Study to Investigate the Use of Acalabrutinib in the Treatment of Patients With Chronic Lymphocytic Leukemia
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|ClinicalTrials.gov Identifier: NCT04178798|
Recruitment Status : Recruiting
First Posted : November 26, 2019
Last Update Posted : October 23, 2020
Study Phase III Randomized Study to Investigate the Use of Acalabrutinib in the Treatment of Patients with Early Stage CLL With High Risk of Early Disease Progression.
The study will consist of a screening phase, a treat¬ment/observation phase until progression, and a follow-up phase for progression in patients who discontinue treatment with Acalabrutinib without confirmed progression. Patients who progress will be followed for survival and initiation of subsequent antileukemic therapy. In the study, 130 patients from 20 centers in Spain with intermediate, high or very high risk will be randomized (1:1) to receive Acalabrutinib (n=65) or clinical observation (n=65). Acalabrutinib will be administered orally 100 mg twice daily on a continuous schedule.
Even though the majority of patients with CLL are currently diagnosed at early stages of the disease, there is a consensus that the standard of care in these patients is clinical observation (watch & wait) despite of the presence of risk factors for premature disease progression. Early treatment in patients with adverse prognostic parameters could prevent a disease evolving to a more advanced stage, and therefore more difficult to treat. So far, conventional chemotherapy did not show any benefit in terms of overall survival in patients with early stage CLL. (Dighiero 1998, Hoechstetter Leukemia 2017) Alongside this, treatment with chemotherapy may provoke two undesired effects: first, the occurrence of bone marrow toxicity that may hamper the subsequent administration of other treatments during the course of the disease; second, but not less relevant, genotoxic drug delivery may elicit a phenomenon of clonal selection leading to the appearance of CLL cells with genetic aberrations associated with refractoriness and aggressive outcome (i.e., TP53).
Against this background, it is of interest to investigate the role of new non-genotoxic drugs in the treatment of patients with CLL in early stages. Among different scores for selecting cases that are likely to progress rapidly, the German CLL Study Group (GCLLSG) risk score that includes 8 independent predictors for OS and PFS, differentiates patients with low-risk PFS vs. those with risk of early disease progression (median PFS 87 months vs. less than 27 months), allowing for a risk-adapted treatment approach in early stage CLL. (Pflug 2014, Langerbeins 2015).
Acalabrutinib, a second-generation, selective inhibitor of BTK, has shown substantial activity in patients with CLL. Acalabrutinib is a non-genotoxic drug active in cases with genetic lesions associated with chemorefratoriness and adverse outcome, including patients with alterations of TP53. Therefore, acalabrutinib represents a suitable compound for the treatment of patients with CLL in early stages with risk of early disease progression, including the high-risk CLL patient population with TP53 alterations.
|Condition or disease||Intervention/treatment||Phase|
|Chronic Lymphocytic Leukemia- Binet Staging System||Drug: Acalabrutinib 100 MG Oral Capsule||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||130 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||
|Masking:||None (Open Label)|
|Official Title:||Phase III Randomized Study to Investigate the Use of Acalabrutinib in the Treatment of Patients With Early Stage CLL With High Risk of Early Disease Progression|
|Actual Study Start Date :||December 9, 2019|
|Estimated Primary Completion Date :||October 1, 2024|
|Estimated Study Completion Date :||October 1, 2024|
Experimental: Arm A_Acalabrutinib
Patients assigned to arm A, will receive acalabrutinib as one capsule of 100 mg orally twice daily on a continuos schedule until disease progression, unacceptable toxicity or early withdrawal.
Drug: Acalabrutinib 100 MG Oral Capsule
Patients in Arm A will receive acalabrutinib as one capsule of 100 mg orally twice daily on a continuos Schedule.
No Intervention: Arm B_Standard of care
Patients assigned to arm B, will receive standard of care for the management of early Binet stage A patients "clinical observation (watch & wait)" until disease progression or early withdrawal.
- Event-Free Survival (EFS) [ Time Frame: From randomization to 60 months ]EFS is defined as the time between the date of randomization and time point of symptomatic disease progression with treatment indication according to the iwCLL-Guidelines, initiation of subsequent treatment for CLL or death by any cause, whichever occurs first.
- Progression-Free Survival (PFS) [ Time Frame: From randomization to 60 months ]Time between the date of randomization and progression of disease or death from any cause, whichever occurs first.
- Overall Survival (OS) [ Time Frame: From randomization to 60 months ]Time between the date of randomization and death from may cause.
- Time To Next Treatment (TTNT) [ Time Frame: From randomization to 60 months ]Time from randomization until the date of initiation of subsequent treatment for CLL or death from any cause.
- Objetive Response Rate (ORR) [ Time Frame: From randomization to 60 months ]Is defined as the proportion of patients who achieve a CR (Complete Remission), CRi (CR with incomplete bone marrow recovery), nPR (nodular Partial Remission) or PR (Partial Response) over the course of the study. Patients who achieve a PR with lymphocytosis will be included in the ORR. The rate of MRD-negative disease (MRD: Minimal Residual Disease) will also be calculated. The IWCLL guidelines (Hallek, 2018) will be used to measure response in CLL.
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): NCT04178798
|Contact: Olga García Calduch||0034 609 128 firstname.lastname@example.org|
|Contact: Carina Fernandez Mondino||0034 91 456 11 email@example.com|
|Principal Investigator:||Pau Abrisqueta Costa, MD||University Hospital of Vall d'Hebron|
|Principal Investigator:||Francesc Bosch Albareda, MD||University Hospital of Vall d'Hebron|
|Study Chair:||Carmen López Carrero||Fundación Pethema|