This study is being done to test the effectiveness and safety of an investigational drug called acalabrutinib (ACP-196) when taken with already marketed drugs called Venetoclax and Obinutzumab in comparison to chemotherapy that is already in wide use for treatment of patients who have chronic lymphocytic leukemia and who have never been treated before.

A Randomized, Multicenter, Open-Label, Phase 3 Study to Compare the Efficacy and Safety of Acalabrutinib (ACP-196) in Combination with Venetoclax with and without Obinutuzumab Compared to Investigator’s Choice of Chemoimmunotherapy in Subjects with Previously Untreated Chronic Lymphocytic Leukemia Without del(17p) or TP53 Mutation - Not available at this time

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2018-002443-28-HU

Enrollment

780

Registered

2019-04-02

Start date

2019-06-04

Completion date

Unknown

Last updated

2025-02-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Previously untreated Chronic Lymphocytic Leukemia Without del(17p) or TP53 Mutation MedDRA version: 21.0 Level: LLT Classification code 10009310 Term: CLL System Organ Class: 100000004864

Interventions

Product Name: acalabrutinib Product Code: ACP-196 Pharmaceutical Form: Capsule, hard INN or Proposed INN: ACALABRUTINIB CAS Number: 1420477-60-6 Current Sponsor code: ACP-196 Concentration unit: mg mi

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Men and women =18 years of age. 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0–2. 3. Diagnosis of CLL that meets published diagnostic criteria (Hallek et al. 2018): Monoclonal B-cells (either kappa or lambda light chain restricted) that are clonally co-expressing B-cell marker (CD19, CD20, and CD23) and CD5. Prolymphocytes may comprise =65 years) yes F.1.3.1 Number of subjects for this age range 500

Exclusion criteria

Exclusion criteria: •Any prior CLL-specific therapies (except corticosteroid treatment administered due to necessary immediate intervention; within the last 10 days before start of study treatment, only dose equivalents up to 20 mg prednisone daily are permitted). •Detected del(17p) or TP53 mutation. •Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL) (e.g., Richter’s transformation, PLL, or diffuse large B cell lymphoma [DLBCL]), or central nervous system (CNS) involvement by leukemia. •Any comorbidity or organ system impairment rated with a single CIRS score of 4 (excluding the eyes/ears/nose/throat/larynx organ system), or a total CIRS score of >6. •Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura. •History of confirmed progressive multifocal leukoencephalopathy (PML). •Received any investigational drug within 30 days 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, except for the following: •Curatively treated basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or carcinoma in situ of the prostate at any time prior to study. •Other cancers not specified above which have been curatively treated by surgery and/or radiation therapy from which subject is disease-free for =3 years without further treatment.

Design outcomes

Primary

Measure	Time frame
Main Objective: To evaluate the efficacy of acalabrutinib/venetoclax (AV; Arm A) compared with chemoimmunotherapy (fludarabine/cyclophosphamide/rituximab [FCR]/ bendamustine/rituximab [BR]; Arm C) ;Secondary Objective: To evaluate the efficacy of acalabrutinib/venetoclax/obinutuzumab (AVG; Arm B) versus FCR/BR (Arm C) To evaluate the efficacy of AV (Arm A) versus FCR/BR (Arm C) and AVG (Arm B) versus FCR/BR (Arm C) ;Primary end point(s): Progression-free survival (PFS), defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the Independent Review Committee (IRC) according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 criteria.;Timepoint(s) of evaluation of this end point: Interim analysis: 42 months after the first subject is randomized Final analysis: 64 months after the first subject is randomized	—

Measure

Time frame

Main Objective: To evaluate the efficacy of acalabrutinib/venetoclax (AV; Arm A) compared with chemoimmunotherapy (fludarabine/cyclophosphamide/rituximab [FCR]/ bendamustine/rituximab [BR]; Arm C) ;Secondary Objective: To evaluate the efficacy of acalabrutinib/venetoclax/obinutuzumab (AVG; Arm B) versus FCR/BR (Arm C) To evaluate the efficacy of AV (Arm A) versus FCR/BR (Arm C) and AVG (Arm B) versus FCR/BR (Arm C) ;Primary end point(s): Progression-free survival (PFS), defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the Independent Review Committee (IRC) according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 criteria.;Timepoint(s) of evaluation of this end point: Interim analysis: 42 months after the first subject is randomized Final analysis: 64 months after the first subject is randomized

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Secondary

Measure	Time frame
Secondary end point(s): 1.Progression-free survival (PFS), defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the IRC assessment and investigator assessment, respectively. 2. Event-free survival (EFS), defined as the time from randomization to the first occurrence of disease progression, initiation of subsequent anti-CLL therapy, or death from any cause per IRC assessment and the investigator assessment, respectively. 3.Objective response rate (ORR), defined as the proportion of subjects with a CR, CRi, or PR per the investigator or and IRC assessment, respectively as per IWCLL 2018 criteria at or before initiation of subsequent anticancer therapy. 4.Duration of objective response (DOR), defined as the time from the first documentation of objective response to the earlier time of disease progression (assessed by the investigator and IRC, respectively, per IWCLL 2018 criteria) or death from any cause. 5.Time to next treatment (TTNT), defined as the time from randomization to institution of non-protocol specified treatment for chronic lymphocytic leukemia (CLL). 6.Overall survival (OS), defined as the time from randomization to death from any cause. 7.Minimal residual disease (MRD) negativity rate (determined as the proportion of subjects with MRD-negativity) measured in the peripheral blood by flow cytometry at the start of Cycle 9 (in Arm A), the start of Cycle 10 (in Arm B), and 12 weeks after the start of Cycle 6 (in Arm C).;Timepoint(s) of evaluation of this end point: Interim analysis: 42 months after the first subject is randomized Final analysis: 64 months after the first subject is randomized	—

Measure

Time frame

Secondary end point(s): 1.Progression-free survival (PFS), defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the IRC assessment and investigator assessment, respectively. 2. Event-free survival (EFS), defined as the time from randomization to the first occurrence of disease progression, initiation of subsequent anti-CLL therapy, or death from any cause per IRC assessment and the investigator assessment, respectively. 3.Objective response rate (ORR), defined as the proportion of subjects with a CR, CRi, or PR per the investigator or and IRC assessment, respectively as per IWCLL 2018 criteria at or before initiation of subsequent anticancer therapy. 4.Duration of objective response (DOR), defined as the time from the first documentation of objective response to the earlier time of disease progression (assessed by the investigator and IRC, respectively, per IWCLL 2018 criteria) or death from any cause. 5.Time to next treatment (TTNT), defined as the time from randomization to institution of non-protocol specified treatment for chronic lymphocytic leukemia (CLL). 6.Overall survival (OS), defined as the time from randomization to death from any cause. 7.Minimal residual disease (MRD) negativity rate (determined as the proportion of subjects with MRD-negativity) measured in the peripheral blood by flow cytometry at the start of Cycle 9 (in Arm A), the start of Cycle 10 (in Arm B), and 12 weeks after the start of Cycle 6 (in Arm C).;Timepoint(s) of evaluation of this end point: Interim analysis: 42 months after the first subject is randomized Final analysis: 64 months after the first subject is randomized

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Countries

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Czech Republic, Denmark, France, Germany, Hungary, Israel, Italy, Korea, Republic of, Netherlands, Poland, Russian Federation, Saudi Arabia, Slovakia, South Africa, Spain, Sweden, Taiwan, Turkey, Ukraine, United Kingdom, United States

Contacts

Public ContactClinical Trial Call Center

Acerta Pharma B.V.

acertamc@dlss.com18882929613

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026