Chronic Lymphocytic Leukemia
Conditions
Keywords
Bruton tyrosine kinase inhibitor, Btk
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)
Interventions
DRUGacalabrutinib
DRUGACP-319
Sponsors
Acerta Pharma BV
Study design
Allocation
NON_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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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). |
| 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. |
Countries
United States
Outcome results
None listed