A Single Arm Study of Acalabrutinib Conbimed With Obinutuzumab in Chinese Patients With Previously Untreated CLL

NCT05950997 | Recruiting

• 1 other identifier: ESR-22-22033
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, prospective study to assess the efficacy and safety of acalabrutinib combined with obinutuzumab in subjects with previously untreated chronic lymphocytic leukemia.

Conditions

Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Progression-free survival rate at 24 months

  24-month progression-free survival rate is defined as the proportion of subjects without progression or death due to any cause at 24 months since the start of study drug. The evaluation of progression will be investigator-assessed per International Workshop on Chronic Lymphocytic Leukemia criteria(iwCLL2018) criteria.

  At 24 months

Secondary Outcomes (5)

• Objective response rate (ORR)

  24 months after LPI

• Duration of response (DOR)

  At 24 months

• 24-month overall survival rate (24m OS rate)

  At 24 months

• Adverse Events (AEs)

  Up to acalabrutinib treatment for 24 months

• Treatment-Emergent Adverse Events

  Up to acalabrutinib treatment for 24 months

Study Arms (1)

previously untreated chronic lymphocytic leukemia.

EXPERIMENTAL

Previously untreated CLL patients with ≥1 of the IWCLL 2018 criteria for requiring treatment will be enrolled. Treatment with acalabrutinib may be continued until treatment for 24 months, or until an unacceptable drug-related toxicity occurs or until disease progression, whichever occurs first. Dose modification provisions are provided in the study protocol. Treatment with obinutuzumab or obinutuzumab/chlorambucil is up to 6 cycles per the obinutuzumab package insert.

Drug: Acalabrutinib; Drug: Obinutuzumab

Interventions

Acalabrutinib DRUG

100 mg capsules administered by mouth once daily (28-day cycles)

previously untreated chronic lymphocytic leukemia.

Obinutuzumab DRUG

100 mg administered intravenously on Day 1 and 900 mg administered intravenously on Day 2, 1000 mg administered intravenously on Day 8 and 15 of cycle 2 and 1000 mg on Day 1 of subsequent cycles for a total of 6 cycles (28-day cycles)

previously untreated chronic lymphocytic leukemia.

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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing
• Diagnosis of CD20+ CLL that meets published diagnostic criteria(Hallek 2018):
• Monoclonal B cells (either kappa or lambda light chain restricted) that are clonally co-expressing ≥ 1 B-cell marker (CD19, CD20, or CD23) and CD5.
• Prolymphocytes may comprise ≤ 55% of blood lymphocytes.
• Presence of ≥ 5 x 109 B lymphocytes/L (5000 μL) in the peripheral blood (at any point since diagnosis).
• Active disease meeting ≥ 1 of the following iwCLL 2018 criteria for requiring treatment:
• Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin \< 10 g/dL) and/or thrombocytopenia (platelets \< 100,000/μL).
• Massive (i.e., ≥ 6 cm below the left costal margin), progressive, or symptomatic splenomegaly.
• Massive nodes (i.e., ≥ 10 cm in the longest diameter), progressive, or symptomatic lymphadenopathy.
• Progressive lymphocytosis with an increase of \> 50% over a 2-month period or (lymphocyte doubling time) LDT of \< 6 months. LDT may be obtained by linear regression extrapolation of ALC obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In subjects with initial blood lymphocyte counts of \< 30 x 109/L (30,000/μL) may require a longer observation period to determine the LDT. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (e.g., infections) should be excluded.
• Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids.
• Constitutional symptoms documented in the subject's chart with supportive objective measures, as appropriate, defined as ≥ 1 of the following disease-related symptoms or signs:
• i Unintentional weight loss ≥ 10% within the previous 6 months before Screening.
• ii Significant fatigue (i.e., ECOG performance status 2; inability to work or perform usual activities).

You may not qualify if:

• Evidence of disease (such as severe or uncontrolled systemic diseases, including uncontrolled hypertension and renal transplant) that, in the investigator's opinion, make it undesirable for the patient to participate in the study or that would jeopardize compliance with the protocol.
• Any prior systemic treatment for CLL (note: Prior localized radiotherapy is allowed).
• Known CNS lymphoma or leukemia.
• Known prolymphocytic leukemia or history of, or currently suspected, Richter's syndrome.
• Uncontrolled AIHA or ITP defined as declining hemoglobin or platelet count secondary to autoimmune destruction within the screening period or requirement for high doses of steroids (\> 20 mg daily of prednisone daily or equivalent).
• Corticosteroid use \> 20 mg within 1 week before first dose of study drug, except as indicated for other medical conditions such as inhaled steroid for asthma, topical steroid use, or as premedication for administration of study drug or contrast. For example, subjects requiring steroids at daily doses \> 20 mg prednisone equivalent systemic exposure daily, or those who are administered steroids for leukemia control or WBC count lowering are excluded.
• Major surgery within 30 days before 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.
• History of prior malignancy that could affect compliance with the protocol or interpretation of results, except for the following:
• a. 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.
• b. 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.
• 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 at Screening. Note: Subjects with controlled, asymptomatic atrial fibrillation are allowed to enroll on study.
• History of or ongoing confirmed progressive multifocal leukoencephalopathy (PML).
• Received any investigational drug within 30 days or 5 half-lives (whichever is shorter) before first dose of study drug.
• Refractory nausea and vomiting, inability to swallow the formulated product, or malabsorption syndrome; chronic gastrointestinal disease, gastric restrictions, or bariatric surgery such as gastric bypass; partial or complete bowel obstruction, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of study treatment.
• Received a live virus vaccination within 28 days of first dose of study drug.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead
• AstraZeneca: collaborator

Study Sites (1)

Department of Haematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital

Nanjin, Jiangsu, 210029, China

RECRUITING

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

• Jianyong Li, PhD, MD

  The First Affiliated Hospital with Nanjing Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jianyong Li, PhD, MD

CONTACT

025-83718836; lijianyonglm@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2023
• First Posted: July 18, 2023
• Study Start: April 16, 2024
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: May 9, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)