Acalabrutinib in Combination With Venetoclax or Obinutuzumab for the Treatment of Treatment-naive Chronic Lymphocytic Leukemia

NCT05336812 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: OSU-21193NCI-2022-01752
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests whether acalabrutinib in combination with venetoclax or obinutuzumab works to shrink tumors in patients with treatment-naive chronic lymphocytic leukemia . Acalabrutinib is also an inhibitor that works in the body to block the activation of certain cells that lead to the growth of cancerous B cells. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Obinutuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving acalabrutinib in combination with venetoclax or obinutuzumab may help ease symptoms, decrease the amount of cancer suggestive of improvement, prolonged disease-free remission and/or survival, and increased knowledge about cancer treatment in patients with chronic lymphocytic leukemia. Patients will be treated with acalabrutinib for 12 cycles, and then randomized to receive 6 cycles of acalabrutinib plus obinutuzumab or acalabrutinib plus venetoclax.

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (1)

• Rate of bone marrow undetectable minimal residual disease (uMRD), defined as tumor cell in 10,000 cells using standard flow based assay, achieved after completion of therapy

  Will provide uMRD rates at the end of treatment with combination therapy for each experimental arm with 95% confidence intervals.

  Up to 1 year

Secondary Outcomes (5)

• Progression-free survival

  From the start of combination therapy until documented disease progression, or death from any cause, whichever occurs first, assessed up to 1 year

• Time to next treatment (TTNT)

  At 1 and 3 years up to time from start of combination therapy until next treatment is initiated

• Overall response rate (ORR)

  Up to 1 year

• Duration of response (DOR)

  Time from the first tumor assessment supports the response, at 1 and 3 years, or to the time of confirmed disease progression or death due to any cause

• Incidence of adverse events

  Up to 1 year

Other Outcomes (3)

• Discordant rate of uMRD between flow cytometry and NGS

  At various time points up to 1 years

• Numbers of T, B, and NK cells during and after therapy

  Up to 1 year

• Presence or absence of genomic features

  Up to 1 year

Study Arms (2)

Arm I (acalabrutinib, obinutuzumab)

EXPERIMENTAL

Patients receive acalabrutinib PO BID on days 1-28. Patients also receive obinutuzumab IV on days 1, 2, 8, and 15 of cycle 13 and day 1 of cycles 14-18. Treatment repeats every 28 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Acalabrutinib; Biological: Obinutuzumab

Arm II (acalabrutinib, venetoclax)

EXPERIMENTAL

Patients receive acalabrutinib PO BID on days 1-28. Patients also receive venetoclax PO QD on days 1-28 days of cycles 13-18. Treatment repeats every 28 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Acalabrutinib; Drug: Venetoclax

Interventions

Acalabrutinib DRUG

Given PO

Also known as: ACP-196, Bruton Tyrosine Kinase Inhibitor ACP-196, Calquence

Arm I (acalabrutinib, obinutuzumab); Arm II (acalabrutinib, venetoclax)

Obinutuzumab BIOLOGICAL

Given IV

Also known as: Anti-CD20 Monoclonal Antibody R7159, GA-101, GA101, Gazyva, huMAB(CD20), R7159, RO 5072759, RO-5072759, RO5072759

Arm I (acalabrutinib, obinutuzumab)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Arm II (acalabrutinib, venetoclax)

Eligibility Criteria

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

You may qualify if:

• Men and women \>= 18 years of age
• Diagnosis of CLL/small lymphocytic lymphoma (SLL) meeting criteria established in the 2018 International Workshop (iw)CLL guidelines
• Must be treatment-naive: Received no prior chemotherapy, immunotherapy, or targeted therapy for the treatment of CLL, with the exceptions of palliative loco-regional radiotherapy, rituximab for autoimmune conditions, or corticosteroids for symptoms control
• Patients must meet criteria for treatment as defined by 2018 iwCLL guidelines which includes at least one of the following criteria:
• Evidence of marrow failure as manifested by the development or worsening of anemia or thrombocytopenia (not attributable to autoimmune hemolytic anemia or thrombocytopenia)
• Massive (\>= 6 cm below the costal margin), progressive or symptomatic splenomegaly
• Massive nodes (\>= 10 cm) or progressive or symptomatic lymphadenopathy
• Progressive lymphocytosis with a lymphocyte doubling time \< 6 months or an increase of \>= 50% over a 2 month period
• Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy
• Symptomatic or functional extranodal involvement (e.g. skin, kidney, lung, spine)
• Constitutional symptoms, which include any of the following:
• Unintentional weight loss of 10% or more within 6 months
• Significant fatigue
• Fevers \> 100.5 degrees Fahrenheit (F) for 2 weeks or more without evidence of infection
• Night sweats \>= 1 month without evidence of infection

You may not qualify if:

• Patients with high-risk disease as defined by:
• Presence of deletion 17p13 on cytogenetic analysis by fluorescent in situ hybridization (FISH)
• Presence of TP53 mutation on next generation sequencing
• Presence of complex karyotype on cytogenetic evaluation
• Defined as \>= 3 karyotypic abnormalities
• Treatment with a moderate or strong CYP3A inhibitor or inducer within 7 days prior to first dose of acalabrutinib or venetoclax or need for treatment with a strong CYP3A inhibitor or inducer during the period or the study. Patients who have a need for treatment with a moderate CYP3A inhibitor or inducer during acalabrutinib or venetoclax dose escalation will also be excluded
• Known active involvement of the central nervous system by lymphoma or leukemia
• Subject with other malignancies that are associated with a life expectancy of \< 2 years or that would confound assessment of toxicity in this study
• Clinically significant cardiovascular disease such as symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification. Note: Subjects with controlled atrial fibrillation can enroll on study
• Is unable to swallow oral medication, or has significant gastrointestinal disease that would limit absorption of oral medication
• Known history of infection with human immunodeficiency virus (HIV)
• Subjects with active infections requiring intravenous (IV) antibiotic/antiviral therapy are not eligible for entry onto the study until resolution of the infection. Subjects on prophylactic antibiotics or antivirals are acceptable
• Known history of hypersensitivity or anaphylaxis to study drug(s) including active product or excipient components
• Active bleeding or history of bleeding diathesis (e.g., hemophilia or von Willebrand disease)
• Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP) unrelated to underlying CLL

Sponsors & Collaborators

• Ohio State University Comprehensive Cancer Center: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Related Links

• The Jamesline

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

acalabrutinib; obinutuzumab; 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

Study Officials

• Kerry S Rogers, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

The Ohio State University Comprehensive Cancer Center

CONTACT

800-293-5066; OSUCCCClinicaltrials@osumc.edu

Megan Nussbaum

CONTACT

614-688-9309; megan.nussbaum@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 16, 2022
• First Posted: April 20, 2022
• Study Start: September 13, 2022
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)