Clinical Trials /

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

NCT02157324

Description:

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)

Related Conditions:
  • Chronic Lymphocytic Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: ACE-CL-002
  • NCT ID: NCT02157324

Conditions

  • Chronic Lymphocytic Leukemia

Interventions

DrugSynonymsArms
acalabrutinibACP-196ACP-319
ACP-319ACP-319

Purpose

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)

Trial Arms

NameTypeDescriptionInterventions
acalabrutinibExperimentalStarts with acalabrutinib for 7 days, then combined with ACP-319 afterwards.
  • acalabrutinib
  • ACP-319
ACP-319ExperimentalStarts with ACP-319 for 7 days, then combined with acalabrutinib afterwards.
  • acalabrutinib
  • ACP-319

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Treatment-Emergent Adverse Events
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.
Safety Issue:
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.

Secondary Outcome Measures

Measure:Drug Exposure, Area Under the Plasma Concentration-time Curve
Time Frame:From 30 min before first dose to day-28 of cycle-6 of a 28 day cycle
Safety Issue:
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.
Measure:Drug Exposure, Maximum observed plasma concentration
Time Frame:From 30 min before first dose to 30 min before day-28 of cycle-6 of 28 day cycles
Safety Issue:
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.
Measure:Drug Exposure, Time of the maximum plasma concentration
Time Frame:From 30 min before first dose till 30 before day-28 of cycle-6 of 28 day cycles
Safety Issue:
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.
Measure:Overall Response rate
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.
Safety Issue:
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.
Measure:Duration of Response
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.
Safety Issue:
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).
Measure:Progression-Free Survival
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.
Safety Issue:
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).

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Acerta Pharma BV

Trial Keywords

  • Bruton tyrosine kinase inhibitor
  • Btk

Last Updated

July 2, 2021