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

NCT02157324 | Active Not Recruiting Phase 1

• 1 other identifier: ACE-CL-002
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 3

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)

Conditions

Chronic Lymphocytic Leukemia

Keywords

Bruton tyrosine kinase inhibitor; Btk

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• 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

• 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

• 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

• 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.

• 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.

Study Arms (2)

acalabrutinib

EXPERIMENTAL

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

Drug: acalabrutinib; Drug: ACP-319

ACP-319

EXPERIMENTAL

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

Drug: acalabrutinib; Drug: ACP-319

Interventions

acalabrutinib DRUG

Also known as: ACP-196

ACP-319; acalabrutinib

ACP-319 DRUG

ACP-319; acalabrutinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Acerta Pharma BV: lead

Study Sites (3)

Research Site

Columbus, Ohio, 43210, United States

Location

Research Site

Hermitage, Tennessee, 37076, United States

Location

Research Site

Fort Worth, Texas, 76104, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

acalabrutinib; N-(1-(7-fluoro-2-(pyridin-2-yl)quinolin-3-yl)ethyl)-9H-purin-6-amine

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Acerta Clinical Trials

  1-888-292-9613 acertamc@dlss.com

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2014
• First Posted: June 6, 2014
• Study Start: August 18, 2014
• Primary Completion: July 20, 2020
• Study Completion: April 1, 2026
• Last Updated: August 13, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• 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.
• 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.

Locations

US (3)