Acalabrutinib Safety Study in Untreated and Relapsed or Refractory Chronic Lymphocytic Leukemia Patients (ASSURE)
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|ClinicalTrials.gov Identifier: NCT04008706|
Recruitment Status : Active, not recruiting
First Posted : July 5, 2019
Last Update Posted : October 3, 2022
|Condition or disease||Intervention/treatment||Phase|
|Chronic Lymphocytic Leukemia||Drug: Acalabrutinib||Phase 3|
This is a Global, Phase 3b, multicenter, open-label, single-arm study to evaluate the safety and efficacy of acalabrutinib 100 mg bid in approximately 540 participants with CLL. Participants will be enrolled into 3 cohorts: treatment-naive (TN): participants who have had no prior treatment for CLL and who have either a score > 6 on the cumulative illness rating scale and/or have a creatinine clearance of 30 to 69 mL/min using the Cockcroft-Gault equation (minimum of 300 participants), relapsed/refractory (R/R): participants who have received prior treatment for CLL and who have either relapsed or refractory CLL (approximately 200 participants), and prior bruton tyrosine kinase inhibitor (BTKi) therapy: participants who have received prior ibrutinib for CLL and who discontinued the medication for any reason prior to disease progression (up to 40 participants). Overall response and progression assessments will be conducted by the investigator in accordance with the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 criteria. Overall response assessments will be based on evaluation of physical examinations, recording of symptoms, radiologic evaluations, and hematologic evaluations.
Treatment period consists of 48 cycles [each cycle is 28 days). Study treatment (acalabrutinib 100 mg bid) will be administered until disease progression, toxicity requiring discontinuation, completion of 48 cycles of study treatment, withdrawal of consent, loss to follow-up, death, or study termination by the sponsor, whichever comes first.
48 Cycles: From Cycle 1 to Cycle 6, in-clinic visits will occur every cycle and during each visit, in-clinic assessments will be carried out. From Cycle 6 to Cycle 12, in-clinic visits will occur every 3 cycles and during each visit, in-clinic assessments will be carried out. From Cycle 13 to Cycle 48, in-clinic visits will occur every 3 cycles and in-clinic assessments will be carried out every 6 cycles.
Safety follow up visits will occur approximately 30 days from the last dose of study treatment.
If a participant continues to derive benefit from treatment at the end of 48 cycles prior to the final DCO, they will continue to be provided with study treatment. Post-DCO, 2 options will be considered: patients may be transitioned to another study or may shift to a commercial supply of acalabrutinib/off-study acalabrutinib as permitted by local regulation. Subjects who switch to off-study acalabrutinib will be considered as having completed the study and therefore will not have any additional study assessments, including the disease Follow-up period.
The duration of the study will be approximately 72 months from the first participant enrolled. This duration includes an estimated 24-month recruitment time and an assumed 48 cycles of study treatment (28 days per cycle); additional study time will be accrued during the Follow-up period for those participants remaining on study treatment after completion of 48 cycles prior to the final DCO (the amount of time will vary by participant).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||553 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||This is a single arm study in which participants will be enrolled into 3 cohorts. In the treatment-naive (TN) cohort, a minimum of 300 participants with treatment-naïve chronic lymphocytic leukemia will be enrolled. In the relapsed/refractory (R/R) cohort, approximately 200 participants with relapsed/refractory chronic lymphocytic leukemia will be enrolled. In the prior Bruton tyrosine kinase inhibitor (BTKi) therapy cohort, up to 70 to 100 participants with Prior BTKi therapy will be enrolled.|
|Masking:||None (Open Label)|
|Official Title:||A Phase 3b, Multicenter, Open-Label, Single-Arm Study of Acalabrutinib (ACP-196) in Subjects With Chronic Lymphocytic Leukemia.|
|Actual Study Start Date :||September 17, 2019|
|Estimated Primary Completion Date :||September 1, 2025|
|Estimated Study Completion Date :||September 1, 2025|
Participants will be enrolled into 3 cohorts. In the treatment-naive (TN) cohort, a minimum of 300 participants with treatment-naïve chronic lymphocytic leukemia will be enrolled. In the relapsed/refractory (R/R) cohort, approximately 200 participants with relapsed/refractory chronic lymphocytic leukemia will be enrolled. In the prior Bruton tyrosine kinase inhibitor (BTKi) therapy cohort, approximately 40 participants with Prior BTKi therapy will be enrolled.
Acalabrutinib will be administered as one 100 mg capsule taken orally, twice daily with 8 ounces (approximately 240 mL) of water.
Other Name: ACP-196
- Number of participants with adverse events [ Time Frame: From screening to safety follow-up period (approximately 30 days from last dose) ]To evaluate the safety and tolerability of acalabrutinib monotherapy in participants with TN or R/R CLL.
- Overall response (OR) [ Time Frame: 1 year after initial dose of study drug ]To evaluate the investigator-assessed OR in participants receiving acalabrutinib monotherapy.
- Duration of response (DOR) [ Time Frame: The time from the first objective response to the time of documented disease progression or death due to any cause, whichever occurs first within the time period to complete up to 48 cycles of treatment (each cycle is 28 days) ]To evaluate the investigator-assessed DOR in participants receiving acalabrutinib monotherapy.
- Progression-free survival (PFS) [ Time Frame: The interval from the start of study treatment to completion of 48 cycles (each cycle is 28 days) or the earlier of the first documentation of disease progression or death from any cause ]To evaluate the investigator-assessed PFS in participants receiving acalabrutinib monotherapy.
- Plasma concentrations of acalabrutinib and ACP 5862 [ Time Frame: At Day 1 of Cycle 3 and Day 1 of Cycle 15 ]To characterize the pharmacokinetics of acalabrutinib and its metabolite (ACP-5862).
- Overall survival (OS) [ Time Frame: Up to 48 Cycles (each cycle is 28 days) or as long as participant remains on the study (maximum up to 1 year) ]To evaluate OS in participants receiving acalabrutinib monotherapy.
- Time to next treatment [ Time Frame: From the start of study treatment to safety follow-up period (approximately 30 days from last dose) ]To evaluate the time to next treatment.
- European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) [ Time Frame: Up to 48 cycles (each cycle is 28 days) ]To evaluate participant-reported symptoms and health-related quality of life following treatment with acalabrutinib monotherapy. EORTC QLQ-C30 scale scores range from 0 to 100. A higher score represents a higher ("better") level of functioning, or a higher ("worse") level of symptoms.
- Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) [ Time Frame: Up to 48 cycles (each cycle is 28 days) ]To evaluate participant-reported symptoms following treatment with acalabrutinib monotherapy using PRO-CTCAE. Patient-reported outcomes (PROs), an umbrella term referring to all outcomes and symptoms, are directly reported by the participant. Around 81 symptoms of the CTCAE v4 have been identified to be amenable to participant reporting. These symptoms have been converted to participant terms (e.g., CTCAE term "myalgia" converted to "aching muscles"). For several symptoms, like fatigue and pain, additional questions are asked about symptom frequency (never to almost constantly), severity (none to very severe, and interference with usual activities (not at all to very much). For this study, the following items are considered relevant and will be assessed: headache, diarrhea, fatigue, nausea, vomiting, abdominal pain, rash, muscle pain, nose bleed, heart palpitations, bruising, joint pain, and constipation.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04008706
|Study Director:||Adel Habib, MD||AstraZeneca|
|Principal Investigator:||Dr. Carsten Niemann, MD||Rigshospitalet, Denmark|