Phase 2 Study of Pracinostat With Azacitidine in Patients With Previously Untreated Myelodysplastic Syndrome

Helsinn Healthcare

Status and phase: Completed; Phase 2

Conditions: Myelodysplastic Syndrome

Treatments: Drug: Azacitidine; Drug: Placebo; Drug: pracinostat

Study type: Interventional

Funder types: Industry

Identifiers

NCT01873703

MEI-003

Details and patient eligibility

About

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).

Enrollment: 102 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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102 participants in 2 patient groups, including a placebo group

pracinostat plus azacitadine

Experimental group

Description:

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

Treatment:

Drug: pracinostat

Drug: Azacitidine

Placebo with Azacitadine

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Drug: Azacitidine