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

Sponsor
Helsinn Healthcare SA (Industry)
Overall Status
Completed
CT.gov ID
NCT01873703
Collaborator
(none)
102
Enrollment
24
Locations
2
Arms
41
Duration (Months)
4.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
102 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, 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)
Study Start Date :
Jun 1, 2013
Actual Primary Completion Date :
Nov 1, 2015
Actual Study Completion Date :
Nov 1, 2016

Arms and Interventions

Arm Intervention/Treatment
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 Names:
  • 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 Names:
  • 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 Names:
  • Vidaza

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Estimate efficacy [6 months]

      Estimate the relative efficacy, measured by complete remission rate of treatment wiht pracinostat plus azacitidine versus placebo plus azacitidine

    Secondary Outcome Measures

    1. Overall response rate [6 months]

      Estimate the overall response rate [ORR = CR + complete remission + partial response (PR)]

    2. Hematologic Improvement [6 months]

      Estimate the overall hematologic improvement (HI) response rate by review of hematologic lab values each cycle including bone marrow blast counts, platelets and erythrocytes.

    3. Duration of response [6 months]

      Estimate the duration of response

    4. Progression free survival [12 months]

      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

    5. Rate of leukemic transformation [6 - 24 months]

      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

    6. Overall survival [6-24 months]

      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

    7. AE profile [12 months]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Locations

    Site City State Country Postal Code
    1 Southern Cancer Center Mobile Alabama United States 36608
    2 Scripps Cancer Center La Jolla California United States 92037
    3 Colorado Blood Cancer Institute Denver Colorado United States 80218
    4 Florida Cancer Specialists South Fort Myers Florida United States 33916
    5 Woodlands Medical Specialists Pensacola Florida United States 32503
    6 Florida Cancer Specialists North Saint Petersburg Florida United States 33705
    7 Florida Cancer Specialist and Research Institute Tallahassee Florida United States 32308
    8 H. Lee Moffitt Cancer Center Tampa Florida United States 33612
    9 Fort Wayne Medical Oncology and Hematology Fort Wayne Indiana United States 46804
    10 Indiana University Simon Cancer Ctr Indianapolis Indiana United States 46202
    11 Sidney Kimmel Comprehensive Cancer at Johns Hopkins Baltimore Maryland United States 21287
    12 Center for Cancer and Blood Disorders Bethesda Maryland United States 20817
    13 Henry Ford Hospital Detroit Michigan United States 48202
    14 Michigan State University Lansing Michigan United States 48910
    15 Nebraska Methodist Omaha Nebraska United States 68114
    16 Comprehensive Cancer Centers of Nevada Las Vegas Nevada United States 89148
    17 Weill Cornell Medical Center New York New York United States 10065
    18 Oncology Hematology Care Cincinnati Ohio United States 45242
    19 Cleveland Clinic Foundation Cleveland Ohio United States 44195
    20 Tennessee Oncology - Chattanooga Chattanooga Tennessee United States 37404
    21 Sarah Cannon Cancer Center, Tennessee Oncology Nashville Tennessee United States 37203
    22 MD Anderson Cancer Center Houston Texas United States 77030
    23 Cancer Care Centers of South Texas San Antonio Texas United States 78229
    24 Swedish Cancer Institute Seattle Washington United States 98104

    Sponsors and Collaborators

    • Helsinn Healthcare SA

    Investigators

    • Principal Investigator: Guillermo Garcia-Manero, MD, M.D. Anderson Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Helsinn Healthcare SA
    ClinicalTrials.gov Identifier:
    NCT01873703
    Other Study ID Numbers:
    • MEI-003
    First Posted:
    Jun 10, 2013
    Last Update Posted:
    Sep 13, 2018
    Last Verified:
    Sep 1, 2018
    Keywords provided by Helsinn Healthcare SA
    MDS
    High risk myelodysplastic syndrome
    Intermediate-2 Myelodysplastic syndrome
    Untreated
    Additional relevant MeSH terms:
    Preleukemia
    Myelodysplastic Syndromes
    Syndrome
    Azacitidine

    Study Results

    No Results Posted as of Sep 13, 2018