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
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|Condition or disease||Intervention/treatment||Phase|
|Non-Hodgkins Lymphoma Multiple Myeloma B-All||Drug: Acalabrutinib Drug: ACP-319||Phase 1 Phase 2|
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 (Clinical Trial)|
|Actual Enrollment :||40 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|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|
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.
Other Name: ACP-196
- 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).
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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.
- 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.
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
|United States, California|
|Orange, California, United States, 92868|
|United States, Maryland|
|Bethesda, Maryland, United States, 20892|
|United States, New York|
|Rochester, New York, United States, 14642|
|United States, Oregon|
|Portland, Oregon, United States, 97239|
|United States, Tennessee|
|Nashville, Tennessee, United States, 37203|
|United States, Texas|
|Austin, Texas, United States, 78705|
|United States, Washington|
|Seattle, Washington, United States, 98109|
|Study Director:||AstraZeneca Clinical Study Infromation Center||1-877-240-9479 - email@example.com|
Documents provided by Acerta Pharma BV:
|Responsible Party:||Acerta Pharma BV|
|Other Study ID Numbers:||
|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|
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.
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.|
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