Acalabrutinib With or Without Obinutuzumab in Treating Patients With Early-Stage Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

NCT03516617 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: MC168ENCI-2018-0059117-008161
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 3

Brief Summary

This phase II trials studies how well acalabrutinib with or without obinutuzumab works in treating patients with early-stage chronic lymphocytic leukemia or small lymphocytic lymphoma. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as obinutuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving acalabrutinib with or without obinutuzumab will work better in treating patients with early-stage chronic lymphocytic leukemia or small lymphocytic lymphoma.

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (2)

• Rate of minimal residual disease (MRD)-negative complete response (Arm A and Arm B)

  Defined as an objective status of complete response (CR) or CR with incomplete marrow recovery (CRi) along with MRD negativity in the bone marrow by flow cytometry. Will be compared between the two arms. The proportion of successes will be estimated in each arm by the number of successes divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated in each arm based on the normal approximation. Comparison of MRD-negative complete response rates between the two treatment groups will be performed using a one-sided z-test (based on normal approximation with pooled variance of standardized test statistics) at significance level 0.10.

  After 12 cycles (cycle 1-6 = 28 days, cycles 7 and beyond = 84 days)

• Time to first therapy (TFT) in patients (Arm C)

  Defined as the time from the date of registration to the date of initiation of treatment for CLL.

  After 12 cycles (one cycle = 6 months)

Secondary Outcomes (7)

• Overall response rate (Arms A and B)

  Up to 10 years

• Progression-free survival (Arms A and B)

  From randomization up to 10 years

• Time to next therapy (Arms A and B)

  From the date of randomization up to 10 years

• Overall survival (Arms A and B)

  From randomization up to 10 years

• Progression-free survival (Arm C)

  From randomization up to 10 years

Other Outcomes (5)

• Quality of life

  Up to 10 years

• T-cells, natural killer (NK)-cells, and NK-T cells

  Baseline

• Bone marrow hematopoiesis (Arms A and B)

  Up to 10 years

Study Arms (3)

Arm A (acalabrutinib)

EXPERIMENTAL

Patients receive acalabrutinib PO BID on days 1-28. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive acalabrutinib PO BID on days 1-84. Treatment repeats every 84 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue treatment with acalabrutinib If MRD negative CR/CRi is not achieved after 12 cycles.

Drug: Acalabrutinib; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment

Arm B (acalabrutinib, obinutuzumab)

EXPERIMENTAL

Patients receive acalabrutinib PO BID on days 1-28 and obinutuzumab IV on days 1, 2, 8, and 15 of cycle 1 and days 1 of subsequent cycles. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive acalabrutinib PO BID on days 1-84. Treatment repeats every 84 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue treatment with acalabrutinib If MRD negative CR/CRi is not achieved after 12 cycles.

Drug: Acalabrutinib; Other: Laboratory Biomarker Analysis; Biological: Obinutuzumab; Other: Quality-of-Life Assessment

Arm C (observation)

ACTIVE COMPARATOR

Patients will be observed every 6 months for up to 2 years.

Other: Laboratory Biomarker Analysis; Other: Patient Observation; Other: Quality-of-Life Assessment

Interventions

Acalabrutinib DRUG

Given PO

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

Arm A (acalabrutinib); Arm B (acalabrutinib, obinutuzumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm A (acalabrutinib); Arm B (acalabrutinib, obinutuzumab); Arm C (observation)

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 B (acalabrutinib, obinutuzumab)

Patient Observation OTHER

Undergo observation

Also known as: Active Surveillance, deferred therapy, expectant management, Observation, Watchful Waiting

Arm C (observation)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm A (acalabrutinib); Arm B (acalabrutinib, obinutuzumab); Arm C (observation)

Eligibility Criteria

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

You may qualify if:

• Age \>= 18 years
• Diagnosis of:
• Biopsy-proven small lymphocytic lymphoma (SLL) , or
• Diagnosis of chronic lymphocytic leukemia (CLL) with a clonal B-cell population in the peripheral blood with immunophenotyping consistent with CLL as follows:
• The population of lymphocytes share both B-cell antigens (CD19, CD20 \[typically dim expression\], or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc.)
• Clonality as evidenced by kappa or lambda light chain expression (typically dim immunoglobulin expression) or other genetic method (e.g. IGHV analysis)
• Before diagnosing CLL or SLL, mantle cell lymphoma must be excluded by demonstrating a negative fluorescence in situ hybridization (FISH) analysis for t(11;14)(IgH/CCND1)
• Patients must be previously untreated
• Note: Prior chemotherapy or monoclonal antibody based therapy for treatment of CLL or SLL will be considered prior therapy; nutraceutical treatments with no established benefit in CLL (such as epigallocatechin gallate or EGCG, found in green tea or other herbal treatments or supplemental vitamins) will not be considered "prior treatment"; prior corticosteroid therapy for an indication other than CLL/SLL will not be considered "prior treatment"
• All patients will undergo testing for prognostic factors according to the CLL-IPI (testing obtained =\< 730 days prior to registration)
• Note: If the results for any of the prognostic factors included in the CLL-IPI are unknown including IGVH mutation status results not being available due to a failed laboratory assay, the patient is not eligible
• Note: When determining CLL-IPI, use most recent test results, if more than one result is available
• Note: Patients with CLL-IPI risk category of high risk or very high risk (total score of 4-10) will be randomized to Arms A or B
• Note: Patients with CLL-IPI risk category of low risk or intermediate risk (total score of 0-3) will be registered to Arm C
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2

You may not qualify if:

• Date of CLL/SLL diagnosis \>= 24 months prior to registration
• Prior exposure to ibrutinib or to a BCR inhibitor (e.g. Btk or PI3 kinase or Syk inhibitors) or a BCL-2 inhibitor (e.g. venetoclax)
• Known central nervous system (CNS) lymphoma or leukemia
• Patients with any of the following indications for chemotherapy:
• Evidence of progressive marrow failure as manifested by the development of or worsening anemia (=\< 11 g/dL) and/or thrombocytopenia (=\< 100 x 10\^9/L) not due to autoimmune disease
• Symptomatic or progressive lymphadenopathy, splenomegaly or hepatomegaly
• One or more of the following disease-related symptoms:
• Weight loss \>= 10% within the previous 6 months
• Extreme fatigue attributed to CLL
• Fevers \>= 100.4 degrees Fahrenheit (F) for 2 weeks without evidence of infection
• Drenching night sweats without evidence of infection
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy; NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (3)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

RECRUITING

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

RECRUITING

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

acalabrutinib; obinutuzumab; Watchful Waiting; Observation

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

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration; Methods; Investigative Techniques

Study Officials

• Sameer A. Parikh, M.D.

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trials Referral Office

CONTACT

855-776-0015; mayocliniccancerstudies@mayo.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2018
• First Posted: May 4, 2018
• Study Start: September 10, 2018
• Primary Completion (Estimated): March 15, 2027
• Study Completion (Estimated): October 16, 2030
• Last Updated: February 9, 2026

Record last verified: 2026-02

Locations

US (3)