Acalabrutinib (ACP-196) in Combination With ACP-319, for Treatment of B-Cell Malignancies

November 25, 2025 updated by: Acerta Pharma BV

A Phase 1/2 Proof-of-Concept Study of the Combination of ACP-196 and ACP-319 in Subjects With B-cell Malignancies

This study is evaluating the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy acalabrutinib and ACP 319 in B-cell malignancies.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Part 1, Dose Escalation, is comprised of 3 dosing cohorts of 6 subjects each. Acalabrutinib dosing is fixed in all cohorts at 100 mg PO twice daily (BID). In addition to acalabrutinib, subjects in Cohort 1 will receive ACP-319, 25 mg BID; Cohort 2 will receive ACP-319, 50 mg BID: and Cohort 3 will receive ACP-319 100 mg BID. The maximum tolerated dose (MTD) of the study treatment combination will be determined by assessing dose-related toxicities (DLTs) for each cohort at the end of Cycle 1 prior to dose escalation. If there are greater than or equal to 2 DLTs in a cohort, dose escalation will not occur and the MTD will be the highest daily dose for which less than 33% of the subjects in that cohort experienced DLTs in Cycle 1.

Part 2, Dose Expansion, includes 12 subjects per histology, dosing at the MTD for the combination of acalabrutinib and ACP-319 established in Part 1. Subjects will continue dosing until disease progression or unacceptable drug-related toxicity.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Orange, California, United States, 92868
        • Research Site
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • Research Site
    • New York
      • Rochester, New York, United States, 14642
        • Research Site
    • Oregon
      • Portland, Oregon, United States, 97239
        • Research Site
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Research Site
    • Texas
      • Austin, Texas, United States, 78705
        • Research Site
    • Washington
      • Seattle, Washington, United States, 98109
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Main Inclusion Criteria:

  • Diagnosis of a b-cell malignancy as documented by medical records and with histology based on criteria established by the World Health Organization (WHO).
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
  • Agreement to use contraception during the study and for 90 days after the last dose of study drugs if sexually active and able to bear or beget children.

Exclusion Criteria

  • 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 study drugs, or put the study outcomes at undue risk.
  • Central nervous system (CNS) involvement by lymphoma/leukemia
  • Any therapeutic antibody within 4 weeks of first dose of study drugs.
  • The time from the last dose of the most recent chemotherapy or experimental therapy to the first dose of study drugs is < 5 times the half-life of the previously administered agent(s).
  • ANC < 0.5 x 10^9/L or platelet count < 50 x 10^9/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) > 3.0 x ULN.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose Escalation and Expansion

The acalabrutinib dose will be fixed and the ACP-319 dose will be escalated in each of three cohorts, and each cohort will take both study drugs by mouth, twice per day (BID) at approximately 12 hour intervals.

Expansion groups of up to 12 subjects for Germinal center B-cell (GCB) DLBCL and Non-GCB DLBCL to take a fixed dose of acalabrutinib and ACP-319. Each disease group will take both study drugs by mouth, twice per day (BID) at approximately 12 hour intervals.
Drug: Acalabrutinib
Oral
Other Names:
  • ACP-196
Drug: ACP-319
Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Best Response and Overall Response Rate
Time Frame: from the start of the treatment to the last evaluable disease assessment, an average of 1 year
Best response and overall response rate per the criteria investigator uses for each disease histology. Standardized response and progression criteria is based on established criteria for B-cell malignancies, including WM (Cheson 2014; Owen 2013; Hallek 2008; Bladé 1998; and Durie 2006).
from the start of the treatment to the last evaluable disease assessment, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Acerta Pharma BV

Collaborators

AstraZeneca

Investigators

  • Study Director: AstraZeneca Clinical Study Infromation Center, 1-877-240-9479 - information.center@astrazeneca.com

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 20, 2014

Primary Completion (Actual)

June 1, 2020

Study Completion (Actual)

October 30, 2025

Study Registration Dates

First Submitted

December 18, 2014

First Submitted That Met QC Criteria

December 26, 2014

First Posted (Estimated)

December 31, 2014

Study Record Updates

Last Update Posted (Estimated)

December 9, 2025

Last Update Submitted That Met QC Criteria

November 25, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACE-LY-001

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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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