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A Phase II Simon Two-Stage Study of the Addition of Pracinostat to a Hypomethylating Agent (HMA) in Patients With Myelodysplastic Syndrome (MDS) Who Have Failed to Respond or Maintain a Response to the HMA Alone
Description
Phase
Phase 2
Inclusion and Exclusion Criteria
- Inclusion Criteria:
- Voluntary written informed consent
- Histologically or cytologically documented diagnosis of MDS (any French-American-British classification [FAB] subtype)
- Bone marrow blasts >5% and <30% and a peripheral white blood cell (WBC) count of <20,000 /µL
- Bone marrow biopsy, aspirates, and peripheral blood smears within 28 days of first study treatment
- Group 1: Primary failures: Progression after their most recent HMA therapy according to IWG criteria after receiving single agent azacitidine and/or single agent decitabine, or has worsening cytopenias (increased transfusion requirement), increased BM blasts, progression to a higher FAB type, or develops additional clinically significant cytogenetic abnormalities; Secondary failures: Relapse after any initial CR, PR, HI, or development of clinically significant cytogenetic abnormalities at any time according to IWG criteria after receiving single agent azacitidine or decitabine Group 2: Failure to achieve a response (any CR, PR or HI) according to IWG criteria definition of stable disease after the most recent HMA therapy (at least 6 cycles of azacitidine or 4 cycles of decitabine)
- Must have demonstrated tolerability to single agent HMA
- Able to start combination therapy within 3 months of the last single agent HMA dose with no other therapy for disease under study received during this interval
- Not a candidate for hematopoietic stem cell transplant within 4 months of screening
- ECOG performance status of 0, 1, or 2
- Adequate organ function as evidenced by: - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x the upper limit of normal (ULN) - Total bilirubin ≤1.5 x ULN or total bilirubin of ≤2 mg/dL, whichever is higher - Serum creatinine <2 mg/dL, or creatinine clearance ≥60 mL/min - QTcF interval ≤470 msec
- Female or male patients ≥18 years-of-age
- Male patients with female partners are required to use two forms of acceptable contraception; Female patients of childbearing potential must have a negative pregnancy test ≤7 days before first study treatment.
- Willingness and ability to understand the nature of this trial and to comply Exclusion Criteria:
- Received any of the following within the specified time frame after the last single agent HMA dose until the first administration of study medication: - Any therapy for malignancy between the time of single agent HMA and first on-study treatment - Hydroxyurea within 48 hours prior to first study treatment - Hematopoietic growth factors: erythropoietin, granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), or thrombopoietin receptor agonists within 7 days (14 days for Aranesp) prior to first study treatment - Major surgery within 28 days of study day 1
- Patients who are candidates for aggressive chemotherapy (e.g. typical AML induction therapy)
- Cardiopulmonary function criteria: - Current unstable arrhythmia requiring treatment - History of symptomatic congestive heart failure (New York Heart Association Class III or IV) - History of myocardial infarction within 6 months of enrollment - Current unstable angina
- Concomitant treatment with agents that have activity against HDAC inhibitors is not permitted
- Clinical evidence of CNS involvement
- Patients with gastrointestinal (GI) tract disease, uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis)
- Active infection with human immunodeficiency virus or chronic hepatitis B or C
- Life-threatening illness unrelated to cancer or any serious medical or psychiatric illness that could 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 and other concurrent malignancies will be considered on a case by case basis
- Inability or unwillingness (including psychological, familial, sociological, or geographical conditions) to comply
Sites
-
California
- USC Norris Comprehensive Cancer Center, Los Angeles, California, 90033
- City of Hope, Duarte, California, 91010
- Sutter Medical Group, Sacramento, California, 95816
- Sutter Medical Group, Sacramento, California, 95816
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Colorado
- Colorado Blood Cancer Institute, Denver, Colorado, 80218
- Colorado Blood Cancer Institute, Denver, Colorado, 80218
-
Oklahoma
- University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, 73104
- University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, 73104
-
Texas
- Cancer Care Centers of South Texas, San Antonio, Texas, 78229
- Cancer Care Centers of South Texas, San Antonio, Texas, 78229
- Baylor University Medical Center, Dallas, Texas, 75246
- University of Texas Southwestern, Dallas, Texas, 75390
- University of Texas Southwestern, Dallas, Texas, 75390
- University of Texas Southwestern, Dallas, Texas, 75390
- MD Anderson Cancer Center, Houston, Texas, 77030
- MD Anderson Cancer Center, Houston, Texas, 77030
-
Kansas
- University of Kansas Cancer Center, Westwood, Kansas, 66205
-
Illinois
- Northwestern University, Chicago, Illinois, 60601
- Northwestern University, Chicago, Illinois, 60601
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Alabama
- Southern Cancer Center, Mobile, Alabama, 36608
- Southern Cancer Center, Mobile, Alabama, 36608
-
Tennessee
- Tennessee Oncology, Nashville, Tennessee, 37203
- Tennessee Oncology, Nashville, Tennessee, 37203
- Tennessee Oncology-Chattanooga, Chattanooga, Tennessee, 37404
- Tennessee Oncology-Chattanooga, Chattanooga, Tennessee, 37404
-
Kentucky
- University of Kentucky, Lexington, Kentucky, 40536
- University of Kentucky, Lexington, Kentucky, 40536
-
Ohio
- Oncology Hematology Care, Cincinati, Ohio, 45242
- Oncology Hematology Care, Cincinati, Ohio, 45242
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