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

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: NCT02211014
Recruitment Status : Completed
First Posted : August 7, 2014
Results First Posted : May 13, 2020
Last Update Posted : July 31, 2020
Acerta Pharma, LLC
Information provided by (Responsible Party):
Acerta Pharma BV

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

Condition or disease Intervention/treatment Phase
Multiple Myeloma (MM) Drug: acalabrutinib Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Phase 1b Study of ACP-196 With and Without Dexamethasone in Subjects With Multiple Myeloma
Actual Study Start Date : February 2015
Actual Primary Completion Date : April 26, 2019
Actual Study Completion Date : April 26, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Cohort 1
Acalabrutinib 100 mg twice daily (bid) continuously
Drug: acalabrutinib
Other Name: ACP-196

Experimental: Cohort 2
Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly
Drug: acalabrutinib
Other Name: ACP-196

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

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): NCT02211014

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United States, Maryland
Baltimore, Maryland, United States
United Kingdom
United Kingdom
Leicester, United Kingdom
Guys and St Thomas' Hospital NHS Foundation Trust
London, United Kingdom
Sponsors and Collaborators
Acerta Pharma BV
Acerta Pharma, LLC
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Study Director: Acerta Clinical Trials 1-888-292-9613
  Study Documents (Full-Text)

Documents provided by Acerta Pharma BV:
Study Protocol  [PDF] January 13, 2016
Statistical Analysis Plan  [PDF] September 20, 2018

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Responsible Party: Acerta Pharma BV
ClinicalTrials.gov Identifier: NCT02211014    
Other Study ID Numbers: ACE-MY-001
First Posted: August 7, 2014    Key Record Dates
Results First Posted: May 13, 2020
Last Update Posted: July 31, 2020
Last Verified: July 2020
Keywords provided by Acerta Pharma BV:
Bruton tyrosine kinase inhibitor
Multiple Myeloma
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Antineoplastic Agents