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

July 15, 2020 updated by: Acerta Pharma BV

An Open-Label, Phase 1b Study of ACP-196 With and Without Dexamethasone in Subjects With Multiple Myeloma

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
27

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Leicester, United Kingdom
        • United Kingdom
      • London, United Kingdom
        • Guys and St Thomas' Hospital NHS Foundation Trust
  • United States
    • Maryland
      • Baltimore, Maryland, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.

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 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Cohort 1
Acalabrutinib 100 mg twice daily (bid) continuously
Drug: acalabrutinib
Other Names:
  • ACP-196
EXPERIMENTAL: Cohort 2
Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly
Drug: acalabrutinib
Other Names:
  • ACP-196

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Safety Profile of Acalabrutinib With and Without Dexamethasone
Time Frame: 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.
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Time Frame: 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.
The plasma PK of study drug was characterized using noncompartmental analysis. PK parameters were calculated whenever possible, from plasma concentrations of acalabrutinib. Missing dates or times could have been imputed for PK and pharmacodynamic (PD) samples if the missing values could be established with an acceptable level of accuracy based on other information obtained during the visit in question. If PK and PD sampling for a 33 Final Clinical Study Report Drug Substance Acalabrutinib Study Code ACE-MY-001 Edition Number 2 Date 31 October 2018 given subject was not performed according to protocol, the subject could have been excluded from the PK and PD analyses. The PK parameters were tabulated and summarized using descriptive statistics. For each PD variable, the concentration at each assessment was described. The change from baseline to each assessment was summarized. As appropriate the on treatment values were compared with the pretreatment baseline values using paired t-tests.
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
Time Frame: On Days 1 and 8: pre-dose and at 4 hours after the morning dose. On Days 28 and 56: morning pre-dose only.
The percent occupied BTK was calculated in each subject's peripheral blood mononuclear cells (PBMC) sample for each assessment timepoint using an ELISA-based method. Samples from 17 subjects met the criteria for data inclusion, having a dynamic range (signal to noise) of ≥5 for the Day 1 pre-dose timepoint. Acalabrutinib administered at 100 mg bid resulted in a median steady-state (Day 8) BTK target occupancy level of 95% and 98% for Cohort 1 and Cohort 2, respectively. The Days 28 and 56 assessments, both taken at pre-dose, were >97% occupancy for each cohort. Intersubject variability was low, with 6 of 7 (86%) subjects in Cohort 1 and 4 of 5 (80%) subjects in Cohort 2 having >90% BTK occupancy at steady-state trough (12h post-dose). The single subject in Cohort 2 with <90% occupancy at Day 8 pre-dose did not take their Day 7 doses.
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
Time Frame: 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
Per EBMT: CR, negative immunofixation of serum and urine, disappearance of plasmacytomas and < 5% plasma cells; Stringent complete response (SCR), CR + normal flow cytometry and absence of clonal plasma cells; Very good partial response (VGPR), Serum and urine M-protein detectable on immunofixation but not on electrophoresis or > 90% reduction is serum and urine M protein; Partial response (PR), > 50% reduction in serum M-protein and > 90% reduction in 24 hour urine M-protein, > 50% reduction in baseline soft tissue plasmacytoma; Minimal response (MR), 25-49% reduction of serum M-protein and 50-59% reduction in 24 hour urine M-protein, 25-49% reduction in plasmacytomas and no increase in lytic bone lesions; Stable disease (SD), not meeting criteria for CR, VGPR, MR, PR or progressive disease (PD); PD, increase of 25% or more from nadir in serum M-protein, urine M-protein, new or increased bone lesions or plasmacytomas, or hypercalcemia solely attributed to multiple myeloma.
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Acerta Pharma BV

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Acerta Pharma, LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2015

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 26, 2019

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 26, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 5, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 5, 2014

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 7, 2014

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 31, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 15, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ACE-MY-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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