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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02328014
Recruitment Status : Active, not recruiting
First Posted : December 31, 2014
Results First Posted : September 30, 2021
Last Update Posted : January 25, 2023
Information provided by (Responsible Party):
Acerta Pharma BV

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

Condition or disease Intervention/treatment Phase
Non-Hodgkins Lymphoma Multiple Myeloma B-All Drug: Acalabrutinib Drug: ACP-319 Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Proof-of-Concept Study of the Combination of ACP-196 and ACP-319 in Subjects With B-cell Malignancies
Actual Study Start Date : December 20, 2014
Actual Primary Completion Date : June 1, 2020
Estimated Study Completion Date : December 31, 2025

Resource links provided by the National Library of Medicine

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
Other Name: ACP-196

Drug: ACP-319

Primary Outcome Measures :
  1. 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).

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02328014

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United States, California
Research Site
Orange, California, United States, 92868
United States, Maryland
Research Site
Bethesda, Maryland, United States, 20892
United States, New York
Research Site
Rochester, New York, United States, 14642
United States, Oregon
Research Site
Portland, Oregon, United States, 97239
United States, Tennessee
Research Site
Nashville, Tennessee, United States, 37203
United States, Texas
Research Site
Austin, Texas, United States, 78705
United States, Washington
Research Site
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Acerta Pharma BV
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Study Director: AstraZeneca Clinical Study Infromation Center 1-877-240-9479 - information.center@astrazeneca.com
  Study Documents (Full-Text)

Documents provided by Acerta Pharma BV:
Study Protocol  [PDF] February 12, 2020
Statistical Analysis Plan  [PDF] February 3, 2020

Additional Information:
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Responsible Party: Acerta Pharma BV
ClinicalTrials.gov Identifier: NCT02328014    
Other Study ID Numbers: ACE-LY-001
First Posted: December 31, 2014    Key Record Dates
Results First Posted: September 30, 2021
Last Update Posted: January 25, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
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.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Keywords provided by Acerta Pharma BV:
Bruton tyrosine kinase inhibitor
B-Cell Malignancies
Mantle Cell
Multiple Myeloma
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Antineoplastic Agents