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)
Overview
- Phase
- Phase 2
- Intervention
- pracinostat
- Conditions
- Myelodysplastic Syndrome
- Sponsor
- Helsinn Healthcare SA
- Enrollment
- 102
- Locations
- 24
- Primary Endpoint
- Estimate efficacy
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief 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).
Investigators
Eligibility Criteria
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:
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x the upper limit of normal (ULN) (≤5 x ULN for patients with hepatic metastases
- •Total bilirubin ≤1.5 x ULN or total bilirubin of 2, whichever is higher
- •Serum creatinine \<2 mg/dL, or creatinine clearance ≤1.5 x ULN
Exclusion Criteria
- •Received any of the following within the specified time frame prior to administration of study medication:
- •Any investigational agent within 14 days or 5 half-lives prior to first study treatment, whichever is longer
- •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)
- •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 at least 7 days (14 days for Aranesp) prior to study enrollment
- •Major surgery within 4 weeks prior to first study treatment
- •Patients that have not recovered from side effects of previous therapy
- •Cardiopulmonary function exclusion:
- •Current unstable arrhythmia requiring treatment
- •History of symptomatic congestive heart failure (New York Heart Association Classes III or IV)
Arms & Interventions
pracinostat plus azacitadine
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
Intervention: pracinostat
pracinostat plus azacitadine
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
Intervention: Azacitidine
Placebo with Azacitadine
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
Intervention: Placebo
Placebo with Azacitadine
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
Intervention: Azacitidine
Outcomes
Primary Outcomes
Estimate efficacy
Time Frame: 6 months
Estimate the relative efficacy, measured by complete remission rate of treatment wiht pracinostat plus azacitidine versus placebo plus azacitidine
Secondary Outcomes
- Overall response rate(6 months)
- Hematologic Improvement(6 months)
- Duration of response(6 months)
- Progression free survival(12 months)
- Rate of leukemic transformation(6 - 24 months)
- Overall survival(6-24 months)
- AE profile(12 months)