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Trial record 1 of 1 for:    MEI-011
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A Safety and Efficacy Study of Pracinostat and Azacitidine in Patients With High Risk Myelodysplastic Syndromes

This study is currently recruiting participants.
Verified August 2017 by Helsinn Healthcare SA
Sponsor:
ClinicalTrials.gov Identifier:
NCT03151304
First Posted: May 12, 2017
Last Update Posted: November 15, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Helsinn Healthcare SA
  Purpose

This is a Phase 2, two-stage study of the safety and efficacy of pracinostat in combination with azacitidine in patients with IPSS-R high and very high risk MDS who are previously untreated with HMAs. Enrollment in this study will be limited to high/very high risk MDS because this group represents the highest unmet need, with median survival of less than 18 months.

Stage 1 will be conducted as an open-label single arm in up to 40 subjects to assess if this regimen with a lower pracinostat dose results in a discontinuation rate that meets a predefined threshold and in efficacy that justifies expansion of enrollment into Stage 2.

A discontinuation rate of approximately ≤10% in Stage 1, a rate comparable to that observed with azacitidine alone in study MEI-003, is considered desirable and supports expansion into Stage 2.

Stage 2 will be conducted as a randomized, double-blind, placebo-controlled, two-arm design to confirm that the discontinuation rate observed in an open-label design can be reproduced in a placebo controlled design, and to provide unbiased information on efficacy and safety. Subjects will be randomized in a 1:1 ratio to one of the 2 treatment arms (Arm A, pracinostat + azacitidine and Arm B, placebo + azacitidine). Study drugs should be continued until disease progression or intolerable toxicity. It is important to note that the median time to achieving a response with azacitidine alone is 4 to 5 months. Furthermore, the median time to achieving a CR in study MEI-003 was 4 cycles. Therefore, early (<6 months) discontinuation of trial therapy for 'no response' should be avoided. The Medical Monitor should be contacted prior to discontinuing a subject from the study to discuss the rationale for discontinuation.


Condition Intervention Phase
Myelodysplastic Syndromes Drug: Pracinostat Drug: Azacitidine Drug: Placebos Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
Two-Stage, Open-Label Followed by Placebo-Controlled Study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Two-Stage, Open-Label Followed by Placebo-Controlled Phase 2 Study of Pracinostat and Azacitidine in Patients With IPSS-R High and Very High Risk Myelodysplastic Syndromes Previously Untreated With Hypomethylating Agents

Resource links provided by NLM:


Further study details as provided by Helsinn Healthcare SA:

Primary Outcome Measures:
  • overall response rate (ORR), [ Time Frame: 36 months ]
    Define the rate of overall response rate (ORR), defined as complete remission (CR), partial remission (PR) and marrow CR, of pracinostat plus azacitidine in high/very high risk MDS


Secondary Outcome Measures:
  • Complete response (CR) rate [ Time Frame: 36 months ]
    the proportion of subjects with confirmed CR (i.e., 2 CRs at least 28 days apart) according to the IWG criteria

  • Overall hematologic improvement (HI) response rate [ Time Frame: 36 months ]
    proportion of subjects who demonstrate major hematologic improvement as defined by the IWG criteria

  • Clinical benefit rate [ Time Frame: 36 months ]
    defined as rate of CR + PR + HI + Marrow CR

  • Rate of cytogenetic complete response/remission [ Time Frame: 36 months ]
    proportion of subjects with confirmed CR by cytogenetic assessment

  • Duration of response (DoR) [ Time Frame: 36 months ]
    the time from the initial determination of response to the time of disease progression or death on study, whichever occurs first

  • Rate of leukemic transformation [ Time Frame: 6, 12, 18 and 24 months ]
    transformation at landmark time points of 6 months, 12 months, 18 months, and 24 months

  • Duration of event-free survival (EFS) [ Time Frame: 36 months ]
    time from the first day of study drug administration (Day 1) to failure or death from any cause

  • Duration of progression-free survival (PFS) [ Time Frame: 36 months ]
    time from the first day of study drug administration (Day 1) to disease recurrence or progression as defined by the IWG criteria, or death on study

  • Duration of overall survival (OS) [ Time Frame: form day 1 to death on study, assessed up to 36 months ]
    time from the first day of study drug administration (Day 1) to death on study


Estimated Enrollment: 120
Actual Study Start Date: June 1, 2017
Estimated Study Completion Date: June 2020
Estimated Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Stage 1 open-label pracinostat plus azacitidine

open-label single arm pracinostat plus azacitidine. Pracinostat: 45 mg administered orally 3 days each week for 3 consecutive weeks, followed by 1 week of rest, in 28-day cycles.

In later cycles (i.e., after Cycle 4), pracinostat dose reduction to 45 mg orally 3 days each week × 2 weeks (instead of 3 weeks) or dose interruption is allowed to manage toxicity such as fatigue, gastrointestinal toxicity, or myelosuppression.

Azacitine: 75 mg/m2 for 7 days of each 28-day cycle. Administration will occur by subcutaneous (SC) injection, or IV infusion if SC injections are not tolerated, on one of two schedules:

  • Schedule 1 - daily therapy on Days 1 through 7
  • Schedule 2 - 5-2-2 schedule in which subjects receive azacitidine for 5 consecutive days (Days 1 through 5) with rest on Days 6 and 7, and resume azacitidine dosing the first two days of the next week (Days 8 and 9) of each 28-day cycle
Drug: Pracinostat
45 mg capsule
Other Name: SB939
Drug: Azacitidine
SC or IV injection
Experimental: Stage 2 pracinostat plus azacitidine

Pracinostat: 45 mg administered orally 3 days each week for 3 consecutive weeks, followed by 1 week of rest, in 28-day cycles.

In later cycles (i.e., after Cycle 4), pracinostat dose reduction to 45 mg orally 3 days each week × 2 weeks (instead of 3 weeks) or dose interruption is allowed to manage toxicity such as fatigue, gastrointestinal toxicity, or myelosuppression.

Azacitine: 75 mg/m2 for 7 days of each 28-day cycle. Administration will occur by subcutaneous (SC) injection, or IV infusion if SC injections are not tolerated, on one of two schedules:

  • Schedule 1 - daily therapy on Days 1 through 7
  • Schedule 2 - 5-2-2 schedule in which subjects receive azacitidine for 5 consecutive days (Days 1 through 5) with rest on Days 6 and 7, and resume azacitidine dosing the first two days of the next week (Days 8 and 9) of each 28-day cycle
Drug: Pracinostat
45 mg capsule
Other Name: SB939
Drug: Azacitidine
SC or IV injection
Placebo Comparator: Stage 2 placebo plus azacitidine

Placebo: orally 3 days each week for 3 consecutive weeks, followed by 1 week of rest, in 28-day cycles.

Azacitine: 75 mg/m2 for 7 days of each 28-day cycle. Administration will occur by subcutaneous (SC) injection, or IV infusion if SC injections are not tolerated, on one of two schedules:

  • Schedule 1 - daily therapy on Days 1 through 7
  • Schedule 2 - 5-2-2 schedule in which subjects receive azacitidine for 5 consecutive days (Days 1 through 5) with rest on Days 6 and 7, and resume azacitidine dosing the first two days of the next week (Days 8 and 9) of each 28-day cycle
Drug: Azacitidine
SC or IV injection
Drug: Placebos
oral capsules

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Female or male subjects ≥18 years-of-age.
  2. Histologically or cytologically documented diagnosis of MDS according to the World Health Organization (WHO) classification (Vardiman 2009, Arber 2016) with >5% and <20% bone marrow blasts by morphology and a peripheral white blood cell (WBC) count of <20,000/μL

    • If WBC ≥20,000/μL, cytoreduction with hydroxyurea is permitted prior to enrollment.
  3. Classified as high or very high risk according to the Revised International Prognostic Scoring System (IPSS-R) risk category.
  4. Bone marrow biopsy (BMBx) within 28 days prior to first study treatment.
  5. Clinical indication for treatment with azacitidine.
  6. Previously untreated with HMAs (prior therapy with transfusions, hematopoietic growth factors, or immunosuppressive therapy is allowed).
  7. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
  8. Adequate organ function as evidenced by:

    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × the upper limit of normal (ULN).
    • Total bilirubin ≤1.5 × ULN or total bilirubin of ≤2 mg/dL, whichever is higher.
    • Serum creatinine <2 mg/dL, or creatinine clearance ≤1.5 × ULN.
    • QTcF interval ≤450 msec using the mean of triplicate electrocardiograms (ECGs).
  9. Female subjects of childbearing potential and male subjects with female partners of childbearing potential are required to use two forms of acceptable contraception, including one barrier method, during their participation in the study and for 30 days following last dose. Female subjects of childbearing potential must not be breastfeeding, or planning to breastfeed, and must have a negative pregnancy test ≤7 days before first study drug administration.

    Male subjects must also refrain from donating sperm during their participation in the study.

  10. Voluntary written informed consent before performance of any study-related procedure not part of normal medical care.
  11. Have the willingness and ability to understand the nature of this study and to comply with the study and follow-up procedures.

Exclusion Criteria:

  1. Bone marrow blasts ≥20%, indicating a diagnosis of acute myeloid leukemia (AML).
  2. 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 enrollment, whichever is longer.
    • Hydroxyurea within 48 hours prior to first day of 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 28 days prior to first study treatment.
  3. Subjects that have not recovered from side effects of previous therapy.
  4. Cardiopulmonary function criteria:

    • Current unstable arrhythmia requiring treatment.
    • History of symptomatic congestive heart failure (New York Heart Association [NYHA] Class III or IV).
    • History of myocardial infarction within 6 months of enrollment.
    • Current unstable angina.
  5. Prior treatment for MDS with the histone deacetylase (HDAC) inhibitors Zolinza (vorinostat), Belenodaq (belinostat), Farydak (panobinostat), Istodax (romidepsin/depsipetide), or investigational agent with significant action as an HDAC inhibitor.
  6. Clinical evidence of central nervous system involvement.
  7. Subjects with gastrointestinal (GI) tract disease causing the inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis).
  8. Uncontrolled infection with human immunodeficiency virus (HIV) or chronic hepatitis B or C.
  9. 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.
  10. Presence of a malignant disease within the last 12 months, with the exception of adequately treated in-situ carcinomas, basal or squamous cell carcinoma, non-melanomatous skin cancer, or malignancies treated with curative intent and no evidence of active disease in prior 12 months and felt to be low risk for recurrence.
  11. An unwillingness or inability (including psychological, familial, sociological, or geographical conditions) to comply with trial and/or follow-up procedures as outlined in the protocol
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03151304


Contacts
Contact: Christy Romanowski 949-229-6304 cromanowski@clinipace.com
Contact: Amanda Hughes 858-369-7119 ahughes@meipharma.com

Locations
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Scripps Cancer Center-Mercy Recruiting
San Diego, California, United States, 92103
United States, Louisiana
Pontchartrain cancer Center Recruiting
Covington, Louisiana, United States, 70433
United States, Maryland
RCCA MD LLC (The Center for Cancer and Blood Disorders) Recruiting
Bethesda, Maryland, United States, 20817
United States, Michigan
Michigan Center of Medical Research Recruiting
Farmington Hills, Michigan, United States, 48334
Michigan State University, Breslin Cancer Center Recruiting
Lansing, Michigan, United States, 48910
United States, Missouri
Mercy Medical Research Institute Recruiting
Springfield, Missouri, United States, 65807
United States, New York
Stony Brook University Recruiting
Stony Brook, New York, United States, 11794
United States, Ohio
Oncology Hematology Care Recruiting
Cincinnati, Ohio, United States, 45242
United States, Oklahoma
Cancer Centers of Southwest Oklahoma Recruiting
Lawton, Oklahoma, United States, 73501
Oklahoma Cancer Specialists and Research Institute Recruiting
Tulsa, Oklahoma, United States, 74146
United States, Texas
UT Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
United States, Virginia
UVA Health System Division of Hematology & Oncology Recruiting
Charlottesville, Virginia, United States, 22908
United States, Washington
Swedish Cancer Institute Recruiting
Seattle, Washington, United States, 98104
United States, Wisconsin
Universityof Wisconsin Clinical Science Center Recruiting
Madison, Wisconsin, United States, 53792
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Helsinn Healthcare SA
Investigators
Study Director: Richard Ghalie, MD MEI Pharma
Study Chair: Guillermo Garcia-Manero, MD MD Anderson
  More Information

Responsible Party: Helsinn Healthcare SA
ClinicalTrials.gov Identifier: NCT03151304     History of Changes
Other Study ID Numbers: MEI-011
First Submitted: May 5, 2017
First Posted: May 12, 2017
Last Update Posted: November 15, 2017
Last Verified: August 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Helsinn Healthcare SA:
MDS

Additional relevant MeSH terms:
Syndrome
Myelodysplastic Syndromes
Preleukemia
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors