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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02328014
• Other study ID #: ACE-LY-001
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: December 20, 2014
• Est. completion date: April 1, 2026

Study information

• Verified date: April 2024
• Source: Acerta Pharma BV
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: April 1, 2026
• Est. primary completion date: June 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• B-All
• Multiple Myeloma
• Neoplasms
• Non-Hodgkins Lymphoma

Intervention

Drug:
• Acalabrutinib
Oral
• ACP-319
Oral

Locations

Country	Name	City	State
United States	Research Site	Austin	Texas
United States	Research Site	Bethesda	Maryland
United States	Research Site	Nashville	Tennessee
United States	Research Site	Orange	California
United States	Research Site	Portland	Oregon
United States	Research Site	Rochester	New York
United States	Research Site	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Acerta Pharma BV	AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	from the start of the treatment to the last evaluable disease assessment, an average of 1 year

External Links

•   redacted CSR synopsis
•   redacted SAP
•   redacted study protocol