Multiple MyelomaPhase 1NCT02189343
Phase 1b Study Evaluating ACY-1215 (Ricolinostat) in Combination With Pomalidomide and Dexamethasone in Relapsed or Relapsed-and-Refractory Multiple Myeloma
A Phase 1 study testing ACY-1215 in combination with pomalidomide and dexamethasone in people with Multiple Myeloma, run by Celgene at 3 sites in United States.
Trial summary
To determine the maximum tolerated dose (MTD), if present, and dose schedule of ACY-1215 (ricolinostat) in combination with pomalidomide and low-dose dexamethasone in patients with relapsed-and-refractory multiple myeloma. 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-1215 in combination with pomalidomide and dexamethasone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 3 sitesUnited States
- Study dates
- 15 Sep 2014to 30 Apr 2018
- 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
- Patients meeting all of the following criteria may be enrolled in the study:
- Must be able to understand and voluntarily sign an ICF.
- Must be registered into the mandatory POMALYST Risk Evaluation and Mitigation Strategy (REMS)™ program, and be willing and able to comply with the requirements of the POMALYST REMS™ program (Appendix 9.3).
- Must be ≥ 18 years of age at the time of signing the ICF.
- Must be able to adhere to the study visit schedule and other protocol requirements.
- Must have a documented diagnosis of MM and have relapsed or relapsed and refractory disease. Patients must have received at least 2 lines of prior therapies. Patients must have relapsed after having achieved at least stable disease for at least 1 cycle of treatment to at least 1 prior regimen and then developed PD. Relapsed and relapsed-and-refractory patients must have documented evidence of PD during or within 60 days (measured from the end of the last cycle) of completing treatment with the last antimyeloma drug regimen used just prior to study entry.
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- Patients must have undergone prior treatment with at least 2 cycles of lenalidomide and at least 2 cycles of a proteasome inhibitor (either in a separate regimen or within the same regimen.
- Must not be a candidate for autologous stem cell transplant (ASCT), have declined the option of ASCT, or have relapsed after prior ASCT.
- Must have measurable levels of myeloma paraprotein in serum (≥ 0.5 g/dL) or urine (≥ 0.2 g/24 hours). Patients who do not have myeloma paraprotein must have serum free light chain (SFLC) concentration of ≥ 10 mg/dL, provided SFLC ratio is abnormal. Nonsecretory myeloma is excluded.
- Must have Eastern Cooperative Oncology Group performance status score of 0, 1, or 2.
- Females of childbearing potential must have a negative serum or urine pregnancy test as described in Appendix 9.3 for the POMALYST REMS™ program. Females of childbearing potential and males must either commit to continued abstinence from heterosexual intercourse or must abide by birth control requirements as described in Appendix 9.3 for the POMALYST REMS™ program.
- Must agree to refrain from donating blood while on study drug and for 28 days after discontinuation from this study.
- Must agree not to share study medication with another person.
- Must be able to take ASA (81 or 325 mg) daily as prophylactic anticoagulation. Patients intolerant to ASA may use low molecular weight heparin. Lovenox is recommended. Coumadin will be allowed provided the patient is fully anticoagulated, with an international normalized ratio of 2 to 3.
Who cannot join
- Patients meeting any of the following criteria will be excluded from enrollment in the study:
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the ICF or from following the study requirements.
- Pregnant or lactating females.
- Prior therapy with histone deacetylase inhibitor or pomalidomide.
- Any of the following laboratory abnormalities:
- ANC < 1,000/µL
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- Platelet count < 75,000/ µL for patients in whom < 50% of bone marrow nucleated cells are plasma cells, or a platelet count < 50,000 for patients in whom ≥ 50% of bone marrow nucleated cells are plasma cells
- Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior red blood cell transfusion or recombinant human erythropoietin use is permitted).
- 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.
- Serum glutamic oxaloacetic transaminase/aspartate aminotransferase, or serum glutamic pyruvic transaminase/alanine aminotransferase > 3.0 × ULN
- Serum total bilirubin > 2.0 mg/dL
- Prior history of malignancies, other than MM, unless the patient has been free of the disease for ≥ 3 years. Exceptions include the following:
- Basal or squamous cell carcinoma of the skin
- Ductal carcinoma in situ; or cervical intraepithelial neoplasia
- Carcinoma of the prostate with a current prostate-specific antigen below the upper limit of normal
- Corrected QT interval (QTc) using Fridericia's formula value > 480 msec at Screening; family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy at Screening; previous history of drug-induced QTc prolongation or the need for treatment with medications known or suspected of producing prolonged QTc intervals on electrocardiogram.
- Known human immunodeficiency virus, hepatitis B virus, and known or suspected active hepatitis C virus infection.
- Hypersensitivity to thalidomide, lenalidomide, pomalidomide, or dexamethasone (such as Steven Johnson Syndrome). Hypersensitivity, such as rash, that can be medically managed is allowable.
- Peripheral neuropathy ≥ Grade 2 despite supportive therapy.
- Radiotherapy or systemic therapy (standard or an investigational or biologic anticancer agent) within 14 days of initiation of study drug treatment.
- Current enrollment in another clinical trial involving treatment and/or receiving an investigational agent for any reason.
- Inability or unwillingness to comply with birth control requirements or any of the POMALYST REMS™ requirements per Appendix 9.3.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
UT Southwestern Medical Center Simmons Comprehensive Cancer Center
Dallas, Texas, 75390-8852
University of Utah Huntsman Cancer Institute
Salt Lake City, Utah, 84112
CTRC at The UT Health Science Center at San Antonio
San Antonio, Texas, 78229
About this study
Official title: A Phase 1b Multi-Center, Open Label, Dose-Escalation Study to Determine the Maximum Tolerated Dose, Safety, and Anti-Tumor Activity of an Alternative Liquid Formulation of ACY-1215 (Ricolinostat) In Combination With Pomalidomide and Low-Dose Dexamethasone In Patients With Relapsed and Refractory Multiple Myeloma
To determine the maximum tolerated dose (MTD), if present, and dose schedule of ACY-1215 (ricolinostat) in combination with pomalidomide and low-dose dexamethasone in patients with relapsed-and-refractory multiple myeloma.
Read the detailed description
To determine the maximum tolerated dose (MTD), if present, and to identify a recommended dose and schedule of ricolinostat administered in an alternative liquid formulation (ALF) (10mg/mL) in combination with pomalidomide and low-dose dexamethasone in patients with relapsed or relapsed-and-refractory multiple myeloma.
To evaluate the safety and any anti-tumor activity of ricolinostat administered in combination with pomalidomide and dexamethasone as treatment for patients with relapsed or relapsed-and-refractory multiple myeloma, including duration of response.
To assess the Pharmacokinetics and Pharmacodynamics of all three medications administered in combination, and to assess the Pharmacokinetics of ricolinostat and pomalidomide specifically. An evaluation of the relationship between response and biomarkers relating to interacellular acetylation may also be completed.
- Conditions
- Multiple Myeloma
- Being tested
- ACY-1215 in combination with pomalidomide and dexamethasone
- Keywords
- Multiple Myeloma, Relapsed and Refractory, Refractory Disease, Progressive Disease, Pomalidomide, Dexamethasone, Proteasome Inhibitor, Ricolinostat
- Medical subject headings
- Multiple Myeloma, Recurrence, Disease, Disease Progression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACY-1215 in combination with pomalidomide and dexamethasoneDrug
Also called ACY-1215 (Ricolinostat), Pomalidomide, Dexamethasone
Escalating dose Cohorts to determine a potential Maximum Tolerated Dose to recommend for a dosing schedule.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation Cohort | Experimental | Dose Escalating Cohorts of ACY-1215 in combination with pomalidomide and dexamethasone. Receives: Drug: ACY-1215 in combination with pomalidomide and dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine Maximum Tolerated Dose (MTD) if any, and recommended dose schedule
Identify the MTD of ACY-1215 administered in an alternative liquid formulation (ALF) if present, and identify a recommended dose and schedule. Patients will be followed for completion of 6 28-day Cycles of Study Treatment (for ITT Population analysis).
Measured: Every 56 days on treatment, estimated average of 4 months.
Secondary outcomes (4)
Safety
To assess the type, frequency, and severity of adverse events (AEs) and relationship of AEs to study drug.
Measured: Upon completion of a 28-day treatment cycle and for the duration of treatment, an estimated average of 4 months.
Anti-Tumor Activity
Anti-tumor activity will be measured by objective response to treatment as assessed by the site Investigators using International Myeloma Working Group (IMWG) Uniform Response criteria. Anti-tumor activity will also be measured by duration of response, time to response, and time to progression. The Response rate will be the percentage of patients who achieve PR or better. The number of patients who have at least MR or better will also be collected as clinical benefit response. Progression-free survival (PFS) will be defined as the time from first dose of study treatment to the first documentation of disease progression or death from any cause during the study. For responders, time to tumor response and response duration will be analyzed.
Measured: Upon completion of a 28-day treatment cycle and for the duration of treatment, an estimated average of 4 months.
Pharmacokinetics
Plasma levels of ACY-1215 will be measured to assess the single and multiple dose PK of AC-1215 in combination with pomalidomide and low-dose dexamethasone. Plasma levels of pomalidomide will be measured to assess the PK of pomalidomide in combination with ACY-1215 and low-dose dexamethasone.
Measured: Up to 8 days post first dose
Pharmacodynamics
Exposure response of ACY-1215 in combination with pomalidomide and low-dose dexamethasone, including biomarkers relating to intracellular protein acetylation, protein levels, mRNA and microRA expression profiles.
Measured: Up to 24 hours post first dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2014 (estimated)
- Study start15 Sep 2014
- Primary completion18 Apr 2018
- Study completion30 Apr 2018
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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sumit Madan, MD, Principal investigator, The University of Texas Health Science Center at San Antonio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02189343
- Sponsor's protocol ID
- ACE-MM-104
- Status last verified
- Nov 2019
- First submitted
- 30 May 2014
- Last updated
- 21 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Multi-Center, Open Label, Dose-Escalation Study to Determine the Maximum Tolerated Dose, Safety, and Anti-Tumor Activity of an Alternative Liquid Formulation of ACY-1215 (Ricolinostat) In Combination With Pomalidomide and Low-Dose Dexamethasone In Patients With Relapsed and Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT02189343
- Acronym / sponsor ID
- ACE-MM-104
- Conditions
- Multiple Myeloma
- Keywords
- Multiple Myeloma, Relapsed and Refractory, Refractory Disease, Progressive Disease, Pomalidomide, Dexamethasone, Proteasome Inhibitor, Ricolinostat
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Study start
- 15 Sep 2014 (actual)
- Primary completion
- 18 Apr 2018 (actual)
- Study completion
- 30 Apr 2018 (actual)
- First posted
- 14 Jul 2014 (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.
To determine the maximum tolerated dose (MTD), if present, and dose schedule of ACY-1215 (ricolinostat) in combination with pomalidomide and low-dose dexamethasone in patients with relapsed-and-refractory multiple myeloma.
Detailed description
To determine the maximum tolerated dose (MTD), if present, and to identify a recommended dose and schedule of ricolinostat administered in an alternative liquid formulation (ALF) (10mg/mL) in combination with pomalidomide and low-dose dexamethasone in patients with relapsed or relapsed-and-refractory multiple myeloma.
To evaluate the safety and any anti-tumor activity of ricolinostat administered in combination with pomalidomide and dexamethasone as treatment for patients with relapsed or relapsed-and-refractory multiple myeloma, including duration of response.
To assess the Pharmacokinetics and Pharmacodynamics of all three medications administered in combination, and to assess the Pharmacokinetics of ricolinostat and pomalidomide specifically. An evaluation of the relationship between response and biomarkers relating to interacellular acetylation may also be completed.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation Cohort | Experimental | Drug: ACY-1215 in combination with pomalidomide and dexamethasoneDose Escalating Cohorts of ACY-1215 in combination with pomalidomide and dexamethasone. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Must be able to understand and voluntarily sign an ICF.
- Must be registered into the mandatory POMALYST Risk Evaluation and Mitigation Strategy (REMS)™ program, and be willing and able to comply with the requirements of the POMALYST REMS™ program (Appendix 9.3).
- Must be ≥ 18 years of age at the time of signing the ICF.
- Must be able to adhere to the study visit schedule and other protocol requirements.
- Must have a documented diagnosis of MM and have relapsed or relapsed and refractory disease. Patients must have received at least 2 lines of prior therapies. Patients must have relapsed after having achieved at least stable disease for at least 1 cycle of treatment to at least 1 prior regimen and then developed PD. Relapsed and relapsed-and-refractory patients must have documented evidence of PD during or within 60 days (measured from the end of the last cycle) of completing treatment with the last antimyeloma drug regimen used just prior to study entry.
Key exclusion criteria (22 listed)
- Patients meeting any of the following criteria will be excluded from enrollment in the study:
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the ICF or from following the study requirements.
- Pregnant or lactating females.
- Prior therapy with histone deacetylase inhibitor or pomalidomide.
- Any of the following laboratory abnormalities:
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-1215 in combination with pomalidomide and dexamethasoneAlso: ACY-1215 (Ricolinostat), Pomalidomide, DexamethasoneEscalating dose Cohorts to determine a potential Maximum Tolerated Dose to recommend for a dosing schedule. | Drug | Dose Escalation Cohort |
Primary outcome
Determine Maximum Tolerated Dose (MTD) if any, and recommended dose schedule
Time frame: Every 56 days on treatment, estimated average of 4 months.
Identify the MTD of ACY-1215 administered in an alternative liquid formulation (ALF) if present, and identify a recommended dose and schedule. Patients will be followed for completion of 6 28-day Cycles of Study Treatment (for ITT Population analysis).
4 secondary outcomes
Safety
Time frame: Upon completion of a 28-day treatment cycle and for the duration of treatment, an estimated average of 4 months.
Anti-Tumor Activity
Time frame: Upon completion of a 28-day treatment cycle and for the duration of treatment, an estimated average of 4 months.
Pharmacokinetics
Time frame: Up to 8 days post first dose
Pharmacodynamics
Time frame: Up to 24 hours post first dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2019.
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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.
Sumit Madan, MD principal investigator
The University of Texas Health Science Center at San Antonio
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ACY-1215 in combination with pomalidomide and dexamethasone in people with Multiple Myeloma, run by Celgene at 3 sites in United States.
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 14 inclusion and 22 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 21 Nov 2019. 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 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Determine Maximum Tolerated Dose (MTD) if any, and recommended dose schedule (time frame: Every 56 days on treatment, estimated average of 4 months.). 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 21 Nov 2019; AzTrials last refreshed its copy on 30 Oct 2026.