Phase 2 Study Adding Pracinostat to a Hypomethylating Agent (HMA) in Patients With MDS Who Failed to Respond to Single Agent HMA
NCT ID: NCT01993641
Last Updated: 2017-02-23
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE2
45 participants
INTERVENTIONAL
2013-12-31
2016-06-30
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Pracinostat added to HMA
Pracinostat in combination with HMA treatment (either azacitidine or decitabine) used in initial single agent treatment for that patient
pracinostat
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
Azacitidine
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)
Decitabine
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.
Interventions
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pracinostat
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
Azacitidine
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)
Decitabine
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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Histologically or cytologically documented diagnosis of MDS (any French-American-British classification \[FAB\] subtype)
3. Bone marrow blasts \>5% and \<30% and a peripheral white blood cell (WBC) count of \<20,000 /µL
4. Bone marrow biopsy, aspirates, and peripheral blood smears within 28 days of first study treatment
5. 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
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)
6. Must have demonstrated tolerability to single agent HMA
7. 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
8. Not a candidate for hematopoietic stem cell transplant within 4 months of screening
9. ECOG performance status of 0, 1, or 2
10. 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
11. Female or male patients ≥18 years-of-age
12. 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.
13. Willingness and ability to understand the nature of this trial and to comply
Exclusion Criteria
* 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
2. Patients who are candidates for aggressive chemotherapy (e.g. typical AML induction therapy)
3. 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
4. Concomitant treatment with agents that have activity against HDAC inhibitors is not permitted
5. Clinical evidence of CNS involvement
6. Patients with gastrointestinal (GI) tract disease, uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis)
7. Active infection with human immunodeficiency virus or chronic hepatitis B or C
8. Life-threatening illness unrelated to cancer or any serious medical or psychiatric illness that could potentially interfere with participation in this study
9. 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
10. Inability or unwillingness (including psychological, familial, sociological, or geographical conditions) to comply
18 Years
ALL
No
Sponsors
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Helsinn Healthcare SA
INDUSTRY
Responsible Party
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Principal Investigators
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Guillermo Garcia-Manero, MD
Role: PRINCIPAL_INVESTIGATOR
M.D. Anderson Cancer Center
Locations
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Southern Cancer Center
Mobile, Alabama, United States
City of Hope
Duarte, California, United States
USC Norris Comprehensive Cancer Center
Los Angeles, California, United States
Sutter Medical Group
Sacramento, California, United States
Colorado Blood Cancer Institute
Denver, Colorado, United States
Yale School of Medicine
New Haven, Connecticut, United States
Florida Cancer Specialist South
Fort Myers, Florida, United States
Florida Cancer Specialist North
St. Petersburg, Florida, United States
Northwestern University
Chicago, Illinois, United States
University of Kansas Cancer Center
Westwood, Kansas, United States
University of Kentucky
Lexington, Kentucky, United States
John Theurer Cancer Center
Hackensak, New Jersey, United States
Oncology Hematology Care
Cincinati, Ohio, United States
Cleveland Clinic
Cleveland, Ohio, United States
University of Oklahoma Health Science Center
Oklahoma City, Oklahoma, United States
Tennessee Oncology-Chattanooga
Chattanooga, Tennessee, United States
Tennessee Oncology
Nashville, Tennessee, United States
Baylor University Medical Center
Dallas, Texas, United States
University of Texas Southwestern
Dallas, Texas, United States
MD Anderson Cancer Center
Houston, Texas, United States
Cancer Care Centers of South Texas
San Antonio, Texas, United States
Countries
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Related Links
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Sponsor website
Other Identifiers
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MEI-005
Identifier Type: -
Identifier Source: org_study_id
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