Back to resultsAcalabrutinib in Combination With ACP-319, for Treatment of Chronic Lymphocytic Leukemia
Primary Purpose
Chronic Lymphocytic Leukemia
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
acalabrutinib
ACP-319
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Lymphocytic Leukemia focused on measuring Bruton tyrosine kinase inhibitor, Btk
Eligibility Criteria
Inclusion Criteria:
- Men and women ≥ 18 years of age with a confirmed diagnosis of CLL, which has relapsed after, or been refractory to, ≥ 1 previous treatments for CLL; however, subjects with 17p deletion are eligible if they have relapsed after, or been refractory to, 1 prior treatment for CLL.
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
- Agreement to use contraception during the study and for 30 days after the last dose of study drugs if sexually active and able to bear or beget children.
Exclusion Criteria:
- Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for ≥ 2 years or which will not limit survival to < 2 years.
- A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of acalabrutinib and/or ACP-319, or put the study outcomes at undue risk.
- Significant cardiovascular disease.
- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
- Any immunotherapy within 4 weeks of first dose of study drug.
- For subjects with recent chemotherapy or experimental therapy the first dose of study drug must occur after 5 times the half-life of the agent(s).
- History of prior allogeneic bone marrow progenitor cell or solid organ transplantation.
- Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids for treatment of CLL or other conditions. Note: Subjects may be using topical or inhaled corticosteroids as therapy for comorbid conditions.
- Central nervous system (CNS) involvement by CLL.
- Grade ≥ 2 toxicity (other than alopecia).
- Known history of human immunodeficiency virus (HIV) or active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) or any uncontrolled active systemic infection.
- Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
- Absolute neutrophil count (ANC) < 0.75 x 109/L or platelet count < 50 x 109/L unless due to disease involvement in the bone marrow.
- Creatinine > 1.5 x institutional upper limit of normal (ULN); total bilirubin > 1.5 x ULN (unless due to Gilbert's disease); and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN unless disease related.
- Significant screening ECG abnormalities including left bundle branch block, 2nd degree AV block type II, 3rd degree block, Grade 2 or higher bradycardia, and QTc > 480 msec.
Sites / Locations
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
acalabrutinib
ACP-319
Arm Description
Starts with acalabrutinib for 7 days, then combined with ACP-319 afterwards.
Starts with ACP-319 for 7 days, then combined with acalabrutinib afterwards.
Outcomes
Primary Outcome Measures
Incidence of Treatment-Emergent Adverse Events
The frequency (number and percentage) of treatment-emergent AEs will be reported in each treatment group by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class and Preferred Term. Summaries will also be presented by the severity of the AE (per CTCAE, v4.03) and by relationship to study drug.
Secondary Outcome Measures
Drug Exposure, Area Under the Plasma Concentration-time Curve
PK sample schedule: Cycle 1 - Up to 30 minutes before dosing and 0.5, 1, 2, 4, 6, 12, 13, and 24 hours after the morning dose of Day 1 and 28. Also, 30 min before morning dose of cycle 1 - day 8,15 & 22, cycle 2 - day 15 & 28, and cycle 3 to 6 - day 28.
Drug Exposure, Maximum observed plasma concentration
PK sample schedule: Cycle 1 - Up to 30 minutes before dosing and 0.5, 1, 2, 4, 6, 12, 13, and 24 hours after the morning dose of Day 1 and 28. Also, 30 min before morning dose of cycle 1 - day 8,15 & 22, cycle 2 - day 15 & 28, and cycle 3 to 6 - day 28.
Drug Exposure, Time of the maximum plasma concentration
PK sample schedule: Cycle 1 - Up to 30 minutes before dosing and 0.5, 1, 2, 4, 6, 12, 13, and 24 hours after the morning dose of Day 1 and 28. Also, 30 min before morning dose of cycle 1 - day 8,15 & 22, cycle 2 - day 15 & 28, and cycle 3 to 6 - day 28.
Overall Response rate
A CT scan with contrast (unless contraindicated) of the neck, chest, abdomen, and pelvis and any other disease sites are required for the pretreatment tumor assessment.
Duration of Response
The duration of response is measured from the time measurement criteria are met for Complete Response or Partial Response (whichever is first recorded) until the first date that recurrent disease or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the study treatment started). Kaplan-Meier methodology will be used to estimate event-free curves and corresponding quantiles (including the median).
Progression-Free Survival
PFS is measured from the time of first study drug administration until the first date that recurrent disease or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the study treatment started). Kaplan-Meier methodology will be used to estimate the event-free curves and corresponding quantiles (including the median).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02157324
Brief Title
Acalabrutinib in Combination With ACP-319, for Treatment of Chronic Lymphocytic Leukemia
Official Title
A Multicenter, Open-label, Phase 1 Pilot Study of ACP-196 in Combination With ACP-319 in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 18, 2014 (Actual)
Primary Completion Date
July 20, 2020 (Actual)
Study Completion Date
May 31, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Acerta Pharma BV
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study is evaluating the safety and efficacy of the combined use of acalabrutinib and ACP-319, for the treatment of chronic lymphocytic leukemia (CLL)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia
Keywords
Bruton tyrosine kinase inhibitor, Btk
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
acalabrutinib
Arm Type
Experimental
Arm Description
Starts with acalabrutinib for 7 days, then combined with ACP-319 afterwards.
Arm Title
ACP-319
Arm Type
Experimental
Arm Description
Starts with ACP-319 for 7 days, then combined with acalabrutinib afterwards.
Intervention Type
Drug
Intervention Name(s)
acalabrutinib
Other Intervention Name(s)
ACP-196
Intervention Type
Drug
Intervention Name(s)
ACP-319
Primary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events
Description
The frequency (number and percentage) of treatment-emergent AEs will be reported in each treatment group by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class and Preferred Term. Summaries will also be presented by the severity of the AE (per CTCAE, v4.03) and by relationship to study drug.
Time Frame
From date of randomization until the day of documented progression or date of death from any cause, whichever came first, assessed up to 60 cycles of 28 days.
Secondary Outcome Measure Information:
Title
Drug Exposure, Area Under the Plasma Concentration-time Curve
Description
PK sample schedule: Cycle 1 - Up to 30 minutes before dosing and 0.5, 1, 2, 4, 6, 12, 13, and 24 hours after the morning dose of Day 1 and 28. Also, 30 min before morning dose of cycle 1 - day 8,15 & 22, cycle 2 - day 15 & 28, and cycle 3 to 6 - day 28.
Time Frame
From 30 min before first dose to day-28 of cycle-6 of a 28 day cycle
Title
Drug Exposure, Maximum observed plasma concentration
Description
PK sample schedule: Cycle 1 - Up to 30 minutes before dosing and 0.5, 1, 2, 4, 6, 12, 13, and 24 hours after the morning dose of Day 1 and 28. Also, 30 min before morning dose of cycle 1 - day 8,15 & 22, cycle 2 - day 15 & 28, and cycle 3 to 6 - day 28.
Time Frame
From 30 min before first dose to 30 min before day-28 of cycle-6 of 28 day cycles
Title
Drug Exposure, Time of the maximum plasma concentration
Description
PK sample schedule: Cycle 1 - Up to 30 minutes before dosing and 0.5, 1, 2, 4, 6, 12, 13, and 24 hours after the morning dose of Day 1 and 28. Also, 30 min before morning dose of cycle 1 - day 8,15 & 22, cycle 2 - day 15 & 28, and cycle 3 to 6 - day 28.
Time Frame
From 30 min before first dose till 30 before day-28 of cycle-6 of 28 day cycles
Title
Overall Response rate
Description
A CT scan with contrast (unless contraindicated) of the neck, chest, abdomen, and pelvis and any other disease sites are required for the pretreatment tumor assessment.
Time Frame
Pretreatment, then end of cycles 2, 4, 9, 12, 18 and then every 6 cycles to cycle 36. After that at cycle 48 and 60 of 28 day cycles.
Title
Duration of Response
Description
The duration of response is measured from the time measurement criteria are met for Complete Response or Partial Response (whichever is first recorded) until the first date that recurrent disease or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the study treatment started). Kaplan-Meier methodology will be used to estimate event-free curves and corresponding quantiles (including the median).
Time Frame
Pretreatment, then end of cycles 2, 4, 9, 12, 18 and then every 6 cycles to cycle 36. After that at cycle 48 and 60 of 28 day cycles.
Title
Progression-Free Survival
Description
PFS is measured from the time of first study drug administration until the first date that recurrent disease or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the study treatment started). Kaplan-Meier methodology will be used to estimate the event-free curves and corresponding quantiles (including the median).
Time Frame
Pretreatment, then end of cycles 2, 4, 9, 12, 18 and then every 6 cycles to cycle 36. After that at cycle 48 and 60 of 28 day cycles.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Men and women ≥ 18 years of age with a confirmed diagnosis of CLL, which has relapsed after, or been refractory to, ≥ 1 previous treatments for CLL; however, subjects with 17p deletion are eligible if they have relapsed after, or been refractory to, 1 prior treatment for CLL.
Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
Agreement to use contraception during the study and for 30 days after the last dose of study drugs if sexually active and able to bear or beget children.
Exclusion Criteria:
Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for ≥ 2 years or which will not limit survival to < 2 years.
A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of acalabrutinib and/or ACP-319, or put the study outcomes at undue risk.
Significant cardiovascular disease.
Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
Any immunotherapy within 4 weeks of first dose of study drug.
For subjects with recent chemotherapy or experimental therapy the first dose of study drug must occur after 5 times the half-life of the agent(s).
History of prior allogeneic bone marrow progenitor cell or solid organ transplantation.
Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids for treatment of CLL or other conditions. Note: Subjects may be using topical or inhaled corticosteroids as therapy for comorbid conditions.
Central nervous system (CNS) involvement by CLL.
Grade ≥ 2 toxicity (other than alopecia).
Known history of human immunodeficiency virus (HIV) or active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) or any uncontrolled active systemic infection.
Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
Absolute neutrophil count (ANC) < 0.75 x 109/L or platelet count < 50 x 109/L unless due to disease involvement in the bone marrow.
Creatinine > 1.5 x institutional upper limit of normal (ULN); total bilirubin > 1.5 x ULN (unless due to Gilbert's disease); and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN unless disease related.
Significant screening ECG abnormalities including left bundle branch block, 2nd degree AV block type II, 3rd degree block, Grade 2 or higher bradycardia, and QTc > 480 msec.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Acerta Clinical Trials
Organizational Affiliation
1-888-292-9613 acertamc@dlss.com
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Research Site
City
Hermitage
State/Province
Tennessee
ZIP/Postal Code
37076
Country
United States
Facility Name
Research Site
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.
All request will be evaluated as per the AZ disclosure commitment:
https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
IPD Sharing Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD Sharing Access Criteria
When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD Sharing URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home
Learn more about this trial
Acalabrutinib in Combination With ACP-319, for Treatment of Chronic Lymphocytic Leukemia
We'll reach out to this number within 24 hrs