A Study on Limiting Treatment Time With Acalabrutinib Combined With Obinutuzumab in People With CLL or SLL

NCT04722172 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 20-503
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 8

Brief Summary

This study will test the safety of limiting treatment time with acalabrutinib and obinutuzumab in people who have chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The researchers want to find out whether stopping the study drugs when the cancer responds to the treatment, followed by a period of observation in which no treatment is given, is better than, the same as, or worse than the usual approach. A usual treatment for CLL and SLL is to give the study drugs continuously until the cancer progresses, even if the disease is in remission. But when people receive these drugs for long periods of time, they can have serious side effects and their cancer can become resistant to treatment.

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Keywords

Acalabrutinib; Obinutuzumab; 20-503

Outcome Measures

Primary Outcomes (1)

• progression-free survival (PFS)

  Progression free survival (PFS) will be measured from the time the patient initiates treatment, until documented progression of disease, relapse, or death due to any cause, whichever comes first.

  36 months

Secondary Outcomes (1)

• Adverse events from Acalabrutinib with Obinutuzumab

  3 years

Study Arms (1)

Acalabrutinib Combined With Obinutuzumab

EXPERIMENTAL

Patients will receive acalabrutinib for a minimum of 13 cycles and maximum 26 cycles and Obinutuzumab will be administered during Cycles 2-7. This will be followed by treatment-free observation through the 65th cycle. Patients who progress during the observation period, per iwCLL criteria, will receive 13 cycles of acalabrutinib in combination with obinutuzumab in the retreatment phase of this study.

Drug: Acalabrutinib; Drug: Obinutuzumab

Interventions

Acalabrutinib DRUG

Acalabrutinib for a minimum of 13 cycles and maximum 26 cycles.

Acalabrutinib Combined With Obinutuzumab

Obinutuzumab DRUG

Obinutuzumab will be administered during Cycles 2-7.

Acalabrutinib Combined With Obinutuzumab

Eligibility Criteria

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

You may qualify if:

• Signed informed consent form (ICF). Legally Authorized Representatives are permitted.
• Ability and willingness to comply with requirements of the study protocol
• ≥ 18 years-old
• Have documented previously untreated CLL or SLL per WHO criteria and require treatment per iwCLL guidelines
• ECOG performance status of 0, 1, or 2, with no deterioration over the previous 2 weeks prior to baseline or day of first dosing
• Participants must have adequate organ and marrow function as defined below:
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN), unless there is a disease involvement of the liver, hemolysis, or a known history of Gilbert's disease.
• Hemoglobin ≥ 8 g/dL without transfusion support, unless anemia is due to marrow involvement of CLL.
• Absolute neutrophil count (ANC) ≥ 1.0 x 10\^9/L.
• AST and ALT ≤ 2.5 times the ULN.
• Creatinine clearance (CrCl) \> 30 mL/min as calculated using modified Cockcroft- Gault or MDRD Formula
• PT/INR ≤ 2 times the ULN and aPTT ≤ 2 times the ULN unless the elevation in PT/INR or aPTT is solely attributable to direct oral anticoagulant.
• Platelet count without transfusion support must be ≥ 50,000 cells/mm3 or ≥ 30,000 cells/mm\^3 in subjects with documented bone marrow involvement, as determined locally.
• For women of childbearing potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use a highly effective contraceptive method (failure rate of \< 1%) per year during the treatment period and for at least 18 months after the last dose of study medication. Women of childbearing potential must have a negative serum pregnancy test result within 3 days prior to initiation of study drug
• Women must refrain from donating eggs during this same period

You may not qualify if:

• Prior CLL-directed therapy
• °Excluding corticosteroid therapy started for non-CLL related reasons or brief courses for disease related symptom management
• Received any investigational drug within 30 days or 5 half-lives (whichever is shorter) before 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 that have been curatively treated by surgery and/or radiation therapy from which subject is disease-free for ≥3 years without further treatment.
• Transformation of CLL to aggressive lymphoma (Richter's transformation to NHL or Hodgkin's lymphoma, or pro-lymphocytic leukemia)
• CLL with deletion of chromosome 17p and/or TP53 mutation. Patients must have FISH or array CGH analysis and NGS for TP53 mutations locally as per SOC within 60 days of C1D1 (peripheral blood, bone marrow or lymph node with disease involvement are acceptable sources) as SOC.
• History of or ongoing confirmed central nervous system (CNS) lymphoma.
• Known hypersensitivity to any active ingredient in the study drugs.
• Active bleeding, or presence of known bleeding disorder (e.g. von Willebrand's disease) or hemophilia.
• Any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• Clinically significant cardiac disease that includes symptomatic arrhythmia (subjects with controlled, asymptomatic atrial fibrillation or other atrial arrhythmias during screening are allowed to enroll on study)
• Intracranial hemorrhage, stroke within 6 months of study enrollment
• Symptomatic, or history of documented congestive heart failure (NY Heart Symptomatic, or history of documented congestive heart failure (NY Heart Association functional classification III-IV

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• AstraZeneca: collaborator
• Genentech, Inc.: collaborator

Study Sites (8)

Memorial Sloan Kettering Basking Ridge (All protocol activities)

Basking Ridge, New Jersey, 07920, United States

Location

Hackensack Meridian Health (Data collection only)

Hackensack, New Jersey, 07601, United States

Location

Memorial Sloan Kettering Monmouth (All protocol activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (All protocol activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack (All protocol activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (All protocol activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (All protocol activities)

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering 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

• Meghan Thompson, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: This is a phase II, multicenter clinical trial.

Study Record Dates

• First Submitted: January 20, 2021
• First Posted: January 25, 2021
• Study Start: May 21, 2021
• Primary Completion: February 1, 2026
• Study Completion: February 1, 2026
• Last Updated: August 27, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

US (8)