Multiple Myeloma (MM)Phase 1NCT02211014
An Open-Label, Phase 1b Study of Acalabrutinib With and Without Dexamethasone in Subjects With Multiple Myeloma
A Phase 1 study testing acalabrutinib in people with Multiple Myeloma (MM), run by Acerta Pharma BV at 3 sites in 2 countries.
Trial summary
To characterize the safety profile of acalabrutinib with and without dexamethasone in subjects with relapsed or refractory Multiple Myeloma (MM) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma (MM)
- What is being tested?
- acalabrutinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Feb 2015to 26 Apr 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
United Kingdom2 sites
United Kingdom
Leicester
Guys and St Thomas' Hospital NHS Foundation Trust
London
About this study
Official title: 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)
- Conditions
- Multiple Myeloma (MM)
- Being tested
- acalabrutinib
- Keywords
- Bruton tyrosine kinase inhibitor, Btk, Multiple Myeloma, MM, ACP-196, acalabrutinib, Calquence
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
acalabrutinibDrug
Also called ACP-196
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Acalabrutinib 100 mg twice daily (bid) continuously Receives: Drug: acalabrutinib |
| Cohort 2 | Experimental | Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly Receives: Drug: acalabrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2014 (estimated)
- Study startFeb 2015
- Primary completion26 Apr 2019
- Study completion26 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple Myeloma (MM)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Acerta Pharma BV
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Acerta Pharma, LLC
- Responsible party
- Sponsor
- Investigators
- Acerta Clinical Trials, Study director, 1-888-292-9613
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02211014
- Sponsor's protocol ID
- ACE-MY-001
- Status last verified
- Jul 2020
- First submitted
- 5 Aug 2014
- Last updated
- 31 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Phase 1b Study of ACP-196 With and Without Dexamethasone in Subjects With Multiple Myeloma
- ClinicalTrials.gov ID
- NCT02211014
- Acronym / sponsor ID
- ACE-MY-001
- Conditions
- Multiple Myeloma (MM)
- Keywords
- Bruton tyrosine kinase inhibitor, Btk, Multiple Myeloma, MM, ACP-196, acalabrutinib, Calquence
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Acerta Pharma BVIndustry (pharma, biotech, devices)
- Collaborators
- Acerta Pharma, LLC
- Study start
- Feb 2015 (actual)
- Primary completion
- 26 Apr 2019 (actual)
- Study completion
- 26 Apr 2019 (actual)
- First posted
- 7 Aug 2014 (estimated)
- Results
- Posted 13 May 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To characterize the safety profile of acalabrutinib with and without dexamethasone in subjects with relapsed or refractory Multiple Myeloma (MM)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: acalabrutinibAcalabrutinib 100 mg twice daily (bid) continuously |
| Cohort 2 | Experimental | Drug: acalabrutinibAcalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| acalabrutinibAlso: ACP-196 | Drug | Cohort 1, Cohort 2 |
Primary outcome
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.
3 secondary outcomes
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.
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.
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Acerta Clinical Trials study director
1-888-292-9613
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing acalabrutinib in people with Multiple Myeloma (MM), run by Acerta Pharma BV at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 May 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2020.