Acalabrutinib and Obinutuzumab for the Treatment of Chronic Lymphocytic Leukemia

NCT04505254 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2019-1141NCI-2020-05262
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial investigates the how well acalabrutinib and obinutuzumab work in treating patients with chronic lymphocytic leukemia (CLL). Acalabrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with obinutuzumab may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving acalabrutinib and obinutuzumab may help to control disease progression in CLL patients who have not received treatment for CLL.

Conditions

Small Lymphocytic Lymphoma; Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (3)

• Treatment-free remission

  Defined as the time from discontinuation of acalabrutinib to the date of CLL relapse with active disease.

  At 6 months after discontinuation of acalabrutinib, up to 4 years

• Overall response rate

  Defined as complete response

  After 6 cycles (each cycle 28 days) of treatment,up to 4 years

• Overall response rate

  Defined as partial response

  After 6 cycles (each cycle 28 days) of treatment,up to 4 years

Secondary Outcomes (3)

• Clinical factors associated with a treatment-free remission

  Up to 6 months after completion of treatment

• Treatment-free remission length

  Up to 6 months after completion of treatment

• Success rate of re-treatment in patients who relapse

  Up to 6 months after completion of treatment

Study Arms (1)

Treatment (acalabrutinib, obinutuzumab)

EXPERIMENTAL

Patients receive acalabrutinib PO BID every 12 hours starting on day 1 of cycle 1, and obinutuzumab IV over 4-6 hours on days 1 and 2 of cycle 3, and day 1 of cycles 4-8. Patients who do not achieve a complete response or remission after cycle 8 may receive single-agent acalabrutinib therapy PO BID for an additional 6 cycles at the discretion of their treating physician. Patients who are in partial response or who have stable disease receive an additional 6 cycles of acalabrutinib PO BID and obinutuzumab IV. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Acalabrutinib; Biological: Obinutuzumab

Interventions

Obinutuzumab BIOLOGICAL

Given IV

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

Treatment (acalabrutinib, obinutuzumab)

Acalabrutinib DRUG

Given PO

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

Treatment (acalabrutinib, obinutuzumab)

Eligibility Criteria

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

You may qualify if:

• Diagnosis CLL/small lymphocytic lymphoma (SLL) and be untreated
• Patients must have an indication for treatment by 2018 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Patients of childbearing potential must be willing to practice highly effective birth control during treatment and for 2 days after the last dose of acalabrutinib or 18 months after the last dose of obinutuzumab, whichever is later
• A negative urine pregnancy test (within 7 days of day 1) is required for women with childbearing potential
• Adequate renal and hepatic function as indicated by all of the following: Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) except for patients with bilirubin elevation due to Gilbert's disease who will be allowed to participate
• An alanine transferase (ALT) =\< 2.5 x ULN
• An estimated creatinine clearance (CrCl) of \> 30 mL/min, as calculated by the Cockcroft-Gault equation unless disease related
• Free of prior malignancies for 2 years with exception of patients diagnosed with basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast who are eligible even if they are currently treated or have been treated and/or diagnosed in the past 2 years prior to study enrollment. If patients had another malignancy of indolent behavior in the past 2 years prior to study enrollment that is expected to be cured with treatment they received such patients can be enrolled, after consultation with the principal investigator

You may not qualify if:

• Pregnant or breast-feeding females
• Prior CLL/SLL treatment
• Known history of infection with human immunodeficiency virus (HIV) or any uncontrolled active significant infection (eg, bacterial, viral or fungal)
• Signs of active hepatitis B or C. Subjects who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR). Those who are hepatitis B surface antigen (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. Those who are hepatitis C PCR positive will be excluded
• Patients with uncontrolled autoimmune hemolytic anemia (AIHA) or autoimmune thrombocytopenia (ITP)
• Patients with severe hematopoietic insufficiency as defined by an absolute neutrophil count of less than 500/μL, unless disease-related, and/or a platelet count of less than 30,000/μL at time of screening for this protocol.
• Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of heart failure, or any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification. Subjects with controlled, asymptomatic atrial fibrillation can enroll. Patients with a history of paroxysmal atrial fibrillation (PAF) or deep vein thrombosis or pulmonary embolism (DVT/PE) can be included if they had no signs of PAF or DVT/PE in the last 6 months before enrolment. Patients with ongoing atrial fibrillation (AFib) or ongoing PAF or DVT/PE should be excluded
• History of stroke or cerebral hemorrhage within 6 months
• Known history or evidence of bleeding diathesis or coagulopathy within 3 months
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
• Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to day 1. Bone marrow aspiration and/or biopsy are allowed
• Serious, non-healing wound, ulcer, or bone fracture
• Treatment with warfarin (Coumadin) or any other vitamin K antagonist. Patients who recently received warfarin must be off warfarin for at least 7 days prior to start of the study. Patients receiving novel oral anticoagulant (NOAC), also termed direct oral anticoagulant (DOAC) are permitted to enroll. Patients who are currently on a vitamin K antagonist must be switched to a non-vitamin K antagonist, such as a NOAC/DOAC
• Has difficulty with or is unable to swallow oral medication, or has significant gastrointestinal disease that would limit absorption of oral medication
• Known history of drug-specific hypersensitivity or anaphylaxis to study drug (including active product or excipient components)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

acalabrutinib; obinutuzumab

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

• Jan A Burger

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jan A Burger, MD

CONTACT

713-563-1487; jaburger@mdanderson.org

Study Design

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

Study Record Dates

• First Submitted: July 21, 2020
• First Posted: August 10, 2020
• Study Start: August 25, 2020
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: December 26, 2025

Record last verified: 2025-12

Locations

US (1)