Multiple MyelomaPhase 1NCT02400242
Study of ACY-241 Alone and in Combination With Pomalidomide and Dexamethasone in Multiple Myeloma
A Phase 1 study testing ACY-241, Pomalidomide and Dexamethasone in people with Multiple Myeloma, run by Celgene at 17 sites in 5 countries.
Trial summary
This is a phase 1a/1b, multicenter, single-arm, open-label, dose escalation study to determine the maximum tolerated dose (MTD) and evaluate the safety and preliminary antitumor activity of ACY-241 for oral administration as monotherapy and in combination therapy with orally administered pomalidomide and low-dose… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- ACY-241, Pomalidomide and Dexamethasone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 85 participants
- Where
- 17 sitesin 5 countries
- Study dates
- 7 May 2015to 3 Jun 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Must have a documented diagnosis of MM and have relapsed or relapsed-and-refractory disease. All patients must have relapsed after having achieved at least stable disease (SD) for at least 1 cycle of treatment to at least 1 prior regimen and then developed progressive disease (PD). Relapsed-and-refractory patients also have documented evidence of PD during or within 60 days of completing last treatment
- Must have undergone prior treatment with at least 2 cycles of lenalidomide and at least 2 cycles of proteasome inhibitor unless not a candidate.
- May have undergone prior treatment with pomalidomide if patient is not refractory to pomalidomide and has previously achieved a response of MR or better to pomalidomide.
- Must have measurable disease (serum M-protein or urine M-protein).
- Must have Eastern Cooperative Oncology Group (ECOG) Performance score of 0, 1, or 2.
- Must be able to take low-dose aspirin, low molecular weight heparin, or other equivalent antithrombotic or anticoagulant daily as prophylactic anticoagulation.
Who cannot join
- Prior therapy with pomalidomide with best response of PD or SD.
- Prior therapy with histone deacetylase (HDAC) inhibitor.
- Any of the following laboratory abnormalities: Absolute neutrophil count(ANC) < 1,000/µL, Platelet count < 75,000/µL or < 50,000/µL for patients in whom ≥ 50% of bone marrow nucleated cells are plasma cells, Hemoglobin < 8 g/dL, Creatinine clearance < 45 mL/min according to Cockcroft-Gault formula. If creatinine clearance calculated from the 24 hour urine sample is ≥ 45 mL/min, patient will qualify for the trial, Aspartate transaminase (AST) or Alanine transaminase (ALT) > 3.0 × Upper Limited Normal (ULN), Serum total bilirubin > 2.0 mg/dL or > 3.0 × ULN for patients with hereditary benign hyperbilirubinaemia.
- Hematologic growth factors are not allowed at screening or during the first cycle of phase 1a or 1b.
- Nonsecretory myeloma or free light chain detected in serum only (ogliosecretory).
- Hypersensitivity to thalidomide, lenalidomide, pomalidomide, or dexamethasone
- Patients who received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant less than 12 months prior to initiation of study
Trial locations and contacts
17 sites in 5 countries.
17 sites in 5 countries
United States11 sites
Local Institution - 103
Atlanta, Georgia, 30322
Local Institution - 104
Boston, Massachusetts, 02114
Local Institution - 105
Boston, Massachusetts, 02215
Gabrail Cancer Center Research
Canton, Ohio, 44718
Colorado Blood Cancer Institute
Denver, Colorado, 80218
University of Miami Medical Center
Miami, Florida, 33136-2107
Local Institution - 101
New York, New York, 10065
CTRC at The UT Health Science Center at San Antonio
San Antonio, Texas, 78229
Local Institution - 111
Seattle, Washington, 98104
Local Institution - 108
Tampa, Florida, 33612
Local Institution - 109
Tucson, Arizona, 85719
France2 sites
Local Institution - 340
Lille, 59037
Local Institution - 341
Nantes, 44093
Spain2 sites
Local Institution - 301
Pamplona, 31008
Local Institution - 300
Salamanca, 37007
About this study
Official title: A Phase 1a/1b Multicenter, Single-Arm, Open-Label, Dose-Escalation Study to Determine the Maximum Tolerated Dose, Safety, and Preliminary Activity of Oral ACY-241 Alone and in Combination With Pomalidomide and Low-Dose Dexamethasone in Patients With Relapsed or Relapsed-and-Refractory Multiple Myeloma
This is a phase 1a/1b, multicenter, single-arm, open-label, dose escalation study to determine the maximum tolerated dose (MTD) and evaluate the safety and preliminary antitumor activity of ACY-241 for oral administration as monotherapy and in combination therapy with orally administered pomalidomide and low-dose dexamethasone in eligible patients with relapsed or relapsed-and-refractory multiple myeloma (MM).
Read the detailed description
During phase 1a, patients will receive 1 cycle of ACY-241 monotherapy. Patients who complete the ACY-241 monotherapy cycle without a dose limiting toxicity (DLT) and are clinically stable may continue to phase 1b combination therapy, beginning with Cycle 2. During phase 1b, patients will receive ACY 241 in combination with pomalidomide and low dose dexamethasone at the currently approved pomalidomide dose and schedule. Each cohort of patients in phase 1a and phase 1b will consist of at least 3 patients. The first patient enrolled in each cohort of phase 1a will be observed for 1 week before enrollment of subsequent patients in the cohort. Patients who withdraw consent before entering phase 1b will be replaced. (Replacement patients must complete phase 1a prior to continuing to phase 1b.) Patients who experience a DLT or other unacceptable toxicity in Cycle 1 of phase 1a monotherapy or Cycle 2, the first cycle of phase 1b combination therapy, will be removed from study treatment. An assessment of the safety of treatment will be completed by the Safety Review Committee (SRC) prior to dose-escalation.
- Conditions
- Multiple Myeloma
- Being tested
- ACY-241, Pomalidomide, Dexamethasone
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACY-241Drug
Also called Histone deacetylase inhibitor
Dose escalation up to 480 mg administered orally on Days 1-21 of a 28 day cycle.
PomalidomideDrug
Also called immunomodulatory agent
4 mg qd dosed on days 1-21 of a 28 day cycle
DexamethasoneDrug
Also called corticosteriod
40 mg qd on days 1, 8, 15, 22
| Study group | Role | What they receive |
|---|---|---|
| ACY-241, Pomalidomide, and dexamethasone | Experimental | Open label dosing cohorts will evaluate oral ACY-241 (dosing ranging from 180 mg to 480 mg days 1-21) in combination with oral pomalidomide (4 mg days 1-21), and oral dexamethasone (40 mg qd on days 1, 8, 15, 22). Receives: Drug: ACY-241; Drug: Pomalidomide; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of ACY-241 as monotherapy as assessed by dose limiting toxicities
Measured: Cycle 1 (28 days)
Maximum tolerated dose of ACY-241 in combination with pomalidomide and low dose dexamethasone as assessed by dose limiting toxicities
First cycle of combination therapy
Measured: Cycle 2 (28 days)
Secondary outcomes (12)
Frequency and severity of AEs as measured by safety and tolerability
Measured: Cycle 1 (28 days)
Single- and multiple-dose peak-plasma concentration
Measured: Cycle 1 days 1, 2, 15 and 16
Single- and multiple-dose area under the plasma concentration versus time curve
Measured: Cycle 1 days 1, 2, 15 and 16
Change in acetylation of histone and tubulin as a measure of pharmacodynamics
Measured: Cycles 1 days 1, 2, 15, 16 and 22
Change in fetal hemoglobin expression as a measure of pharmacodynamics
Measured: Cycles 1 days 1, 2, 15, 16 and 22
ACY-241 metabolite concentration in blood samples
Measured: Cycles 1 days 1, 2, 15, 16 and 22
Exposure response analyses of potential biomarkers of response.
Measured: Cycles 1 days 1, 2, 15, 16 and 22
Frequency and severity of AEs as measured by safety and tolerability in combination
Measured: Beginning at Cycle 2 (28 day cycle each) until end of treatment
Change in fetal hemoglobin expression as a measure of pharmacodynamics
Measured: Cycle 2 days 1, 2, 15, 16 and 22
Change in acetylation of histone and tubulin as a measure of pharmacodynamics
Measured: Cycle 2 days 1, 2, 15, 16 and 22
Single- and multiple-dose area under the plasma concentration versus time curve
Measured: Cycle 2 days 1, 2, 15, and 16
Quantification of M-protein as a measure of anti-tumor activity
Measured: Day 1 of each cycle beginning at Cycle 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2015 (estimated)
- Study start7 May 2015
- Primary completion3 Jun 2024
- Study completion3 Jun 2024
Why it stopped: Lack of efficacy
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by CelgeneThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02400242
- Sponsor's protocol ID
- ACE-MM-200
- Status last verified
- Jul 2024
- First submitted
- 3 Mar 2015
- Last updated
- 9 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1a/1b Multicenter, Single-Arm, Open-Label, Dose-Escalation Study to Determine the Maximum Tolerated Dose, Safety, and Preliminary Activity of Oral ACY-241 Alone and in Combination With Pomalidomide and Low-Dose Dexamethasone in Patients With Relapsed or Relapsed-and-Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT02400242
- Acronym / sponsor ID
- ACE-MM-200
- Conditions
- Multiple Myeloma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of efficacy
- Enrolment
- 85 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Study start
- 7 May 2015 (actual)
- Primary completion
- 3 Jun 2024 (actual)
- Study completion
- 3 Jun 2024 (actual)
- First posted
- 27 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase 1a/1b, multicenter, single-arm, open-label, dose escalation study to determine the maximum tolerated dose (MTD) and evaluate the safety and preliminary antitumor activity of ACY-241 for oral administration as monotherapy and in combination therapy with orally administered pomalidomide and low-dose dexamethasone in eligible patients with relapsed or relapsed-and-refractory multiple myeloma (MM).
Detailed description
During phase 1a, patients will receive 1 cycle of ACY-241 monotherapy. Patients who complete the ACY-241 monotherapy cycle without a dose limiting toxicity (DLT) and are clinically stable may continue to phase 1b combination therapy, beginning with Cycle 2. During phase 1b, patients will receive ACY 241 in combination with pomalidomide and low dose dexamethasone at the currently approved pomalidomide dose and schedule. Each cohort of patients in phase 1a and phase 1b will consist of at least 3 patients. The first patient enrolled in each cohort of phase 1a will be observed for 1 week before enrollment of subsequent patients in the cohort. Patients who withdraw consent before entering phase 1b will be replaced. (Replacement patients must complete phase 1a prior to continuing to phase 1b.) Patients who experience a DLT or other unacceptable toxicity in Cycle 1 of phase 1a monotherapy or Cycle 2, the first cycle of phase 1b combination therapy, will be removed from study treatment. An assessment of the safety of treatment will be completed by the Safety Review Committee (SRC) prior to dose-escalation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ACY-241, Pomalidomide, and dexamethasone | Experimental | Drug: ACY-241, Drug: Pomalidomide, Drug: DexamethasoneOpen label dosing cohorts will evaluate oral ACY-241 (dosing ranging from 180 mg to 480 mg days 1-21) in combination with oral pomalidomide (4 mg days 1-21), and oral dexamethasone (40 mg qd on days 1, 8, 15, 22). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Must have a documented diagnosis of MM and have relapsed or relapsed-and-refractory disease. All patients must have relapsed after having achieved at least stable disease (SD) for at least 1 cycle of treatment to at least 1 prior regimen and then developed progressive disease (PD). Relapsed-and-refractory patients also have documented evidence of PD during or within 60 days of completing last treatment
- Must have undergone prior treatment with at least 2 cycles of lenalidomide and at least 2 cycles of proteasome inhibitor unless not a candidate.
- May have undergone prior treatment with pomalidomide if patient is not refractory to pomalidomide and has previously achieved a response of MR or better to pomalidomide.
- Must have measurable disease (serum M-protein or urine M-protein).
- Must have Eastern Cooperative Oncology Group (ECOG) Performance score of 0, 1, or 2.
Key exclusion criteria (7 listed)
- Prior therapy with pomalidomide with best response of PD or SD.
- Prior therapy with histone deacetylase (HDAC) inhibitor.
- Any of the following laboratory abnormalities: Absolute neutrophil count(ANC) < 1,000/µL, Platelet count < 75,000/µL or < 50,000/µL for patients in whom ≥ 50% of bone marrow nucleated cells are plasma cells, Hemoglobin < 8 g/dL, Creatinine clearance < 45 mL/min according to Cockcroft-Gault formula. If creatinine clearance calculated from the 24 hour urine sample is ≥ 45 mL/min, patient will qualify for the trial, Aspartate transaminase (AST) or Alanine transaminase (ALT) > 3.0 × Upper Limited Normal (ULN), Serum total bilirubin > 2.0 mg/dL or > 3.0 × ULN for patients with hereditary benign hyperbilirubinaemia.
- Hematologic growth factors are not allowed at screening or during the first cycle of phase 1a or 1b.
- Nonsecretory myeloma or free light chain detected in serum only (ogliosecretory).
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 |
|---|---|---|
| ACY-241Also: Histone deacetylase inhibitorDose escalation up to 480 mg administered orally on Days 1-21 of a 28 day cycle. | Drug | ACY-241, Pomalidomide, and dexamethasone |
| PomalidomideAlso: immunomodulatory agent4 mg qd dosed on days 1-21 of a 28 day cycle | Drug | ACY-241, Pomalidomide, and dexamethasone |
| DexamethasoneAlso: corticosteriod40 mg qd on days 1, 8, 15, 22 | Drug | ACY-241, Pomalidomide, and dexamethasone |
Primary outcome
Maximum tolerated dose of ACY-241 as monotherapy as assessed by dose limiting toxicities
Time frame: Cycle 1 (28 days)
Maximum tolerated dose of ACY-241 in combination with pomalidomide and low dose dexamethasone as assessed by dose limiting toxicities
Time frame: Cycle 2 (28 days)
First cycle of combination therapy
12 secondary outcomes
Frequency and severity of AEs as measured by safety and tolerability
Time frame: Cycle 1 (28 days)
Single- and multiple-dose peak-plasma concentration
Time frame: Cycle 1 days 1, 2, 15 and 16
Single- and multiple-dose area under the plasma concentration versus time curve
Time frame: Cycle 1 days 1, 2, 15 and 16
Change in acetylation of histone and tubulin as a measure of pharmacodynamics
Time frame: Cycles 1 days 1, 2, 15, 16 and 22
Change in fetal hemoglobin expression as a measure of pharmacodynamics
Time frame: Cycles 1 days 1, 2, 15, 16 and 22
ACY-241 metabolite concentration in blood samples
Time frame: Cycles 1 days 1, 2, 15, 16 and 22
Exposure response analyses of potential biomarkers of response.
Time frame: Cycles 1 days 1, 2, 15, 16 and 22
Frequency and severity of AEs as measured by safety and tolerability in combination
Time frame: Beginning at Cycle 2 (28 day cycle each) until end of treatment
Change in fetal hemoglobin expression as a measure of pharmacodynamics
Time frame: Cycle 2 days 1, 2, 15, 16 and 22
Change in acetylation of histone and tubulin as a measure of pharmacodynamics
Time frame: Cycle 2 days 1, 2, 15, 16 and 22
Single- and multiple-dose area under the plasma concentration versus time curve
Time frame: Cycle 2 days 1, 2, 15, and 16
Quantification of M-protein as a measure of anti-tumor activity
Time frame: Day 1 of each cycle beginning at Cycle 2
Results and safety
The study was stopped early (reason given: Lack of efficacy). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2024.
- BMS Clinical Trial InformationLink provided by the sponsor.
Related trials for Multiple Myeloma
Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Active, not recruitingPhase 3
A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)
Multiple Myeloma
Active, not recruitingPhase 1/2
A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment
Multiple Myeloma
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
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.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
17 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ACY-241, Pomalidomide and Dexamethasone in people with Multiple Myeloma, run by Celgene at 17 sites in 5 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 6 inclusion and 7 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: stopped early, as of the sponsor's last update on 9 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, France, Spain, Germany, Greece. 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?
The study was stopped early (reason given: Lack of efficacy). Results are not available in the source record.
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?
Maximum tolerated dose of ACY-241 as monotherapy as assessed by dose limiting toxicities (time frame: Cycle 1 (28 days)). The study lists 2 primary outcomes in all. 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 9 Jul 2024.