Early Intervention With Acalabrutinib in Patients With High Risk CLL

NCT04660045 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 20-11022876
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the effectiveness of acalabrutinib treatment in patients with chronic lymphocytic leukemia (CLL) deemed at high risk for Richter's Transformation (RT). This is a single arm study. Enrolled patients will initiate therapy with acalabrutinib and will dose continuously. While on study, subjects will be monitored monthly for the first 3 months, then every three months thereafter until disease progression, discontinuation due to toxicity, death, or study completion.

Conditions

Chronic Lymphocytic Leukemia; CLL/SLL

Keywords

CLL; untreated

Outcome Measures

Primary Outcomes (1)

• Percentage of subjects who do not develop Richter's Transformation (RT) within 5 years of study drug administration

  5 years

Secondary Outcomes (7)

• Event-free survival

  5 years

• Progression-free survival

  5 years

• Progression-free survival in patients with TP53 disruption

  5 years

• Overall survival

  5 years

• Percentage of subjects who do not develop Richter's Transformation within 2 years of study drug administration

  2 years

Study Arms (1)

Acalabrutinib

EXPERIMENTAL

Acalabrutinib 100 mg will be administered orally twice daily continuously in 28-day cycles until treatment is discontinued for any reason.

Drug: Acalabrutinib

Interventions

Acalabrutinib DRUG

Acalabrutinib, oral, 100 mg BID, continuous

Also known as: CALQUENCE, ACP-196

Acalabrutinib

Eligibility Criteria

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

You may qualify if:

• Subject must be able to voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study specific procedures.
• The time from diagnosis to consent should be ≤6 months.
• Subject must be ≥ 18 years of age.
• Subject must have diagnosis of CLL/SLL based upon 2018 iwCLL Guidelines.
• Rai stage 0-2 disease without indication for treatment as defined by the 2018 iwCLL guidelines
• Subject must have high risk CLL as defined by any one of the following:
• NOTCH1 mutated (classic frameshift mutation only)
• Unmutated V4-39 B cell receptor usage
• Pathogenic c-MYC mutations
• Complex karyotype, (by CpG/oligodeoxynucleotide stimulation)
• Deletion 17p, or presence of TP53 mutation
• Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2.
• PT/PTT/INR within 1.5 x the ULN
• Adequate renal function defined by serum creatinine less than 2 x ULN
• Adequate hepatic function:

You may not qualify if:

• Previous exposure to any systemic anti-cancer therapy as a treatment for CLL, including but not limited to chemotherapy, immunotherapy, radiotherapy, or investigational therapy. Note, patients treated with chemotherapy for a prior non-hematologic malignancy if more than 5 years earlier are eligible.
• Subject with a history of malignancy except for non-melanoma skin cancers. Subjects treated with curative intent via methods of local resection and or locally targeted anticancer treatment and are free of malignancy for at least 5 years from treatment end will be allowed to enroll.
• Subject requires chronic immunosuppressive therapy for any reason or was treated with immunosuppressive therapy within 6 months of study entry.
• Subjects with a history of autoimmune hemolytic anemia or immune thrombocytopenia purpura.
• Subject has prolymphocytic leukemia.
• Active bleeding, or history of bleeding diathesis (e.g., hemophilia or von Willebrand disease)
• Subject requires warfarin or equivalent vitamin K antagonist
• Uncontrolled or active significant infection,
• History of or suspected or confirmed PML
• Clinically significant cardiovascular disease such as uncontrolled or 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. Subjects with controlled, asymptomatic atrial fibrillation during screening can enroll on study.
• Patients with stroke or CNS hemorrhage within 6 months
• Pregnant or breastfeeding
• Women of childbearing potential (WCBP) who are sexually active with heterosexual partners must agree to use highly effective methods of contraception during treatment and for 2 days after the last dose of acalabrutinib.
• Major surgical procedure within 28 days of first dose of study drug. If a subject had surgery, they must have recovered adequately from any toxicity or complications before the first dose of study drug.
• Has difficulty with or is unable to swallow oral medication or has significant gastrointestinal disease that would limit absorption of oral medication.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• AstraZeneca: collaborator

Study Sites (1)

Weill Cornell Medicine

New York, New York, 10065, United States

Location

Related Links

• WCM Joint Clinical Trials Office

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

acalabrutinib

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

• John N Allan, M.D.

  Weill Medical College of Cornell University

  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

Study Record Dates

• First Submitted: December 2, 2020
• First Posted: December 9, 2020
• Study Start: May 1, 2022
• Primary Completion: January 1, 2026
• Study Completion: June 1, 2026
• Last Updated: April 5, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)