Overview

This trial is active, not recruiting.

Condition myelodysplastic syndrome
Treatments pracinostat, placebo, azacitidine
Phase phase 2
Target HDAC
Sponsor MEI Pharma, Inc.
Start date June 2013
End date March 2017
Trial size 102 participants
Trial identifier NCT01873703, MEI-003

Summary

The purpose of this randomized, double-blind, placebo-controlled study is to determine the safety and efficacy of pracinostat compared to placebo when combined with azacitidine, and FDA approved treatment for Myelodysplastic Syndrome (MDS).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator)
Primary purpose treatment
Arm
(Experimental)
60 mg of pracinostat by mouth 3 times a week for 3 weeks followed by 1 week of rest repeated every 28 days. 75 mg/m2 Azacitidine for 7 days of each 28 day cycle, via subcutaneous (SC) injection or intravenous infusion if SC injections are intolerable
pracinostat SB939
Histone deacetylase inhibitor (HDACi)
azacitidine Vidaza
Active comparator 75 mg/m2 Azacitidine for 7 days of each 28 day cycle, via subcutaneous (SC) injection or intravenous infusion if SC injections are intolerable
(Placebo Comparator)
Placebo by mouth 3 times a week for 3 weeks followed by 1 week of rest repeated every 28 days. 75 mg/m2 Azacitidine for 7 days of each 28 day cycle, via subcutaneous (SC) injection or intravenous infusion if SC injections are intolerable
placebo
Placebo
azacitidine Vidaza
Active comparator 75 mg/m2 Azacitidine for 7 days of each 28 day cycle, via subcutaneous (SC) injection or intravenous infusion if SC injections are intolerable

Primary Outcomes

Measure
Estimate efficacy
time frame: 6 months

Secondary Outcomes

Measure
Overall response rate
time frame: 6 months
Hematologic Improvement
time frame: 6 months
Duration of response
time frame: 6 months
Progression free survival
time frame: 12 months
Rate of leukemic transformation
time frame: 6 - 24 months
Overall survival
time frame: 6-24 months
AE profile
time frame: 12 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Voluntary written informed consent - Histologically or cytologically documented diagnosis of MDS (any French-American-British [FAB] classification subtype; that is classified as intermediate 2 (1.5 to 2.0 points) or high risk (≥2.5 points) according to the International Prognostic Scoring System risk category, with >5% and <30% blasts, and a peripheral blast count of <20,000 - Bone marrow aspirate smears and bone marrow biopsies within 28 days of first study treatment - There must be a clinical indication for treatment with azacitidine. - Previously untreated with hypomethylating agents (prior therapy with transfusions, hematopoietic growth factors, or immunosuppressive therapy is allowed) - Eastern Cooperative Oncology Group performance status of 0, 1, or 2 - Adequate organ function as evidenced by: 1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x the upper limit of normal (ULN) (≤5 x ULN for patients with hepatic metastases 2. Total bilirubin ≤1.5 x ULN or total bilirubin of 2, whichever is higher 3. Serum creatinine <2 mg/dL, or creatinine clearance ≤1.5 x ULN 4. QTcF interval ≤470 msec - Female or male patients ≥18 years-of-age - Male patients who are surgically sterile or willing to use adequate contraceptive measures or abstain from heterosexual intercourse during the entire study treatment period - Female patients who are surgically sterile or post menopausal or female patients who are not of child-bearing potential and female patients of child-bearing potential who agree to use adequate contraceptive measures or abstain from intercourse during the study treatment period, who are not breastfeeding, and who have had a negative serum pregnancy test ≤7 days prior to first study treatment. - Willingness and ability to comply with the trial and follow-up procedures Exclusion Criteria: - Received any of the following within the specified time frame prior to administration of study medication: 1. Any investigational agent within 14 days or 5 half-lives prior to first study treatment, whichever is longer 2. Previous therapy for malignancy within 21 days prior to first study treatment, including any chemotherapy, immunotherapy, biological or hormonal therapy (6 weeks for nitrosoureas or mitomycin C) 3. Hydroxyurea within 48 hours prior to first study treatment 4. Hematopoietic growth factors: erythropoietin, granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), or thrombopoietin receptor agonists at least 7 days (14 days for Aranesp) prior to study enrollment 5. Major surgery within 4 weeks prior to first study treatment - Patients that have not recovered from side effects of previous therapy - Cardiopulmonary function exclusion: 1. Current unstable arrhythmia requiring treatment 2. History of symptomatic congestive heart failure (New York Heart Association Classes III or IV) 3. History of myocardial infarction within 6 months of enrollment 4. Current unstable angina - Concomitant treatment with histone deacetylase (HDAC) inhibitors or drugs with significant action as HDAC inhibitors, such as valproic acid, is not permitted - Clinical evidence of central nervous system involvement - Patients with gastrointestinal (GI) tract disease, causing the inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis). - Active infection with HIV or chronic hepatitis B or C - Life-threatening illness unrelated to cancer, or any serious medical or psychiatric illness that could, in the investigator's opinion, 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 - Inability (including psychological, familial, sociological, or geographical conditions) to comply with trial and/or follow-up procedures

Additional Information

Official title A Phase 2 Randomized Double-Blind Placebo-Controlled Study of Pracinostat in Combination With Azacitidine in Patients With Previously Untreated International Prognostic Scoring System (IPSS) Intermediate Risk-2 or High-Risk Myelodysplastic Syndrome (MDS)
Principal investigator Guillermo Garcia-Manero, MD
Trial information was received from ClinicalTrials.gov and was last updated in April 2016.
Information provided to ClinicalTrials.gov by MEI Pharma, Inc..