ACP-196 (Acalabrutinib), a Novel Bruton Tyrosine Kinase (BTK) Inhibitor, for Treatment of Chronic… (NCT02029443) | Clinical Trial Compass
Active — Not RecruitingPhase 1/2
ACP-196 (Acalabrutinib), a Novel Bruton Tyrosine Kinase (BTK) Inhibitor, for Treatment of Chronic Lymphocytic Leukemia, Richter's Syndrome or Prolymphocytic Leukemia
United States306 participantsStarted 2014-01-30
Plain-language summary
This study is evaluating the safety and efficacy of a new BTK inhibitor, acalabrutinib, for the treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. Men and women ≥ 18 years of age with a confirmed diagnosis of CLL/SLL, which has relapsed after, or been refractory to, ≥ 2 previous treatments for CLL/SLL.
✓. Must have measurable CLL/SLL defined as ≥ 1 lymph node ≥ 2 cm as measured in the longest diameter.
✓. Active disease meeting ≥ 1 of the following International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 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 a lymphocyte doubling time (LDT) of \< 6 months. The LDT may be obtained by linear regression extrapolation of absolute lymphocyte counts (ALC) obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In participants with initial blood lymphocyte counts of \< 30 X 10\^9/L (30,000/μL), LDT should not be used as a single parameter to define indication for treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (eg, infections) should be excluded.
✓. Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy.
Exclusion criteria
✕. Prior malignancy, except for adequately treated basal cell, squamous cell skin cancer or in situ cervical cancer. Participants with other prior malignancies from which the participant has been disease free for ≥ 2 years may be included if approved by the medical monitor.
What they're measuring
1
Number of Participants With Dose Limiting Toxicities (DLTs) in Phase 1
Timeframe: From Day 1 to Day 28 after first dose of study drug
2
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Timeframe: Day 1 through the final data cutoff date (approximately 7 years 6 months)
3
Number of Participants With Treatment Emergent Events of Clinical Interest (ECI)
Timeframe: Day 1 through the final data cutoff date (approximately 7 years 6 months)
4
Number of Participants With Clinically Important Laboratory Abnormalities With Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or More
Timeframe: Day 1 through the final data cutoff date (approximately 7 years 6 months)
5
Number of Participants With Clinically Abnormal Vital Signs Reported as TEAEs
Timeframe: Day 1 through the final data cutoff date (approximately 7 years 6 months)
6
Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours (AUC0-6) of Acalabrutinib
Timeframe: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, and 6 hours postdose on Day 1 and Day 8
✕. A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the participant's safety, interfere with the absorption or metabolism of acalabrutinib, or put the study outcomes at undue risk.
✕. 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, or left ventricular ejection fraction (LVEF) ≤ 40%.
✕. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
✕. Any immunotherapy within 4 weeks of first dose of study drug.
✕. For participants with recent chemotherapy or experimental therapy the first dose of study drug must occur after 5 times the half-life of the agent(s).
✕. Relapsed after, or refractory to, prior BTK inhibitor therapy (Note: Does not apply to Ibrutinib R/R or Richter's Syndrome Group).
✕. Any history of Richter's transformation (Note: Does not apply to Richter's Syndrome Group).
Area Under the Plasma Concentration-time Curve From Time 0 to Last Measurable Concentration (AUC0-last) of Acalabrutinib
Timeframe: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8
8
Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of Acalabrutinib
Timeframe: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8
9
Maximum Observed Plasma Concentration (Cmax) of Acalabrutinib
Timeframe: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8
10
Time of Maximum Plasma Concentration (Tmax) of Acalabrutinib
Timeframe: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8
11
Terminal Elimination Half-life (t1/2) of Acalabrutinib
Timeframe: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8
12
Terminal Elimination Rate Constant (λz) of Acalabrutinib
Timeframe: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8
13
Apparent Oral Clearance (CL/F) of Acalabrutinib
Timeframe: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8
14
Apparent Volume of Distribution (Vz/F) of Acalabrutinib
Timeframe: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8