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NCT03580928: AVO

Acalabrutinib, Venetoclax, and Obinutuzumab for Initial Therapy of CLL

Active, enrolled Phase 2 Results posted Last updated 13 February 2026
What this trial tests

Phase 2 trial testing Venetoclax in Chronic Lymphocytic Leukemia (CLL) in 72 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline
7 August 2018
Primary endpoint
10 April 2024
31 December 2027

Quick facts

Lead sponsorDana-Farber Cancer Institute
PhasePhase 2
StatusActive, enrolled
Study typeINTERVENTIONAL
Allocationnon randomized
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment72
Start date7 August 2018
Primary completion10 April 2024
Estimated completion31 December 2027
Sites4 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Dana-Farber Cancer Institute

Who can join

18 and older, any sex, with Chronic Lymphocytic Leukemia (CLL). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Rate of Bone Marrow (BM) Minimal Residual Disease (MRD) Negative Complete Response (CR) After 15 Cycles Primary · BM biopsy evaluated at baseline, cycle 4, 8, 16 on day 1. Relative to this endpoint is 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.

GroupValue95% CI
Acalabrutinib/Venetoclax/Obinutuzumab (AVO) With Non-high-risk CLL Disease0.3780.224 – 0.552
Acalabrutinib/Venetoclax/Obinutuzumab (AVO) With High-risk CLL Disease0.4570.283 – 0.638
Rate of Partial Response (PRR) After 15 Cycles Secondary · BM biopsy evaluated at baseline, cycle 4, 8, 16 on day 1. Relative to this endpoint is after 15 cycles

The PRR was defined as the proportion of participants achieving PR based on 2018 IW-CLL criteria.

GroupValue95% CI
Acalabrutinib/Venetoclax/Obinutuzumab (AVO) With Non-high-risk CLL Disease0.540.37 – 0.698
Acalabrutinib/Venetoclax/Obinutuzumab (AVO) With High-risk CLL Disease0.40.236 – 0.582
Rate of Complete Response ( Including With Incomplete Count Recovery (CRi)) Secondary · BM biopsy evaluated at baseline, cycle 4, 8, 16, 25 on day 1.

The CR+CRi rate was defined as the proportion of participants achieving CR+CRi based on 2018 IW-CLL criteria.

After cycle 8
GroupValue95% CI
Acalabrutinib/Venetoclax/Obinutuzumab (AVO) With Non-high-risk CLL Disease0.240.12 – 0.41
Acalabrutinib/Venetoclax/Obinutuzumab (AVO) With High-risk CLL Disease0.20.08 – 0.37
After cycle 16
GroupValue95% CI
Acalabrutinib/Venetoclax/Obinutuzumab (AVO) With Non-high-risk CLL Disease0.4320.267 – 0.609
Acalabrutinib/Venetoclax/Obinutuzumab (AVO) With High-risk CLL Disease0.510.336 – 0.689
After cycle 25
GroupValue95% CI
Acalabrutinib/Venetoclax/Obinutuzumab (AVO) With Non-high-risk CLL Disease0.460.29 – 0.63
Acalabrutinib/Venetoclax/Obinutuzumab (AVO) With High-risk CLL Disease0.620.44 – 0.79
Median Progression-Free Survival (PFS) Secondary · 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.

Progression-free survival based on the Kaplan-Meier method is defined as the duration between starting study therapy and documented disease progression (PD) or death, censored at time of last disease assessment.

GroupValue95% CI
Acalabrutinib/Venetoclax/Obinutuzumab (AVO) With Non-high-risk CLL DiseaseNANA – NA
Acalabrutinib/Venetoclax/Obinutuzumab (AVO) With High-risk CLL Disease49.3849.38 – NA
Median Overall Survival (OS) Secondary · Up to 2 years

Overall Survival (OS) based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.

GroupValue95% CI
Acalabrutinib/Venetoclax/Obinutuzumab (AVO) With Non-high-risk CLL DiseaseNANA – NA
Acalabrutinib/Venetoclax/Obinutuzumab (AVO) With High-risk CLL DiseaseNANA – NA
Rate of Peripheral Blood (PB) MRD Secondary · PB MRD evaluated on cycle 4, 8, 13, 16, 19, 22, 25, and every 3 cycles thereafter on day 1.

The rate of PB MRD was defined as the proportion of participants achieving negative MRD based on 2018 IW-CLL criteria. PB MRD evaluate by flow cytometry.

after 8 cycles
GroupValue95% CI
Acalabrutinib/Venetoclax/Obinutuzumab (AVO) With Non-high-risk CLL Disease0.680.5 – 0.82
Acalabrutinib/Venetoclax/Obinutuzumab (AVO) With High-risk CLL Disease0.690.51 – 0.83
after 16 cycles
GroupValue95% CI
Acalabrutinib/Venetoclax/Obinutuzumab (AVO) With Non-high-risk CLL Disease0.860.71 – 0.95
Acalabrutinib/Venetoclax/Obinutuzumab (AVO) With High-risk CLL Disease0.80.63 – 0.92
after 25 cycles
GroupValue95% CI
Acalabrutinib/Venetoclax/Obinutuzumab (AVO) With Non-high-risk CLL Disease0.890.75 – 0.97
Acalabrutinib/Venetoclax/Obinutuzumab (AVO) With High-risk CLL Disease0.690.5 – 0.84
Median Time to BM MRD-positive Disease Recurrence Secondary · Disease evaluated at baseline, cycle 4, 8, 16 on day 1.

Median Time to BM MRD-positive Disease Recurrence based on the Kaplan-Meier method, is defined as the duration from the date of achieving MRD-negative status in the bone marrow to the date of first documented MRD-positive recurrence in the bone marrow, or death, whichever occurs first.

GroupValue95% CI
Acalabrutinib/Venetoclax/Obinutuzumab (AVO) With Non-high-risk CLL DiseaseNANA – NA
Acalabrutinib/Venetoclax/Obinutuzumab (AVO) With High-risk CLL DiseaseNANA – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: AE collection thought entire study, on cycle 1 day 1, cycle 2 day 1, 2, 8, 15, 22, cycle 3 day 1 and 15, cycle 4 day 1, 2, 3, 8, 9, 15, 16, 22, 23, cycle 5 day 1 and 15, then day 1 on each cycle. Median duration of treatment is 25.56 months with range (0.56, 52.2).. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Acalabrutinib/Venetoclax/Obinutuzumab (AVO) With Non-high-risk CLL Disease
Serious: 10/37 (27%)
Deaths: 0/37
Acalabrutinib/Venetoclax/Obinutuzumab (AVO) With High-risk CLL Disease
Serious: 9/35 (26%)
Deaths: 3/35

Serious adverse events (15 terms)

ReactionSystemAcalabrutinib/Venetoclax/O…Acalabrutinib/Venetoclax/O…
Neutrophil count decreasedInvestigations
Lung infectionInfections and infestations
ColitisGastrointestinal disorders
Non-cardiac chest painGeneral disorders
Infections and infestations - Other, specifyInfections and infestations
Upper respiratory infectionInfections and infestations
Infusion related reactionInjury, poisoning and procedural complications
Injury, poisoning and procedural complications - Other, specifyInjury, poisoning and procedural complications
Cardiac troponin I increasedInvestigations
Platelet count decreasedInvestigations
HyperkalemiaMetabolism and nutrition disorders
Tumor lysis syndromeMetabolism and nutrition disorders
ArthritisMusculoskeletal and connective tissue disorders
Acute kidney injuryRenal and urinary disorders
Urinary tract obstructionRenal and urinary disorders
Other adverse events (206 terms — click to expand)

ReactionSystemAcalabrutinib/Venetoclax/O…Acalabrutinib/Venetoclax/O…
FatigueGeneral disorders
Neutrophil count decreasedInvestigations
Platelet count decreasedInvestigations
HeadacheNervous system disorders
BruisingInjury, poisoning and procedural complications
AnemiaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
HypocalcemiaMetabolism and nutrition disorders
DiarrheaGastrointestinal disorders
HypertensionVascular disorders
Upper respiratory infectionInfections and infestations
Rash maculo-papularSkin and subcutaneous tissue disorders
Gastroesophageal reflux diseaseGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
Creatinine increasedInvestigations
HypophosphatemiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
Alkaline phosphatase increasedInvestigations
HyponatremiaMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
Abdominal painGastrointestinal disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Nasal congestionRespiratory, thoracic and mediastinal disorders
HyperhidrosisSkin and subcutaneous tissue disorders
ConstipationGastrointestinal disorders
Edema limbsGeneral disorders
Infusion related reactionInjury, poisoning and procedural complications
Muscle crampMusculoskeletal and connective tissue disorders
CoughRespiratory, thoracic and mediastinal disorders
DyspepsiaGastrointestinal disorders
PainGeneral disorders
Aspartate aminotransferase increasedInvestigations
HyperglycemiaMetabolism and nutrition disorders
HyperuricemiaMetabolism and nutrition disorders
InsomniaPsychiatric disorders
PalpitationsCardiac disorders
FeverGeneral disorders
White blood cell decreasedInvestigations
AnorexiaMetabolism and nutrition disorders

Most-reported serious reactions: Neutrophil count decreased, Lung infection, Colitis, Non-cardiac chest pain, Infections and infestations - Other, specify, Upper respiratory infection, Infusion related reaction, Injury, poisoning and procedural complications - Other, specify.

Data from ClinicalTrials.gov NCT03580928 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Comparative Analysis of BTK Inhibitors and Mechanisms Underlying Adverse Effects.
    Estupiñán HY, Berglöf A, Zain R, Smith CIE. · · 2021 · cited 191× · PMID 33777941 · DOI 10.3389/fcell.2021.630942
  2. Small molecule inhibitors targeting the cancers.
    Liu GH, Chen T, Zhang X, Ma XL, et al · · 2022 · cited 127× · PMID 36254250 · DOI 10.1002/mco2.181
  3. BTK inhibitors in the treatment of hematological malignancies and inflammatory diseases: mechanisms and clinical studies.
    Alu A, Lei H, Han X, Wei Y, et al · · 2022 · cited 88× · PMID 36183125 · DOI 10.1186/s13045-022-01353-w
  4. Acalabrutinib, venetoclax, and obinutuzumab as frontline treatment for chronic lymphocytic leukaemia: a single-arm, open-label, phase 2 study.
    Davids MS, Lampson BL, Tyekucheva S, Wang Z, et al · · 2021 · cited 76× · PMID 34534514 · DOI 10.1016/s1470-2045(21)00455-1
  5. Current and future treatment strategies in chronic lymphocytic leukemia.
    Patel K, Pagel JM. · · 2021 · cited 60× · PMID 33902665 · DOI 10.1186/s13045-021-01054-w
  6. Combination strategies to overcome resistance to the BCL2 inhibitor venetoclax in hematologic malignancies.
    Yue X, Chen Q, He J. · · 2020 · cited 51× · PMID 33292251 · DOI 10.1186/s12935-020-01614-z
  7. Novel agents and regimens for hematological malignancies: recent updates from 2020 ASH annual meeting.
    Hou JZ, Ye JC, Pu JJ, Liu H, et al · · 2021 · cited 43× · PMID 33879198 · DOI 10.1186/s13045-021-01077-3
  8. Phase II Study of Acalabrutinib, Venetoclax, and Obinutuzumab in a Treatment-Naïve Chronic Lymphocytic Leukemia Population Enriched for High-Risk Disease.
    Davids MS, Ryan CE, Lampson BL, Ren Y, et al · · 2025 · cited 31× · PMID 39645236 · DOI 10.1200/jco-24-02503

Verify or expand the search:

Other trials of Venetoclax

Trials testing the same drug.

Other recruiting trials for Chronic Lymphocytic Leukemia (CLL)

Currently open trials in the same condition.

Other Dana-Farber Cancer Institute trials

Trials by the same sponsor.

Verify against primary sources

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing