Previously untreated Chronic Lymphocytic Leukemia Without del(17p) or TP53 Mutation MedDRA version: 20.0 Level: LLT Classification code 10009310 Term: CLL System Organ Class: 100000004864
Conditions
Sponsors
Acerta Pharma B.V.
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: 64 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.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 according to the IWCLL 2018 criteria. 2.Overall response rate (ORR), defined as the proportion of subjects with a complete response (CR), complete response with incomplete marrow recovery (CRi), or partial response (PR) per the investigator and IRC assessment as per IWCLL 2018 criteria 3.Duration of objective response (DOR), defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause per the investigator and IRC assessment as per IWCLL 2018 criteria 4.Time to next Therapy (TTNT), defined as the time from randomization to institution of non-protocol specified treatment for chronic lymphocytic leukemia (CLL) 5.Minimal residual disease (MRD) negativity rate (determined as the proportion of subjects with MRD-negativity) measured in the peripheral blood by flow cytometry (10-4) 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) 6.Overall survival (OS), defined as the time from randomization to death from any cause ;Timepoint(s) of evaluation of this end point: 64 months | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Czech Republic, Denmark, France, Germany, Hungary, Israel, Italy, Korea, Democratic People's Republic of, Netherlands, New Zealand, Poland, Saudi Arabia, South Africa, Spain, Sweden, Taiwan, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactCheng Quah, Medical Director
Acerta Pharma B.V.
Outcome results
None listed