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Chronic Lymphocytic LeukemiaPhase 2NCT05336812

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

A Phase 2 study testing Acalabrutinib, Obinutuzumab and Venetoclax in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Ohio State University Comprehensive Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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 . Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Acalabrutinib, Obinutuzumab and Venetoclax
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
1 siteUnited States
Study dates
13 Sep 2022to 31 Oct 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 27Show fewer
  • 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
  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
  • Adequate bone marrow independent of growth factor support or infusion support at screening unless evidence shows that the cytopenia(s) is due to marrow involvement by CLL/SLL and/or disease-related immune thrombocytopenia, or anemia. If cytopenias are due to disease in the bone marrow any degree of cytopenias are allowed. Patients with active uncontrolled autoimmune cytopenias are excluded
  • Absolute neutrophil count (ANC) >= 1000/mm^3
  • Platelets >= 30,000/mm^3
  • Hemoglobin >= 7 g/dL
  • Total bilirubin =< 2.0 x upper limit of normal (ULN) (excepting Gilbert's syndrome)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
  • Creatinine clearance >= 30 mL/min/1.73m^2
  • Using 24-hour creatinine clearance or modified Cockcroft-Gault equation
  • Woman of childbearing potential (WOCBP) who are sexually active must use highly effective methods of contraception during treatment and for at least 2 days after last acalabrutinib dose, 30 days after last venetoclax dose, and 6 months after last obinutuzumab dose
  • Willing and able to participate in all required evaluations and procedures in this study protocol
  • Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information

Who cannot join

  • 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
Show all 27Show fewer
  • 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
  • Patients with uncontrolled autoimmune disease requiring > 20 mg of daily prednisone or equivalent
  • Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening
  • Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists
  • Prothrombin time (PT)/international normalized ratio (INR) or activated partial thromboplastin time (aPTT) (in the absence of lupus anticoagulant) > 2 x ULN
  • History of significant cerebrovascular disease/event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study drug
  • Major surgical procedure within 28 days of 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
  • Hepatitis B or C serologic status:
  • Subjects who are hepatitis B core antibody (anti-HBc) positive and who are hepatitis B surface antigen (HBsAg) negative will need to have a negative polymerase chain reaction (PCR) and must be willing to undergo deoxyribonucleic acid (DNA) PCR testing during the study to be eligible. Those who are HBsAg positive or hepatitis B PCR positive will be excluded
  • Subjects who are hepatitis C antibody positive will need to have a negative PCR result to be eligible. Those who are hepatitis C PCR positive will be excluded
  • Breastfeeding or pregnant
  • Vaccination with live vaccines 28 days prior to registration for study screening
  • Concurrent participation in another therapeutic clinical trial

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

The Ohio State University Comprehensive Cancer Center contact

800-293-5066

OSUCCCClinicaltrials@osumc.edu

Megan Nussbaum contact

614-688-9309

megan.nussbaum@osumc.edu

United States1 site, 1 recruiting

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

    Kerry Rogers, MD, 614-293-3873, kerry.rogers@osumc.edu

    Adam S. Kittai, MD

    Recruiting

Other trials in United States

About this study

Official title: Prospective Randomized Phase II Study of Acalabrutinib + Obinutuzumab or Venetoclax in Previously Untreated CLL

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate whether the addition of venetoclax or obinutuzumab for 6 cycles to patients receiving acalabrutinib for 1 year in treatment-naive (TN) chronic lymphocytic leukemia (CLL) will improve rate of bone marrow (BM) undetectable minimal residual disease (uMRD).

SECONDARY OBJECTIVES:

  1. To assess the safety and tolerability of a delayed approach to combination therapy in patients with TN CLL.

II. To determine the overall response rate (ORR) of the addition of venetoclax or obinutuzumab for 6 cycles to patients receiving acalabrutinib for 1 year in TN CLL.

III. To determine the progression free survival (PFS) of the addition of venetoclax or obinutuzumab for 6 cycles to patients receiving acalabrutinib for 1 year in TN CLL.

IV. To determine the duration of response (DOR) of the addition of venetoclax or obinutuzumab for 6 cycles to patients receiving acalabrutinib for 1 year in TN CLL.

  1. To determine the time to next treatment (TTNT) of the addition of venetoclax or obinutuzumab for 6 cycles to patients receiving acalabrutinib for 1 year in TN CLL.

EXPLORATORY OBJECTIVES:

  1. To determine the concordance rate between uMRD status as measured by next generation sequencing (NGS) versus standard flow cytometry as well as blood vs bone marrow, and examine implications for PFS.

II. To determine how acalabrutinib plus venetoclax or obinutuzumab changes numbers of T, B, and natural killer (NK) cells during and after therapy.

III. To determine how baseline genomic features predict outcomes following acalabrutinib plus venetoclax or obinutuzumab.

OUTLINE: Patients are randomized into 1 of 2 arms.

ARM I: Patients receive acalabrutinib orally (PO) twice daily (BID) on days 1-28. Patients also receive obinutuzumab intravenously (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.

ARM II: Patients receive acalabrutinib PO BID on days 1-28. Patients also receive venetoclax PO once daily (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.

After completion of the study treatment, patients are followed up at 30 days and every 6 months up to 10 years.

Being tested
Acalabrutinib, Obinutuzumab, Venetoclax
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AcalabrutinibDrug

    Also called ACP-196, Bruton Tyrosine Kinase Inhibitor ACP-196, Calquence

    Given PO

  • ObinutuzumabBiological

    Also called Anti-CD20 Monoclonal Antibody R7159, GA-101, GA101, Gazyva

    Given IV

  • VenetoclaxDrug

    Also called ABT-0199, ABT-199, ABT199, GDC-0199

    Given PO

Study groups in NCT05336812
Study groupRoleWhat they receive
Arm I (acalabrutinib, obinutuzumab)ExperimentalPatients 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.
Receives: Drug: Acalabrutinib; Biological: Obinutuzumab
Arm II (acalabrutinib, venetoclax)ExperimentalPatients 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.
Receives: Drug: Acalabrutinib; Drug: Venetoclax

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 1 year

Secondary outcomes (5)

  1. Progression-free survival

    Will be calculated and compared between those who are uMRD by flow cytometry versus (vs) next generation sequencing (NGS) in the different treatment arms.

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

  2. Time to next treatment (TTNT)

    Will be estimated with 95% CIs for each arm.

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

  3. Overall response rate (ORR)

    ORR (computed tomography [CT] based) will be defined as the proportion of patients achieving a complete or partial response according to the International Workshop (iw)CLL criteria after combination therapy is completed; any eligible patient who begins treatment with the combination regimen will be included in the denominator when calculating the ORR. ORR will be reported with a 95% binomial exact confidence interval for each arm.

    Measured: Up to 1 year

  4. Duration of response (DOR)

    DOR will be estimated using Kaplan-Meier method. The median DOR and DOR at 3 years will be estimated with 95% confidence intervals (CIs) for each arm.

    Measured: 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

  5. Incidence of adverse events

    Will be summarized by type and severity according to Common Terminology Criteria for Adverse Events (CTCAE) version (v). 5.0, with a focus on grade 3 or higher adverse events. Adverse events (AEs), adverse events of special interests (AESIs), and serious adverse events (SAEs) that occur during acalabrutinib monotherapy will be summarized separately from those that occur with combination therapy.

    Measured: Up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Apr 2022
  2. Study start13 Sep 2022
  3. Primary completion31 Oct 2026 (estimated)
  4. Study completion31 Oct 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
52 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05336812
Sponsor's protocol ID
OSU-21193
Other IDs
NCI-2022-01752
Status last verified
Feb 2026
First submitted
16 Mar 2022
Last updated
19 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Acalabrutinib, Obinutuzumab and Venetoclax in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Ohio State University Comprehensive Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 19 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact The Ohio State University Comprehensive Cancer Center (800-293-5066, OSUCCCClinicaltrials@osumc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Up to 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05336812.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2026.

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