Description:
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.
Title
- Brief Title: Early Intervention With Acalabrutinib in Patients With High Risk CLL
- Official Title: A Phase II Trial of Early Intervention With Acalabrutinib in Patients With CLL at High Risk for Richter's Transformation
Clinical Trial IDs
- ORG STUDY ID:
20-11022876
- NCT ID:
NCT04660045
Conditions
- Chronic Lymphocytic Leukemia
- CLL/SLL
Interventions
Drug | Synonyms | Arms |
---|
Acalabrutinib | CALQUENCE, ACP-196 | Acalabrutinib |
Purpose
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).
Trial Arms
Name | Type | Description | Interventions |
---|
Acalabrutinib | Experimental | Acalabrutinib 100 mg will be administered orally twice daily continuously in 28-day cycles until treatment is discontinued for any reason. | |
Eligibility Criteria
Inclusion Criteria:
- 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:
- 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)
- Subject must have adequate bone marrow function.
- Absolute neutrophil count ≥1.0 x103/μL
- Hemoglobin ≥ 11.0 g/dL
- Platelets ≥ 100 x 103/μL
Exclusion Criteria:
- 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.
- Subject is known to be positive for human immunodeficiency virus (HIV)
- Active hepatitis C, as confirmed by being positive for Hep C RNA by PCR
- 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.
- Subject requires strong CYP 3A4/5 inhibitors or inducers (Appendix B).
- Subject requires proton pump inhibitors. (Subjects that can transition to an H2
antagonist are allowed to enroll.)
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Percentage of subjects who do not develop Richter's Transformation (RT) within 5 years of study drug administration |
Time Frame: | 5 years |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Event-free survival |
Time Frame: | 5 years |
Safety Issue: | |
Description: | 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. |
Measure: | Progression-free survival |
Time Frame: | 5 years |
Safety Issue: | |
Description: | Measured from time of study drug administration to progression or death, measured in months. |
Measure: | Progression-free survival in patients with TP53 disruption |
Time Frame: | 5 years |
Safety Issue: | |
Description: | For subjects with TP53 disruption present at baseline, measured from time of study drug administration to progression or death, measured in months. |
Measure: | Overall survival |
Time Frame: | 5 years |
Safety Issue: | |
Description: | Measured from time of study drug administration to death from any cause, measured in months. |
Measure: | Percentage of subjects who do not develop Richter's Transformation within 2 years of study drug administration |
Time Frame: | 2 years |
Safety Issue: | |
Description: | |
Measure: | Median time to development of RT |
Time Frame: | 5 years |
Safety Issue: | |
Description: | Measured from time of study drug administration |
Measure: | Safety of early interventional acalabrutinib in patients with chronic lymphocytic leukemia (CLL) at high risk for Richter's Transformation |
Time Frame: | 5 years |
Safety Issue: | |
Description: | Percentage of subjects who experience 1 or more adverse events. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Not yet recruiting |
Lead Sponsor: | Weill Medical College of Cornell University |
Trial Keywords
Last Updated
June 25, 2021