Trial record 1 of 1 for:    MEI-003
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Phase 2 Study of Pracinostat With Azacitidine in Patients With Previously Untreated Myelodysplastic Syndrome

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by MEI Pharma, Inc.
Sponsor:
Information provided by (Responsible Party):
MEI Pharma, Inc.
ClinicalTrials.gov Identifier:
NCT01873703
First received: May 22, 2013
Last updated: June 11, 2014
Last verified: June 2014
  Purpose

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).


Condition Intervention Phase
Myelodysplastic Syndrome
Drug: pracinostat
Drug: Placebo
Drug: Azacitidine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by MEI Pharma, Inc.:

Primary Outcome Measures:
  • Estimate efficacy [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Estimate the relative efficacy, measured by complete remission rate of treatment wiht pracinostat plus azacitidine versus placebo plus azacitidine


Secondary Outcome Measures:
  • Overall response rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Estimate the overall response rate [ORR = CR + complete remission + partial response (PR)]

  • Hematologic Improvement [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Estimate the overall hematologic improvement (HI) response rate by review of hematologic lab values each cycle including bone marrow blast counts, platelets and erythrocytes.

  • Duration of response [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Estimate the duration of response

  • Progression free survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Estimate the progression-free survival (PFS) duration of pracinostat plus azacitidine and the relative benefit of that combination versus placebo plus azacitidine as assessed by the PFS hazard ratio

  • Rate of leukemic transformation [ Time Frame: 6 - 24 months ] [ Designated as safety issue: No ]
    Estimate the rate of leukemic transformation at landmark time points (6 months, 12 months, 18 months, and 24 months) using clinical review of hematologic lab counts each cycle

  • Overall survival [ Time Frame: 6-24 months ] [ Designated as safety issue: No ]
    Estimate the overall survival (OS) duration of pracinostat plus azacitidine and the relative benefit of that combination versus placebo plus azacitidine as assessed by the OS hazard ratio

  • AE profile [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Assess the adverse event (AE) profile of pracinostat and placebo when combined with azacitidine by clinical review of safety events by grade, relationship and event outcomes.


Estimated Enrollment: 100
Study Start Date: June 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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

Drug: pracinostat
Histone deacetylase inhibitor (HDACi)
Other Name: SB939
Drug: Azacitidine
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
Other Name: Vidaza
Placebo Comparator: 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

Drug: Placebo
Placebo
Drug: Azacitidine
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
Other Name: Vidaza

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01873703

  Show 24 Study Locations
Sponsors and Collaborators
MEI Pharma, Inc.
Investigators
Principal Investigator: Guillermo Garcia-Manero, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: MEI Pharma, Inc.
ClinicalTrials.gov Identifier: NCT01873703     History of Changes
Other Study ID Numbers: MEI-003
Study First Received: May 22, 2013
Last Updated: June 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by MEI Pharma, Inc.:
MDS
High risk myelodysplastic syndrome
Intermediate-2 Myelodysplastic syndrome
Untreated

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Azacitidine
Histone Deacetylase Inhibitors
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 22, 2014