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

Phase 2

Active, not recruiting

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

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

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Arm A	Acalabrutinib (Arm A)	Subjects will be randomized to receive 1 of 2 dosing regimens: 1) acalabrutinib, dose A once daily; or 2) acalabrutinib, dose B twice daily.
Arm B	Acalabrutinib (Arm B)	Subjects will be randomized to receive 1 of 2 dosing regimens: 1) acalabrutinib, dose A once daily; or 2) acalabrutinib, dose B twice daily.
Arm B	Acalabrutinib (Arm A)	Subjects will be randomized to receive 1 of 2 dosing regimens: 1) acalabrutinib, dose A once daily; or 2) acalabrutinib, dose B twice daily.
Arm A	Acalabrutinib (Arm B)	Subjects will be randomized to receive 1 of 2 dosing regimens: 1) acalabrutinib, dose A once daily; or 2) acalabrutinib, dose B twice daily.

Primary Outcome Measures

Name	Time	Method
Response Based on Overall Response Rate	Cycle 1 (28 Days) to 6 months	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.

Secondary Outcome Measures