Acalabrutinib, Venetoclax, and Obinutuzumab for Initial Therapy of CLL
AVO
A Phase 2 Study of Acalabrutinib, Venetoclax, and Obinutuzumab (AVO) for Initial Therapy of Chronic Lymphocytic Leukemia
2 other identifiers
interventional
72
1 country
4
Brief Summary
This research study is evaluating the combination of three drugs - acalabrutinib, venetoclax, and obinutuzumab -- as a possible treatment for chronic lymphocytic leukemia (CLL). The drugs involved in this study are:
- Acalabrutinib
- Venetoclax
- Obinutuzmab
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Aug 2018
Longer than P75 for phase_2
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 25, 2018
CompletedFirst Posted
Study publicly available on registry
July 10, 2018
CompletedStudy Start
First participant enrolled
August 7, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 10, 2024
CompletedResults Posted
Study results publicly available
August 12, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2027
ExpectedFebruary 13, 2026
January 1, 2026
5.7 years
June 25, 2018
April 10, 2025
January 27, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Rate of Bone Marrow (BM) Minimal Residual Disease (MRD) Negative Complete Response (CR) After 15 Cycles
The rate of BM MRD was defined as the proportion of participants achieving CR and negative MRD based on 2018 IW-CLL criteria.
BM biopsy evaluated at baseline, cycle 4, 8, 16 on day 1. Relative to this endpoint is after 15 cycles
Secondary Outcomes (6)
Rate of Partial Response (PRR) After 15 Cycles
BM biopsy evaluated at baseline, cycle 4, 8, 16 on day 1. Relative to this endpoint is after 15 cycles
Rate of Complete Response ( Including With Incomplete Count Recovery (CRi))
BM biopsy evaluated at baseline, cycle 4, 8, 16, 25 on day 1.
Median Progression-Free Survival (PFS)
Disease evaluated at baseline, cycle 4, 8, 16 on day 1, and every 3 months thereafter. Median follow-up for all patients was 55.23 months.
Median Overall Survival (OS)
Up to 2 years
Rate of Peripheral Blood (PB) MRD
PB MRD evaluated on cycle 4, 8, 13, 16, 19, 22, 25, and every 3 cycles thereafter on day 1.
- +1 more secondary outcomes
Study Arms (2)
Acalabrutinib/Venetoclax/Obinutuzumab (AVO) with non-high-risk CLL disease
EXPERIMENTAL* Acalabrutinib will be administered orally twice daily at 100 mg bid * Venetoclax will be administered orally once daily, with dose ramp-up from 20 mg up to a final dose of 400 mg * Obinutuzumab will be administered as per standard of care for 6 months with dosing at 100 mg on cycle 1 day 1, 900 mg on cycle 1 day 2, and then 1,000 mg on cycle 1 days 8, 15, and day 1 of cycles 2-6
Acalabrutinib/Venetoclax/Obinutuzumab (AVO) with high-risk CLL disease
EXPERIMENTAL* Acalabrutinib will be administered orally twice daily at 100 mg bid * Venetoclax will be administered orally once daily, with dose ramp-up from 20 mg up to a final dose of 400 mg * Obinutuzumab will be administered as per standard of care for 6 months with dosing at 100 mg on cycle 1 day 1, 900 mg on cycle 1 day 2, and then 1,000 mg on cycle 1 days 8, 15, and day 1 of cycles 2-6. High-risk CLL disease (cohort 2), defined as 17p deletion and/or TP53 mutation
Interventions
Venetoclax is an oral drug that blocks the function of a protein called BCL-2. CLL cancer cells are thought to depend on the BCL-2 protein for their survival. By blocking BCL-2, venetoclax may kill cancer cells or stop them from growing.
Obinutuzumab is a type of drug called a monoclonal antibody. It targets a protein CD20 on the surface of the CLL cell, causing it to die
Acalabrutinib is a type of drug called a kinase inhibitor. It blocks a type of protein called Bruton Tyrosine Kinase (BTK) that helps CLL cells live and grow
Eligibility Criteria
You may qualify if:
- Subjects must have CLL or SLL
- In cohort 2, subjects must have TP53-aberrant disease defined as:
- Del(17p) detected on karyotype and/or FISH; OR
- TP53 mutation
- Participants must have measurable disease (lymphocytosis \> 5,000 / µl, or palpable or CT measurable lymphadenopathy ≥ 1.5 cm, or bone marrow involvement ≥30%).
- Subjects must not have received any prior systemic therapy for CLL or SLL due to meeting IWCLL 2018 guidelines and must currently have an indication for treatment as defined by the IWCLL 2018 guidelines:
- Massive or progressive or symptomatic splenomegaly; OR
- Massive lymph nodes, nodal clusters, or progressive lymphadenopathy; OR
- Significant fatigue (i.e. ECOG PS 2 or worse; cannot work or unable to perform usual activities); OR
- Fever ≥ 100.5°F for 2 or more weeks without evidence of infection; OR
- Night sweats for ≥ 1 months without evidence of infection; OR
- Presence of weight loss ≥ 10% over the preceding 6 months; OR
- Progressive lymphocytosis with an increase of ≥ 50% over a 2-month period or lymphocyte doubling time of less than 6 months; OR
- Evidence of progressive marrow failure as manifested by the development of or worsening of anemia and/or thrombocytopenia; OR
- Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids and another standard therapy such as rituximab; OR
- +11 more criteria
You may not qualify if:
- Participants who have a history of other malignancies except:
- Malignancy treated with curative intent and with no known active disease present and felt to be at low risk for recurrence by treating physician. Current adjuvant hormonal therapy for disease treated with curative intent is permissible.
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
- Adequately treated carcinoma in situ without evidence of disease.
- Low-risk prostate cancer on active surveillance
- Participants who are receiving any other investigational agents.
- History of severe allergic reactions attributed to compounds of similar chemical or biologic composition to obinutuzumab, venetoclax, or acalabrutinib. Patients with reactions to other CD20 monoclonal antibodies (e.g. rituximab, ofatumumab) are not excluded.
- Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV), and herpes zoster (VZV) at start of treatment
- Known or suspected Richter's transformation or known CNS involvement
- Concurrent systemic immunosuppressant therapy (e.g., cyclosporine A, tacrolimus, etc., within 28 days of the first dose of study drug or chronic administration of \>20 mg/day of prednisone within 7 days of the first dose)
- Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
- Ongoing or recent infection requiring intravenous antimicrobials at time of screening.
- Known bleeding disorders (e.g. von Willebrand's disease) or hemophilia.
- Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening.
- History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
- +11 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecacollaborator
- Dana-Farber Cancer Institutelead
- National Cancer Institute (NCI)collaborator
- National Institutes of Health (NIH)collaborator
- Genentech, Inc.collaborator
Study Sites (4)
Stamford Hospital/Bennett Cancer Center
Stamford, Connecticut, 06904, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Lifespan Cancer Institute
Providence, Rhode Island, 02903, United States
Related Publications (2)
Davids MS, Ryan CE, Lampson BL, Ren Y, Tyekucheva S, Fernandes SM, Crombie JL, Kim AI, Weinstock M, Montegaard J, Walker HA, Greenman C, Patterson V, Jacobson CA, LaCasce AS, Armand P, Fisher DC, Lo S, Olszewski AJ, Arnason JE, Ahn IE, Brown JR. Phase II Study of Acalabrutinib, Venetoclax, and Obinutuzumab in a Treatment-Naive Chronic Lymphocytic Leukemia Population Enriched for High-Risk Disease. J Clin Oncol. 2025 Mar;43(7):788-799. doi: 10.1200/JCO-24-02503. Epub 2024 Dec 7.
PMID: 39645236DERIVEDDavids MS, Lampson BL, Tyekucheva S, Wang Z, Lowney JC, Pazienza S, Montegaard J, Patterson V, Weinstock M, Crombie JL, Ng SY, Kim AI, Jacobson CA, LaCasce AS, Armand P, Arnason JE, Fisher DC, Brown JR. Acalabrutinib, venetoclax, and obinutuzumab as frontline treatment for chronic lymphocytic leukaemia: a single-arm, open-label, phase 2 study. Lancet Oncol. 2021 Oct;22(10):1391-1402. doi: 10.1016/S1470-2045(21)00455-1. Epub 2021 Sep 14.
PMID: 34534514DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Matthew Davids, MD
- Organization
- Dana-Farber Cancer Institute
Study Officials
- PRINCIPAL INVESTIGATOR
Matthew S. Davids, MD, MMSc
Dana-Farber Cancer Institute
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
June 25, 2018
First Posted
July 10, 2018
Study Start
August 7, 2018
Primary Completion
April 10, 2024
Study Completion (Estimated)
December 31, 2027
Last Updated
February 13, 2026
Results First Posted
August 12, 2025
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will not share