Myelodysplastic SyndromePhase 2MEI-005NCT01993641
Phase 2 Study Adding Pracinostat to a Hypomethylating Agent (HMA) in Patients With MDS Who Failed to Respond to Single Agent HMA
A Phase 2 study testing pracinostat, Azacitidine and Decitabine in people with Myelodysplastic Syndrome and MDS, run by Helsinn Healthcare SA at 21 sites in United States.
Trial summary
The purpose of this open label study is to determine whether combining pracinostat (study drug) with Vidaza (azacitidine) or Dacogen (decitabine) will improve clinical responses in Myelodysplastic Syndrome (MDS) patients who have failed an initial single agent hypomethylating agent (HMA), and to provide additional… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndrome, MDS
- What is being tested?
- pracinostat, Azacitidine and Decitabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 21 sitesUnited States
- Study dates
- Dec 2013to Jun 2016
- Phase
- Phase 2
- 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
- Voluntary written informed consent
- Histologically or cytologically documented diagnosis of MDS (any French-American-British classification [FAB] subtype)
- Bone marrow blasts >5% and <30% and a peripheral white blood cell (WBC) count of <20,000 /µL
- Bone marrow biopsy, aspirates, and peripheral blood smears within 28 days of first study treatment
- Group 1:
- Primary failures: Progression after their most recent HMA therapy according to IWG criteria after receiving single agent azacitidine and/or single agent decitabine, or has worsening cytopenias (increased transfusion requirement), increased BM blasts, progression to a higher FAB type, or develops additional clinically significant cytogenetic abnormalities; Secondary failures: Relapse after any initial CR, PR, HI, or development of clinically significant cytogenetic abnormalities at any time according to IWG criteria after receiving single agent azacitidine or decitabine
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- Group 2:
- Failure to achieve a response (any CR, PR or HI) according to IWG criteria definition of stable disease after the most recent HMA therapy (at least 6 cycles of azacitidine or 4 cycles of decitabine)
- Must have demonstrated tolerability to single agent HMA
- Able to start combination therapy within 3 months of the last single agent HMA dose with no other therapy for disease under study received during this interval
- Not a candidate for hematopoietic stem cell transplant within 4 months of screening
- ECOG performance status of 0, 1, or 2
- Adequate organ function as evidenced by:
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x the upper limit of normal (ULN)
- Total bilirubin ≤1.5 x ULN or total bilirubin of ≤2 mg/dL, whichever is higher
- Serum creatinine <2 mg/dL, or creatinine clearance ≥60 mL/min
- QTcF interval ≤470 msec
- Female or male patients ≥18 years-of-age
- Male patients with female partners are required to use two forms of acceptable contraception; Female patients of childbearing potential must have a negative pregnancy test ≤7 days before first study treatment.
- Willingness and ability to understand the nature of this trial and to comply
Who cannot join
- Received any of the following within the specified time frame after the last single agent HMA dose until the first administration of study medication:
- Any therapy for malignancy between the time of single agent HMA and first on-study treatment
- Hydroxyurea within 48 hours prior to first study treatment
- Hematopoietic growth factors: erythropoietin, granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), or thrombopoietin receptor agonists within 7 days (14 days for Aranesp) prior to first study treatment
- Major surgery within 28 days of study day 1
- Patients who are candidates for aggressive chemotherapy (e.g. typical AML induction therapy)
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- Cardiopulmonary function criteria:
- Current unstable arrhythmia requiring treatment
- History of symptomatic congestive heart failure (New York Heart Association Class III or IV)
- History of myocardial infarction within 6 months of enrollment
- Current unstable angina
- Concomitant treatment with agents that have activity against HDAC inhibitors is not permitted
- Clinical evidence of CNS involvement
- Patients with gastrointestinal (GI) tract disease, uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis)
- Active infection with human immunodeficiency virus or chronic hepatitis B or C
- Life-threatening illness unrelated to cancer or any serious medical or psychiatric illness that could potentially interfere with participation in this study
- Presence of a malignant disease within the last 12 months, with the exception of adequately treated in-situ carcinomas, basal or squamous cell carcinoma, or non-melanomatous skin cancer and other concurrent malignancies will be considered on a case by case basis
- Inability or unwillingness (including psychological, familial, sociological, or geographical conditions) to comply
Trial locations and contacts
21 sites in 1 country.
21 sites in 1 country
United States21 sites
Tennessee Oncology-Chattanooga
Chattanooga, Tennessee, 37404
Northwestern University
Chicago, Illinois, 60601
Oncology Hematology Care
Cincinati, Ohio, 45242
Cleveland Clinic
Cleveland, Ohio, 44195
Baylor University Medical Center
Dallas, Texas, 75246
University of Texas Southwestern
Dallas, Texas, 75390
Colorado Blood Cancer Institute
Denver, Colorado, 80218
City of Hope
Duarte, California, 91010
Florida Cancer Specialist South
Fort Myers, Florida, 33916
John Theurer Cancer Center
Hackensak, New Jersey, 07601
MD Anderson Cancer Center
Houston, Texas, 77030
University of Kentucky
Lexington, Kentucky, 40536
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Southern Cancer Center
Mobile, Alabama, 36608
Tennessee Oncology
Nashville, Tennessee, 37203
Yale School of Medicine
New Haven, Connecticut, 06520
University of Oklahoma Health Science Center
Oklahoma City, Oklahoma, 73104
Sutter Medical Group
Sacramento, California, 95816
Cancer Care Centers of South Texas
San Antonio, Texas, 78229
Florida Cancer Specialist North
St. Petersburg, Florida, 33705
University of Kansas Cancer Center
Westwood, Kansas, 66205
About this study
Official title: A Phase II Simon Two-Stage Study of the Addition of Pracinostat to a Hypomethylating Agent (HMA) in Patients With Myelodysplastic Syndrome (MDS) Who Have Failed to Respond or Maintain a Response to the HMA Alone
The purpose of this open label study is to determine whether combining pracinostat (study drug) with Vidaza (azacitidine) or Dacogen (decitabine) will improve clinical responses in Myelodysplastic Syndrome (MDS) patients who have failed an initial single agent hypomethylating agent (HMA), and to provide additional safety and efficacy data.
- Conditions
- Myelodysplastic Syndrome, MDS
- Being tested
- pracinostat, Azacitidine, Decitabine
- Keywords
- Myelodysplastic Syndrome, MDS, pracinostat, Hypomethylating Agent, HMA, azacitadine, Vidaza, decitabine, dacogen
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pracinostatDrug
Also called SB939
Histone deacetylase inhibitor (HDACi) Pracinostat is to be taken before HMA administration 3 times/week (e.g., Monday, Wednesday, and Friday) for 3 weeks, followed by 1 week of rest as a 28-day cycle. Pracinostat administration will be at the clinic on Day 1 of Cycles 1 and 2 and subject will self-administer at home on all other days
AzacitidineDrug
Also called Vidaza
All patients will receive the dose and schedule of azacitadine to which they previously failed to respond. (e.g. 75 mg/m2 via subcutaneous (SC) injection or intravenous infusion if SC injections are intolerable; 7 days of each 28 day cycle, either Days 1-7, or Days 1-5, rest on Days 6-7, and azacitadine dosing on Days 8-9)
DecitabineDrug
Also called Dacogen
All patients will receive the dose and schedule of decitabine to which they previously failed to respond. Common 28 day treatment regimens include: 20 mg/m2 IV for either 5 or 10 days of each 28-day cycle, 10 mg/m2 given intravenously daily for first 10 days of each 28 day cycle, or 20 mg/m2 given subcutaneously daily for the first 5 days of each 28 day cycle.
The 6-week regimen utilizes a dose of 15 mg/m2 by continuous intravenous infusion over 3 hours repeated every 8 hours for 3 days repeated every 6 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Pracinostat added to HMA | Experimental | Pracinostat in combination with HMA treatment (either azacitidine or decitabine) used in initial single agent treatment for that patient Receives: Drug: pracinostat; Drug: Azacitidine; Drug: Decitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Estimate clinical improvement
Clinical Improvement Rate defined as the proportion of patients with CR, Marrow CR, PR, and HI.
Measured: 6 months
Secondary outcomes (12)
Estimate Overall Response Rate (ORR), including all Complete and Partial Responses, Marrow CR, HI, SD, transfusion independence, and cytogenetic responses
Overall Response Rate (ORR), defined as the proportion of patients with CR, PR, Marrow CR, HI, SD, transfusion independence, and cytogenetic responses according to the IWG criteria
Measured: 6 months
Estimate Complete Response (CR) rate
Complete response (CR) rate, defined as the proportion of patients with a confirmed CR (i.e., confirmed by a CBC at least 4 weeks after CR) according to the IWG criteria
Measured: 6 months
Estimate Hematologic Improvement (HI) rate
Hematologic improvement (HI) rate, defined as the proportion of patients who demonstrate major hematologic improvement as defined by the IWG criteria. Only patients with pre-treatment abnormal values will be considered for this endpoint at 8 weeks.
Measured: 6 months
Estimate Duration of Response (DoR)
Duration of Response (for patients who have achieved CR, PR, or HI), defined as the time from the initial determination of response to the time of disease progression or death on study, whichever occurs first. For patients who are alive and have not experienced disease progression on study (prior to receiving subsequent/new treatment or stem cell transplant), duration of response will be censored at the day of the last adequate disease assessment.
Measured: 6 months
Estimate Progression Free Survival (PFS)
Progression-Free survival (PFS), defined as the time from first day of study drug administration (Day 1) to either disease progression or death. Patients who have not progressed or are alive will be censored at the date of last adequate disease assessment
Measured: 6-12 months
Estimate Event Free Survival (EFS)
Event Free Survival (EFS) defined as the time from first day of study drug administration (Day 1) to failure or death from any cause according to the IWG response criteria. Patients who have not progressed, are alive or died without progression will be censored at the date of last adequate disease assessment
Measured: 12 months
Estimate Overall Survival (OS)
Overall Survival (OS), defined as the time from the first day of study drug administration (Day 1) to death on study. Patients who are alive will be censored at the date last known alive.
Measured: 6-24 months
Assess the safety profile of the combination
Assess the adverse event (AE) profile of pracinostat combined with either azacitidine or decitabine by clinical review of safety events by grade, relationship and event outcomes.
Measured: 12 months
Estimate Marrow CR rate
Marrow CR rate, defined as bone marrow <5% myeloblasts and decrease by > 50% over pretreatment according to IWG criteria.
Measured: 6 months
Assess transfusion independence
Transfusion independence, defined as during the treatment period the patient had no RBC transfusions during any 56 consecutive days or more.
Measured: 6 months
Estimate Stable Disease (SD) rate
Stable disease rate defined as failure to achieve at least a PR, but no evidence of progression for > 8 weeks according to IWG criteria.
Measured: 6 months
Estimate Cytogenetic Response rate
Cytogenetic response rate, defined as complete disappearance of the chromosomal abnormality without appearance of new abnormalities, or partial response of at least 50% reduction of the chromosomal abnormality according to IWG criteria.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2013 (estimated)
- Study startDec 2013
- Primary completionMay 2015
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic SyndromeStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Helsinn Healthcare SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Guillermo Garcia-Manero, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01993641
- Sponsor's protocol ID
- MEI-005
- Acronym
- MEI-005
- Status last verified
- Feb 2017
- First submitted
- 14 Nov 2013
- Last updated
- 23 Feb 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Simon Two-Stage Study of the Addition of Pracinostat to a Hypomethylating Agent (HMA) in Patients With Myelodysplastic Syndrome (MDS) Who Have Failed to Respond or Maintain a Response to the HMA Alone
- ClinicalTrials.gov ID
- NCT01993641
- Acronym / sponsor ID
- MEI-005 / MEI-005
- Conditions
- Myelodysplastic Syndrome, MDS
- Keywords
- Myelodysplastic Syndrome, MDS, pracinostat, Hypomethylating Agent, HMA, azacitadine, Vidaza, decitabine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Helsinn Healthcare SAIndustry (pharma, biotech, devices)
- Study start
- Dec 2013
- Primary completion
- May 2015 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 25 Nov 2013 (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.
The purpose of this open label study is to determine whether combining pracinostat (study drug) with Vidaza (azacitidine) or Dacogen (decitabine) will improve clinical responses in Myelodysplastic Syndrome (MDS) patients who have failed an initial single agent hypomethylating agent (HMA), and to provide additional safety and efficacy data.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pracinostat added to HMA | Experimental | Drug: pracinostat, Drug: Azacitidine, Drug: DecitabinePracinostat in combination with HMA treatment (either azacitidine or decitabine) used in initial single agent treatment for that patient |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Voluntary written informed consent
- Histologically or cytologically documented diagnosis of MDS (any French-American-British classification [FAB] subtype)
- Bone marrow blasts >5% and <30% and a peripheral white blood cell (WBC) count of <20,000 /µL
- Bone marrow biopsy, aspirates, and peripheral blood smears within 28 days of first study treatment
- Group 1:
Key exclusion criteria (18 listed)
- Received any of the following within the specified time frame after the last single agent HMA dose until the first administration of study medication:
- Patients who are candidates for aggressive chemotherapy (e.g. typical AML induction therapy)
- Cardiopulmonary function criteria:
- Concomitant treatment with agents that have activity against HDAC inhibitors is not permitted
- Clinical evidence of CNS involvement
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 |
|---|---|---|
| pracinostatAlso: SB939Histone deacetylase inhibitor (HDACi) Pracinostat is to be taken before HMA administration 3 times/week (e.g., Monday, Wednesday, and Friday) for 3 weeks, followed by 1 week of rest as a 28-day cycle. Pracinostat administration will be at the clinic on Day 1 of Cycles 1 and 2 and subject will self-administer at home on all other days | Drug | Pracinostat added to HMA |
| AzacitidineAlso: VidazaAll patients will receive the dose and schedule of azacitadine to which they previously failed to respond. (e.g. 75 mg/m2 via subcutaneous (SC) injection or intravenous infusion if SC injections are intolerable; 7 days of each 28 day cycle, either Days 1-7, or Days 1-5, rest on Days 6-7, and azacitadine dosing on Days 8-9) | Drug | Pracinostat added to HMA |
| DecitabineAlso: DacogenAll patients will receive the dose and schedule of decitabine to which they previously failed to respond. Common 28 day treatment regimens include: 20 mg/m2 IV for either 5 or 10 days of each 28-day cycle, 10 mg/m2 given intravenously daily for first 10 days of each 28 day cycle, or 20 mg/m2 given subcutaneously daily for the first 5 days of each 28 day cycle. The 6-week regimen utilizes a dose of 15 mg/m2 by continuous intravenous infusion over 3 hours repeated every 8 hours for 3 days repeated every 6 weeks. | Drug | Pracinostat added to HMA |
Primary outcome
Estimate clinical improvement
Time frame: 6 months
Clinical Improvement Rate defined as the proportion of patients with CR, Marrow CR, PR, and HI.
12 secondary outcomes
Estimate Overall Response Rate (ORR), including all Complete and Partial Responses, Marrow CR, HI, SD, transfusion independence, and cytogenetic responses
Time frame: 6 months
Estimate Complete Response (CR) rate
Time frame: 6 months
Estimate Hematologic Improvement (HI) rate
Time frame: 6 months
Estimate Duration of Response (DoR)
Time frame: 6 months
Estimate Progression Free Survival (PFS)
Time frame: 6-12 months
Estimate Event Free Survival (EFS)
Time frame: 12 months
Estimate Overall Survival (OS)
Time frame: 6-24 months
Assess the safety profile of the combination
Time frame: 12 months
Estimate Marrow CR rate
Time frame: 6 months
Assess transfusion independence
Time frame: 6 months
Estimate Stable Disease (SD) rate
Time frame: 6 months
Estimate Cytogenetic Response rate
Time frame: 6 months
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 23 Feb 2017.
- Sponsor websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes
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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.
Guillermo Garcia-Manero, MD principal investigator
M.D. Anderson Cancer Center
21 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing pracinostat, Azacitidine and Decitabine in people with Myelodysplastic Syndrome and MDS, run by Helsinn Healthcare SA at 21 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 20 inclusion and 18 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 23 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Estimate clinical improvement (time frame: 6 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 23 Feb 2017.