Acalabrutinib in Combination With ACP-319, for Treatment of Chronic Lymphocytic Leukemia

Sponsor

Acerta Pharma BV (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02157324

Collaborator

(none)

Enrollment

Locations

Arms

136.4

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

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)

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia	Drug: acalabrutinib Drug: ACP-319	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Aug 18, 2014

Actual Primary Completion Date :

Jul 20, 2020

Anticipated Study Completion Date :

Dec 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: acalabrutinib Starts with acalabrutinib for 7 days, then combined with ACP-319 afterwards.	Drug: acalabrutinib Other Names: ACP-196 Drug: ACP-319
Experimental: ACP-319 Starts with ACP-319 for 7 days, then combined with acalabrutinib afterwards.	Drug: acalabrutinib Other Names: ACP-196 Drug: ACP-319

Arm

Intervention/Treatment

Experimental: acalabrutinib

Starts with acalabrutinib for 7 days, then combined with ACP-319 afterwards.

Drug: acalabrutinib

Other Names:

ACP-196

Drug: ACP-319

Experimental: ACP-319

Starts with ACP-319 for 7 days, then combined with acalabrutinib afterwards.

Drug: acalabrutinib

Other Names:

ACP-196

Drug: ACP-319

Outcome Measures

Primary Outcome Measures

Incidence of Treatment-Emergent Adverse Events [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.]
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 [From 30 min before first dose to day-28 of cycle-6 of a 28 day cycle]
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 [From 30 min before first dose to 30 min before day-28 of cycle-6 of 28 day cycles]
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 [From 30 min before first dose till 30 before day-28 of cycle-6 of 28 day cycles]
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 [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.]
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 [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.]
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 [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.]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.