Acalabrutinib in Patients With Relapsed/Refractory and Treatment naïve Deletion 17p CLL/SLL

Study Overview
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Brief Summary
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This study is to determine the response to acalabrutinib in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Detailed Description
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To investigate the safety and efficacy of acalabrutinib for patients with CLL/SLL that have relapsed/refractory disease or treatment naive deletion 17p.

Official Title
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A Phase II Study Using ACP-196 (Acalabrutinib) in Patients With Relapsed/Refractory and Treatment-naïve Deletion 17p CLL/SLL: Pharmacodynamic Assessment of BTK Inhibition and Antitumor Response.

Conditions
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Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

Intervention / Treatment
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* Drug: Acalabrutinib (Arm A)
* Drug: Acalabrutinib (Arm B)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women 18 years of age and older with histologically confirmed disease. Active disease as defined by at least one of the following (IWCLL consensus criteria): Weight loss ≥10% within the previous 6 months Extreme fatigue Fevers of greater than 100.5ºF for ≥2 weeks without evidence of infection Night sweats for more than one month without evidence of infection Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia Massive or progressive splenomegaly Massive nodes or clusters or progressive lymphadenopathy Progressive lymphocytosis with an increase of >50% over a 2 month period, or an anticipated doubling time of less than 6 months Compensated autoimmune hemolysis Relapsed/Refractory CLL or treatment naïve CLL patients with 17p deletion, TP53 mutation, or NOTCH1 mutation Agreement to use acceptable methods of contraception during the study and for 30 days after the last dose of study drug if sexually active and able to bear or beget children. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty and serial biopsies. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations). Exclusion Criteria: Radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or investigational products in the last 4 weeks. Richter's transformation. Autoimmune hemolytic anemia or thrombocytopenia requiring steroid therapy. Impaired hepatic function
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Subjects will be randomized to receive 1 of 2 dosing regimens: 1) acalabrutinib, dose A once daily; or 2) acalabrutinib, dose B twice daily. | Drug: Acalabrutinib (Arm A)<br>* A1a) acalabrutinib, dose A daily: biopsy (T) schedule W; A1b) acalabrutinib, dose A daily: biopsy (T) schedule V. A2a) acalabrutinib, dose B q 12 hours: biopsy (T) schedule Y; A2b) acalabrutinib, dose B q 12 hours; biopsy (T) schedule Z<br>* Other names: ACP-196;Drug: Acalabrutinib (Arm B)<br>* B1c) acalabrutinib, dose A daily: biopsy (U) schedule W; • B2c) acalabrutinib, dose B q12 hours: biopsy (U)) schedule Y.<br>* Other names: ACP-196;|
| Experimental: Arm B<br>Subjects will be randomized to receive 1 of 2 dosing regimens: 1) acalabrutinib, dose A once daily; or 2) acalabrutinib, dose B twice daily. | Drug: Acalabrutinib (Arm A)<br>* A1a) acalabrutinib, dose A daily: biopsy (T) schedule W; A1b) acalabrutinib, dose A daily: biopsy (T) schedule V. A2a) acalabrutinib, dose B q 12 hours: biopsy (T) schedule Y; A2b) acalabrutinib, dose B q 12 hours; biopsy (T) schedule Z<br>* Other names: ACP-196;Drug: Acalabrutinib (Arm B)<br>* B1c) acalabrutinib, dose A daily: biopsy (U) schedule W; • B2c) acalabrutinib, dose B q12 hours: biopsy (U)) schedule Y.<br>* Other names: ACP-196;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Based on Overall Response Rate | The best response to treatment was determined according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria incorporating 2012 and 2013 clarifications pertaining to subjects treated with kinase inhibitors. Overall response rate (ORR) was the proportion of subjects who achieved complete response (CR), CR with incomplete marrow recovery (CRi), or partial response (PR) while on treatment before the initiation of new anti-cancer therapy or stem cell transplant. | Cycle 1 (28 Days) to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsed/refractory CLL, Btk, Leukemia, Lymphocytic, Lymphoma, Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), ACP-196, Acalabrutinib, Treatment naive CLL, 17p deletion, TP53 mutation, NOTCH1 mutation