (1L) cBTKi + BCL2i therapy (± obinutuzumab) and maintained a response for at least two years post-treatment.

Conditions

Chronic Lymphocytic Leukemia (CLL); Small Lymphocytic Lymphoma (SLL)

Keywords

Chronic Lymphocytic Leukemia (CLL); Small Lymphocytic Lymphoma (SLL); Relapsed CLL; Refractory CLL; Acalabrutinib

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  ORR, defined as the proportion of participants who achieve best response of CR, CRi, nPR, or PR per iwCLL criteria as assessed by the investigator.

  ORR assessed at multiple timepoints during treatment period (each cycle is 28 days). Timepoint for primary analysis is at completion of cycle 14

Secondary Outcomes (7)

• Progression Free Survival (PFS)

  PFS will be assessed from Cycle 3 to Cycle 24 during treatment period (each cycle is 28 days)

• Duration of Response (DoR)

  DoR will be assessed from Cycle 3 to Cycle 24 during treatment period (each cycle is 28 days)

• Event Free Survival (EFS)

  EFS will be assessed from Cycle 3 to Cycle 24 during treatment period (each cycle is 28 days)

• Time to Next Treatment (TTNT)

  TTNT will be assessed from Cycle 3 to Cycle 24 during treatment period (each cycle is 28 days)

• Overall Survival (OS)

  OS will be assessed every 3 months through the study completion, for 5 years

Study Arms (1)

Acalabrutinib and Venetoclax

EXPERIMENTAL

For Cohort 1, each participant will be in the study for approximately 5 years (60 months) counting from C1D1, starting with 2 cycles of acalabrutinib lead-in treatment, followed by 12 cycles of AV combination treatment, and 4 years of follow-up. For Cohort 2, each participant will be in the study for approximately 5 years (60 months) counting from C1D1 starting with 2 cycles of acalabrutinib lead-in treatment, followed by 22 cycles of AV combination treatment, and 3 years of follow-up.

Drug: Acalabrutinib; Drug: Venetoclax

Interventions

Acalabrutinib DRUG

Acalabrutinib is an orally available cBTKi that inhibits the activity of BTK and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway.

Also known as: CALQUENCE®

Acalabrutinib and Venetoclax

Venetoclax DRUG

Venetoclax is an orally bioavailable inhibitor of the anti-apoptotic protein BCL-2

Also known as: Venclexta®, Venclyxto®

Acalabrutinib and Venetoclax

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be ≥ 18 years at the time of signing informed consent.
• Diagnosis of CLL/SLL according to iwCLL guidelines 2018 (Hallek et al. 2018)
• Participants must have received first line treatment with fixed duration covalent BTKi plus BCL2i therapy (± obinutuzumab) with a response ≥ PR (i.e., CR, CRi, nPR, or PR) with a minimum of 2 years since the end of the prior 1L treatment.
• The following data must be available or at least the appropriate samples drawn/acquired prior to dosing:
• IGHV (mutated vs. unmutated)
• del(17p) (present or absent)
• TP53 mutation (present or absent)
• ECOG performance status 0, 1 or 2
• Adequate organ and bone marrow (BM) function.

You may not qualify if:

• Any evidence of diseases that, in the investigator's opinion, makes it undesirable for patient to participate in the study.
• Significant cardiovascular or cerebrovascular disease.
• Active bleeding or history of bleeding diathesis (e.g., hemophilia or von Willebrand disease).
• Child-Pugh B/C liver cirrhosis.
• History of prior or current malignancy.
• HIV positive
• History of progressive multifocal leukoencephalopathy (PML).
• Active hepatitis B or C infection:
• Corticosteroid use \> 20 mg within 1 week before the first dose of study intervention.
• History of hypersensitivity or anaphylaxis to study intervention(s).
• Requires treatment with a strong CYP3A4 inhibitor/inducer.
• Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists.
• Major surgical procedure within 30 days of the first dose of study intervention.

Sponsors & Collaborators

• Genentech, Inc.: collaborator
• AstraZeneca: lead
• AbbVie: collaborator

Study Sites (29)

Research Site

Boston, Massachusetts, 02215, United States

Location

Research Site

Charlotte, North Carolina, 28204, United States

Location

Research Site

Durham, North Carolina, 27705, United States

Location

Research Site

Horn, 3580, Austria

Location

Research Site

Brno, 625 00, Czechia

Location

Research Site

Hradec Kralova, 50005, Czechia

Location

Research Site

Ostrava, 708 502, Czechia

Location

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Dublin, 7, Ireland

Location

Research Site

Dublin, D08 NHY1, Ireland

Location

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Lugo, 48022, Italy

Location

Research Site

Meldola, 47014, Italy

Location

Research Site

Milan, 20162, Italy

Location

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Padua, 35128, Italy

Location

Research Site

Roma, 00165, Italy

Location

Research Site

Rome, 00168, Italy

Location

Research Site

Torino, 10126, Italy

Location

Research Site

Bydgoszcz, 85-168, Poland

Location

Research Site

Krakow, 30-727, Poland

Location

Research Site

Lodz, 93-513, Poland

Location

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Lublin, 20-090, Poland

Location

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Warsaw, 02-172, Poland

Location

Research Site

Warsaw, 02-776, Poland

Location

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Barcelona, 08041, Spain

Location

Research Site

Barcelona, 8035, Spain

Location

Research Site

Granada, 18014, Spain

Location

Research Site

Madrid, 28031, Spain

Location

Research Site

Madrid, 28034, Spain

Location

Research Site

Madrid, 28041, Spain

Location

Research Site

Majadahonda, 28222, Spain

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

acalabrutinib; venetoclax

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

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479; information.center@astrazeneca.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2025
• First Posted: June 17, 2025
• Study Start: January 30, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 15, 2029
• Last Updated: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

AU (1); US (3); PL (6); CZ (3); ES (7); IE (2); IT (7)