An Open-Label, Phase 1b Study of Acalabrutinib With and Without Dexamethasone in Subjects With Multiple Myeloma

NCT02211014 | Completed Phase 1 Results

• 1 other identifier: ACE-MY-001
• Study Type: interventional
• Target: 27
• Locations: 2 countries
• Sites: 3

Brief Summary

To characterize the safety profile of acalabrutinib with and without dexamethasone in subjects with relapsed or refractory Multiple Myeloma (MM)

Conditions

Multiple Myeloma (MM)

Keywords

Bruton tyrosine kinase inhibitor; Btk; Multiple Myeloma; MM; ACP-196; acalabrutinib; Calquence

Outcome Measures

Primary Outcomes (1)

• Safety Profile of Acalabrutinib With and Without Dexamethasone

  AEs and SAEs were coded by system organ class (SOC) and preferred term (PT) based on the Medical Dictionary for Regulatory Activities (MedDRA) reporting system. All AEs summarized were treatment-emergent. Summaries were also presented by the severity of the AE (per Common Toxicity Criteria for Adverse Events \[CTCAE\]) and by relationship to study drug as assessed by the investigator. Events of clinical interest (ECIs) selected for dedicated analysis were evaluated using Standardized MedDRA Queries, where available, by SOC, or by Sponsor-defined baskets of MedDRA Adverse Event Grouped Terms (AEGTs). The following ECIs were summarized: Cardiac events (including a subset of atrial fibrillation), cytopenias (anemia, leukopenia, neutropenia, and thrombocytopenia), hemorrhage (including a subset of major hemorrhage), hepatic events, hypertension, infection, interstitial lung disease/pneumonitis, second primary malignancies (second primary malignancies excluding skin), tumor lysis syndrome.

  From first dose of study drug up to Cycle 12 (48 weeks). Subjects who showed benefit from study drugs were allowed to continue until disease progression.

Secondary Outcomes (3)

• Pharmacokinetic (PK) Parameters Calculated for Acalabrutinib: AUC0-4, AUClast, AUCINF, Cmax, Tmax, λz, t1/2, CL/F, and Vz/F. PK Parameters Calculated for Dexamethasone: Tmax, Cmax, AUC0-4 and AUClast.

  On Days 1 and 22: pre-dose, and at 0.5, 0.75, 1, 2, 4, and 6 hours after the morning dose. On Days 8, 15, and 28: pre-dose and 1 hour after the morning dose.

• Bruton Tyrosine Kinase (BTK) Occupancy

  On Days 1 and 8: pre-dose and at 4 hours after the morning dose. On Days 28 and 56: morning pre-dose only.

• Response Assessed According to Guidelines Proposed by the International Myeloma Workshop Consensus Panel and European Group for Blood and Marrow Transplant

  From first dose of study drug up to Cycle 12 (48 weeks). Subjects who showed benefit from study drugs were allowed to continue until disease progression

Study Arms (2)

Cohort 1

EXPERIMENTAL

Acalabrutinib 100 mg twice daily (bid) continuously

Drug: acalabrutinib

Cohort 2

EXPERIMENTAL

Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly

Drug: acalabrutinib

Interventions

acalabrutinib DRUG

Also known as: ACP-196

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women ≥ 18 years of age.
• A confirmed diagnosis of MM, which has relapsed after, or been refractory to ≥ 1 prior therapy for MM, and is progressing at the time of study entry.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
• Agreement to use contraception during the study and for 30 days after the last dose of study drugs if sexually active and able to bear or beget children.

You may not qualify if:

• 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 acalabrutinib, or put the study outcomes at undue risk
• Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, gastric bypass, resection of the stomach or small bowel, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
• Breast feeding or pregnant

Sponsors & Collaborators

• Acerta Pharma BV: lead
• Acerta Pharma, LLC: collaborator

Study Sites (3)

Unknown Facility

Baltimore, Maryland, United States

Location

United Kingdom

Leicester, United Kingdom

Location

Guys and St Thomas' Hospital NHS Foundation Trust

London, United Kingdom

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

acalabrutinib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Acerta Clinical Trials
• Organization: Acerta Pharma B.V.

acertamc@dlss.com

1-888-292-9613

Study Officials

• Acerta Clinical Trials

  1-888-292-9613

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2014
• First Posted: August 7, 2014
• Study Start: February 1, 2015
• Primary Completion: April 26, 2019
• Study Completion: April 26, 2019
• Last Updated: July 31, 2020
• Results First Posted: May 13, 2020

Record last verified: 2020-07

Locations

GB (2); US (1)