Clinical trial NCT01873703: Phase 2 Study of Pracinostat With Azacitidine in Patients With Previously Untreated Myelodysplastic Syndrome
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myelodysplastic Syndrome
Keywords: MDS
High risk myelodysplastic syndrome
Intermediate-2 Myelodysplastic syndrome
Untreated
Lead sponsor: Helsinn Healthcare SA
Sponsor class: INDUSTRY
First posted: 2013-06-10
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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:

  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

Primary outcomes:
measure: Estimate efficacy
timeFrame: 6 months
Secondary outcomes:
measure: Overall response rate
timeFrame: 6 months
measure: Hematologic Improvement
timeFrame: 6 months
measure: Duration of response
timeFrame: 6 months
measure: Progression free survival
timeFrame: 12 months
measure: Rate of leukemic transformation
timeFrame: 6 - 24 months
measure: Overall survival
timeFrame: 6-24 months
measure: AE profile
timeFrame: 12 months
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Southern Cancer Center
state: Alabama
city: La Jolla
country: United States
facility: Scripps Cancer Center
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Fort Myers
country: United States
facility: Florida Cancer Specialists South
state: Florida
city: Pensacola
country: United States
facility: Woodlands Medical Specialists
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists North
state: Florida
city: Tallahassee
country: United States
facility: Florida Cancer Specialist and Research Institute
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Simon Cancer Ctr
state: Indiana
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer at Johns Hopkins
state: Maryland
city: Bethesda
country: United States
facility: Center for Cancer and Blood Disorders
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Lansing
country: United States
facility: Michigan State University
state: Michigan
city: Omaha
country: United States
facility: Nebraska Methodist
state: Nebraska
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: New York
country: United States
facility: Weill Cornell Medical Center
state: New York
city: Cincinnati
country: United States
facility: Oncology Hematology Care
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Chattanooga
country: United States
facility: Tennessee Oncology - Chattanooga
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Cancer Center, Tennessee Oncology
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Centers of South Texas
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Guillermo Garcia-Manero, MD
role: PRINCIPAL_INVESTIGATOR
References: