Early Intervention With Acalabrutinib in Patients With High Risk CLL
- Registration Number
- NCT04660045
- Lead Sponsor
- Weill Medical College of Cornell University
- 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.
- Detailed Description
This is a multi-center, single arm, Phase II clinical trial to investigate the effectiveness of acalabrutinib treatment within 6 months of chronic lymphocytic leukemia (CLL) diagnosis for patients with CLL deemed at high risk for Richter's Transformation (RT).
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
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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.
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The time from diagnosis to consent should be ≤6 months.
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Subject must be ≥ 18 years of age.
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Subject must have diagnosis of CLL/SLL based upon 2018 iwCLL Guidelines.
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Rai stage 0-2 disease without indication for treatment as defined by the 2018 iwCLL guidelines
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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
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Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2.
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PT/PTT/INR within 1.5 x the ULN
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Adequate renal function defined by serum creatinine less than 2 x ULN
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Adequate hepatic function:
- ALT/AST less than 2x ULN
- Tbili less than 1.5 X ULN unless bilirubin elevation is due to Gilbert's syndrome (total bilirubin <3)
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Subject must have adequate bone marrow function.
- Absolute neutrophil count ≥1.0 x103/μL
- Hemoglobin ≥ 11.0 g/dL
- Platelets ≥ 100 x 103/μL
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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.
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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.
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Subject requires chronic immunosuppressive therapy for any reason or was treated with immunosuppressive therapy within 6 months of study entry.
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Subjects with a history of autoimmune hemolytic anemia or immune thrombocytopenia purpura.
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Subject has prolymphocytic leukemia.
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Active bleeding, or history of bleeding diathesis (e.g., hemophilia or von Willebrand disease)
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Subject requires warfarin or equivalent vitamin K antagonist
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Uncontrolled or active significant infection,
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History of or suspected or confirmed PML
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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.
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Patients with stroke or CNS hemorrhage within 6 months
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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.
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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.
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Has difficulty with or is unable to swallow oral medication or has significant gastrointestinal disease that would limit absorption of oral medication.
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Subject is known to be positive for human immunodeficiency virus (HIV)
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Active hepatitis C, as confirmed by being positive for Hep C RNA by PCR
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Active hepatitis B infection documented by a positive PCR for Hep B DNA. If hepatitis B serology is positive for hepatitis B core antibody, but Hep B DNA PCR is negative, patient is eligible to enroll.
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Subject requires strong CYP 3A4/5 inhibitors or inducers (Appendix B).
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Subject requires proton pump inhibitors. (Subjects that can transition to an H2 antagonist are allowed to enroll.)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Acalabrutinib Acalabrutinib Acalabrutinib 100 mg will be administered orally twice daily continuously in 28-day cycles until treatment is discontinued for any reason.
- Primary Outcome Measures
Name Time Method Percentage of subjects who do not develop Richter's Transformation (RT) within 5 years of study drug administration 5 years
- Secondary Outcome Measures
Name Time Method Event-free survival 5 years Measured from time of study drug administration to time of progression, transformation to a more aggressive histology, treatment discontinuation due to toxicity, or death from any cause.
Progression-free survival 5 years Measured from time of study drug administration to progression or death, measured in months.
Progression-free survival in patients with TP53 disruption 5 years For subjects with TP53 disruption present at baseline, measured from time of study drug administration to progression or death, measured in months.
Overall survival 5 years Measured from time of study drug administration to death from any cause, measured in months.
Percentage of subjects who do not develop Richter's Transformation within 2 years of study drug administration 2 years Median time to development of RT 5 years Measured from time of study drug administration
Safety of early interventional acalabrutinib in patients with chronic lymphocytic leukemia (CLL) at high risk for Richter's Transformation 5 years Percentage of subjects who experience 1 or more adverse events.
Trial Locations
- Locations (1)
Weill Cornell Medicine
🇺🇸New York, New York, United States