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

A Multicenter, Open-label, Phase 1 Pilot Study of ACP-196 in Combination With ACP-319 in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia

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)

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Lymphocytic Leukemia
• Intervention / Treatment: Drug: acalabrutinib; Drug: ACP-319

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Research Site
  • Tennessee
    • Hermitage, Tennessee, United States, 37076
      • Research Site
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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 Measures

Outcome Measure	Measure Description	Time Frame
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.	From 30 min before first dose to day-28 of cycle-6 of a 28 day cycle
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.	From 30 min before first dose to 30 min before day-28 of cycle-6 of 28 day cycles
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.	From 30 min before first dose till 30 before day-28 of cycle-6 of 28 day cycles
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.	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.
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).	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.
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).	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.

Collaborators and Investigators

• Sponsor: Acerta Pharma BV
• Investigators: Study Director: Acerta Clinical Trials, 1-888-292-9613 acertamc@dlss.com

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2014
• Primary Completion (Actual): July 20, 2020
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: May 30, 2014
• First Submitted That Met QC Criteria: June 4, 2014
• First Posted (Estimated): June 6, 2014

Study Record Updates

• Last Update Posted (Actual): August 13, 2025
• Last Update Submitted That Met QC Criteria: August 12, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Bruton tyrosine kinase inhibitor; Btk
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Acalabrutinib
• Other Study ID Numbers: ACE-CL-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No