Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Conditions
Keywords
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
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.
Interventions
DRUGAcalabrutinib (Arm A)
* 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
DRUGAcalabrutinib (Arm B)
B1c) acalabrutinib, dose A daily: biopsy (U) schedule W; • B2c) acalabrutinib, dose B q12 hours: biopsy (U)) schedule Y.
Sponsors
Acerta Pharma BV
National Institutes of Health (NIH)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Contacts
STUDY_DIRECTORAstraZeneca Clinical Study Information Center
1-877-240-9479 - information.center@astrazeneca.com
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Acalabrutinib 100 mg BID Relapse/Refractory relapsed/refractory subjects treated with acalabrutinib 100 mg twice a day | 18 |
| Acalabrutinib 200 mg QD Relapse/Refractory Relapse/Refractory subjects treated with acalabrutinib 200 mg once a day | 14 |
| Acalabrutinib 100 mg BID Treatment Naive Treatment naive subjects treated with acalabrutinib 100 mg twice a day | 6 |
| Acalabrutinib 200 mg QD Treatment Naive Treatment naive subjects treated with acalabrutinib 200 mg once a day | 10 |
| Total | 48 |
Baseline characteristics
| Characteristic | Total | Acalabrutinib 200 mg QD Treatment Naive | Acalabrutinib 100 mg BID Treatment Naive | Acalabrutinib 100 mg BID Relapse/Refractory | Acalabrutinib 200 mg QD Relapse/Refractory |
|---|---|---|---|---|---|
| Age, Continuous | 63.4 Years STANDARD_DEVIATION 8.9 | 62.1 Years STANDARD_DEVIATION 8.7 | 68.3 Years STANDARD_DEVIATION 10.9 | 63.3 Years STANDARD_DEVIATION 9.3 | 62.3 Years STANDARD_DEVIATION 7.7 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 5 Participants | 1 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 47 Participants | 9 Participants | 6 Participants | 18 Participants | 14 Participants |
| Race/Ethnicity, Customized Not Reported | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 39 Participants | 7 Participants | 4 Participants | 16 Participants | 12 Participants |
| Region of Enrollment United States | 48 Participants | 10 Participants | 6 Participants | 18 Participants | 14 Participants |
| Sex: Female, Male Female | 15 Participants | 4 Participants | 2 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Male | 33 Participants | 6 Participants | 4 Participants | 12 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 1 / 14 | 0 / 6 | 0 / 10 |
| other Total, other adverse events | 18 / 18 | 14 / 14 | 6 / 6 | 10 / 10 |
| serious Total, serious adverse events | 11 / 18 | 8 / 14 | 3 / 6 | 5 / 10 |
Outcome results
Primary
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.
Time frame: Cycle 1 (28 Days) to 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acalabrutinib 100 mg BID Relapse/Refractory | Response Based on Overall Response Rate | 17 Participants |
| Acalabrutinib 200 mg QD Relapse/Refractory | Response Based on Overall Response Rate | 11 Participants |
| Total Relapse/Refractory Subjects | Response Based on Overall Response Rate | 28 Participants |
| Acalabrutinib 100 mg BID Treatment Naive | Response Based on Overall Response Rate | 6 Participants |
| Acalabrutinib 200 mg QD Treatment Naive | Response Based on Overall Response Rate | 8 Participants |
| Total Treatment Naive Subjects | Response Based on Overall Response Rate | 14 Participants |