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

Primary Purpose

Non-Hodgkins Lymphoma, Multiple Myeloma, B-All

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Acalabrutinib
ACP-319
Sponsored by
Acerta Pharma BV
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Hodgkins Lymphoma focused on measuring Bruton tyrosine kinase inhibitor, Btk, B-Cell Malignancies, Mantle Cell, Multiple Myeloma, CLL, SLL, DLBCL, Follicular, Waldenstrom, B-All

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dose Escalation and Expansion

Arm Description

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.

Outcomes

Primary Outcome Measures

Best Response and Overall Response Rate
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).

Secondary Outcome Measures

Full Information

First Posted
December 18, 2014
Last Updated
August 22, 2023
Sponsor
Acerta Pharma BV
Collaborators
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT02328014
Brief Title
Acalabrutinib (ACP-196) in Combination With ACP-319, for Treatment of B-Cell Malignancies
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 20, 2014 (Actual)
Primary Completion Date
June 1, 2020 (Actual)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Acerta Pharma BV
Collaborators
AstraZeneca

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Hodgkins Lymphoma, Multiple Myeloma, B-All
Keywords
Bruton tyrosine kinase inhibitor, Btk, B-Cell Malignancies, Mantle Cell, Multiple Myeloma, CLL, SLL, DLBCL, Follicular, Waldenstrom, B-All

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dose Escalation and Expansion
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Acalabrutinib
Other Intervention Name(s)
ACP-196
Intervention Description
Oral
Intervention Type
Drug
Intervention Name(s)
ACP-319
Intervention Description
Oral
Primary Outcome Measure Information:
Title
Best Response and Overall Response Rate
Description
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).
Time Frame
from the start of the treatment to the last evaluable disease assessment, an average of 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
AstraZeneca Clinical Study Infromation Center
Organizational Affiliation
1-877-240-9479 - information.center@astrazeneca.com
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Research Site
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Name
Research Site
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Research Site
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Research Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Research Site
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
Facility Name
Research Site
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home
Links:
URL
https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=ACE-LY-001&amp;attachmentIdentifier=24973127-5a2c-4c38-b322-8d5862f379df&amp;fileName=ACE-LY-001_SAP-v1_Redacted.pdf&amp;versionIdentifier=
Description
redacted SAP
URL
https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=ACE-LY-001&amp;attachmentIdentifier=903010aa-8039-41ba-9be1-5375d02fa590&amp;fileName=ACE-LY-001-CSR-Synopsis_Redacted.pdf&amp;versionIdentifier=
Description
redacted CSR synopsis
URL
https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=ACE-LY-001&amp;attachmentIdentifier=00a8f454-eb32-4da4-9d56-70d3a689b3a2&amp;fileName=ACE-LY-001_CSP_Redacted.pdf&amp;versionIdentifier=
Description
redacted study protocol

Learn more about this trial

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

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