Azacitidine With or Without Entinostat in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia
Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Eligibility Criteria
Inclusion Criteria: The following diagnoses will be eligible for this study: Myelodysplastic syndromes: the diagnosis of MDS must be confirmed by a bone marrow aspirate and/or biopsy within two weeks prior to registration; NOTE: blast count must be < 20%; patients with any International Prognostic Score (IPSS) are eligible; patients with low or intermediate (INT)-1 IPSS must have a platelet count < 50,000/mm^3 and/or absolute neutrophil count (ANC) < 500/mm^3 within seven days prior to registration Chronic myelomonocytic leukemia (dysplastic subtype): the diagnosis of CMMoL must be confirmed by a bone marrow aspirate and/or biopsy within two weeks prior to registration; patients with CMMoL must have a WBC < 12,000/mm^3, documented within 4 weeks prior to study entry (two sets of counts that are 2 weeks apart will be taken) Acute myeloid leukemia with multilineage dysplasia: the diagnosis of AML-TLD must be confirmed by a bone marrow aspirate and/or biopsy within two weeks prior to registration; NOTE: there must be evidence of >= 20% blasts on the review of the bone marrow aspirate and/or biopsy; AML-TLD will be interpreted to include patients formerly diagnosed by French-American-British (FAB) criteria as refractory anemia with excess blasts in transformation (RAEB-t), as well as patients with no history of antecedent hematologic disorder who have AML which meets criteria for AML-TLD by World Health Organization (WHO) criteria; patients with AML-TLD must have a white blood cell (WBC) =< 30,000/mm^3 documented within 4 weeks prior to study entry (two sets of counts that are 2 weeks apart will be taken); patients whose WBC has doubled within this period of time and is greater than 20,000/mm^3 at the time of screening will not be eligible Women must not be pregnant or breast-feeding; all females of childbearing potential must have a blood test or urine study within two weeks prior to registration to rule out pregnancy Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception Patient must have Eastern Cooperative Oncology Group (ECOG) performance status between 0-2 Patient must have no prior treatment with azacitidine, decitabine or entinostat Patients must not have active infections at the time of registration Serum creatinine < 2.0 mg/dL; test must be done within seven days prior to registration Total serum bilirubin within institutional limits unless due to intra- or extramedullary hemolysis or Gilbert's syndrome; test must be done within seven days prior to registration Aspartate transaminase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine transaminase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (ULN); tests must be done within seven days prior to registration Patients must not have received any AML induction chemotherapy or stem cell transplantation; any other treatment for their disease, including hematopoietic growth factors may not be given, within three weeks prior to registration, and should have recovered from all toxicities of prior therapy (to grade 0 or 1) Patients must have no clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS leukemia Patients must have no serious or uncontrolled medical conditions Patients who have therapy-induced MDS, CMMoL (dysplastic) and AML-TLD are eligible and will be treated as separate cohorts from the patients with de novo MDS, CMMoL (dysplastic) and AML-TLD Patients should have a life expectancy of at least six months Patients must not have advanced malignant hepatic tumors Patients must not have a known hypersensitivity to azacitidine or mannitol Southwest Oncology Group (SWOG) ONLY: all SWOG patients must be registered on SWOG-9007 ("Cytogenetic Studies in Leukemia Patients"); collection of the pretreatment bone marrow specimen (or of peripheral blood if the marrow is not aspirable) must be completed within 28 days before registration; the pretreatment specimen must be submitted to a SWOG-approved cytogenetics laboratory as described in protocol SWOG-9007; note that submission of bone marrow cytogenetic studies are required to calculate the IPSS score (stratification issue); in addition, cytogenetic response will be measured at follow-up requiring a second cytogenetic study at the end of protocol treatment; NOTE: In addition to SWOG-9007, SWOG patients must be offered participation in S9910, the leukemia centralized reference laboratories and tissue repositories ancillary study; If consent is given, collection of pretreatment blood and/or marrow specimens must be completed within 14 days prior to registration. If the patient consents to participate in S9910, pretreatment specimens of marrow and/or peripheral blood must be submitted to the Southwest Oncology Group Myeloid Repository at the University of New Mexico for cellular and molecular studies; S9910 also requests submission of remission and relapse specimens
Sites / Locations
- Mayo Clinic in Arizona
- Providence Saint Joseph Medical Center/Disney Family Cancer Center
- Los Angeles Oncology Institute
- Stanford Cancer Institute
- Sutter Roseville Medical Center
- Sutter General Hospital
- The Medical Center of Aurora
- Boulder Community Hospital
- Penrose-Saint Francis Healthcare
- Porter Adventist Hospital
- Presbyterian - Saint Lukes Medical Center - Health One
- SCL Health Saint Joseph Hospital
- Rose Medical Center
- Colorado Cancer Research Program NCORP
- Swedish Medical Center
- Poudre Valley Hospital
- Front Range Cancer Specialists
- Saint Mary's Hospital and Regional Medical Center
- North Colorado Medical Center
- Saint Anthony Hospital
- Sky Ridge Medical Center
- Longmont United Hospital
- McKee Medical Center
- Saint Mary Corwin Medical Center
- North Suburban Medical Center
- SCL Health Lutheran Medical Center
- Beebe Medical Center
- Christiana Care Health System-Christiana Hospital
- Sibley Memorial Hospital
- Emory University/Winship Cancer Institute
- Rush - Copley Medical Center
- MacNeal Hospital and Cancer Center
- Saint Joseph Medical Center
- Illinois CancerCare-Bloomington
- Graham Hospital Association
- Illinois CancerCare-Canton
- Illinois CancerCare-Carthage
- Memorial Hospital
- Hematology and Oncology Associates
- Northwestern University
- Jesse Brown Veterans Affairs Medical Center
- John H Stroger Jr Hospital of Cook County
- University of Illinois
- Mercy Hospital and Medical Center
- University of Chicago Comprehensive Cancer Center
- Weiss Memorial Hospital
- Presence Saint Joseph Hospital-Chicago
- Decatur Memorial Hospital
- Heartland Cancer Research NCORP
- Eureka Hospital
- Illinois CancerCare-Eureka
- NorthShore University HealthSystem-Evanston Hospital
- Galesburg Cottage Hospital
- Illinois CancerCare-Galesburg
- Illinois CancerCare-Havana
- Mason District Hospital
- Hopedale Medical Complex - Hospital
- Midwest Center for Hematology Oncology
- Joliet Oncology-Hematology Associates Limited
- Illinois CancerCare-Kewanee Clinic
- NorthShore Hematology Oncology-Libertyville
- Illinois CancerCare-Macomb
- Mcdonough District Hospital
- Loyola University Medical Center
- Holy Family Medical Center
- Illinois CancerCare-Monmouth
- DuPage Medical Group-Ogden
- Illinois Cancer Specialists-Niles
- Bromenn Regional Medical Center
- Community Cancer Center Foundation
- Illinois CancerCare-Community Cancer Center
- Illinois CancerCare-Ottawa Clinic
- Ottawa Regional Hospital and Healthcare Center
- Illinois CancerCare-Pekin
- OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
- Pekin Hospital
- Methodist Medical Center of Illinois
- Proctor Hospital
- Illinois CancerCare-Peoria
- OSF Saint Francis Medical Center
- Illinois CancerCare-Peru
- Illinois Valley Hospital
- Illinois CancerCare-Princeton
- Perry Memorial Hospital
- Swedish American Hospital
- SwedishAmerican Regional Cancer Center/ACT
- Edward H Kaplan MD and Associates
- Hematology Oncology Associates of Illinois - Skokie
- Illinois CancerCare-Spring Valley
- Saint Margaret's Hospital
- Memorial Medical Center
- Carle Clinic-Urbana Main
- Fort Wayne Medical Oncology and Hematology Inc-Parkview
- Franciscan Saint Anthony Health-Michigan City
- McFarland Clinic PC-William R Bliss Cancer Center
- Medical Oncology and Hematology Associates-West Des Moines
- Mercy Capitol
- Iowa Methodist Medical Center
- Iowa-Wide Oncology Research Coalition NCORP
- Medical Oncology and Hematology Associates-Des Moines
- Medical Oncology and Hematology Associates-Laurel
- Mercy Medical Center - Des Moines
- Iowa Lutheran Hospital
- University of Iowa/Holden Comprehensive Cancer Center
- Siouxland Regional Cancer Center
- Mercy Medical Center-Sioux City
- Saint Luke's Regional Medical Center
- Hospital District Sixth of Harper County
- Cancer Center of Kansas - Chanute
- Cancer Center of Kansas - Dodge City
- Cancer Center of Kansas - El Dorado
- Cancer Center of Kansas - Fort Scott
- Cancer Center of Kansas-Independence
- Providence Medical Center
- Cancer Center of Kansas-Kingman
- Lawrence Memorial Hospital
- Cancer Center of Kansas-Liberal
- Cancer Center of Kansas - Newton
- Menorah Medical Center
- Radiation Oncology Practice Corporation Southwest
- Saint Luke's South Hospital
- Cancer Center of Kansas - Parsons
- Kansas City NCI Community Oncology Research Program
- Cancer Center of Kansas - Pratt
- Cancer Center of Kansas - Salina
- Salina Regional Health Center
- Shawnee Mission Medical Center-KCCC
- Saint Francis Hospital and Medical Center - Topeka
- Cancer Center of Kansas - Wellington
- Associates In Womens Health
- Cancer Center of Kansas-Wichita Medical Arts Tower
- Cancer Center of Kansas - Wichita
- Via Christi Regional Medical Center
- Wichita NCI Community Oncology Research Program
- Cancer Center of Kansas - Winfield
- Eastern Maine Medical Center
- University of Maryland/Greenebaum Cancer Center
- Johns Hopkins University/Sidney Kimmel Cancer Center
- Union Hospital of Cecil County
- Boston Medical Center
- Henry Ford Hospital
- Sanford Clinic North-Bemidgi
- Lake Region Healthcare Corporation-Cancer Care
- University of Minnesota/Masonic Cancer Center
- Mayo Clinic
- Southeast Missouri Hospital
- Veterans Administration
- University of Missouri - Ellis Fischel
- Centerpoint Medical Center LLC
- Truman Medical Center
- Saint Luke's Cancer Institute
- Saint Luke's Hospital of Kansas City
- Radiation Oncology Practice Corporation South
- Saint Joseph Health Center
- North Kansas City Hospital
- Heartland Hematology and Oncology Associates Incorporated
- Research Medical Center
- Radiation Oncology Practice Corporation - North
- Saint Luke's East - Lee's Summit
- Liberty Hospital
- Liberty Radiation Oncology Center
- Heartland Regional Medical Center
- Saint Joseph Oncology Inc
- Saint Louis University Hospital
- Billings Clinic Cancer Center
- Montana Cancer Consortium NCORP
- Northern Rockies Radiation Oncology Center
- Saint Vincent Healthcare
- Frontier Cancer Center and Blood Institute-Billings
- Bozeman Deaconess Cancer Center
- Bozeman Deaconess Hospital
- Saint James Community Hospital and Cancer Treatment Center
- Benefis Healthcare- Sletten Cancer Institute
- Berdeaux, Donald MD (UIA Investigator)
- Big Sky Oncology
- Great Falls Clinic
- Northern Montana Hospital
- Saint Peter's Community Hospital
- Glacier Oncology PLLC
- Kalispell Medical Oncology
- Kalispell Regional Medical Center
- Montana Cancer Specialists
- Saint Patrick Hospital - Community Hospital
- Community Medical Hospital
- Guardian Oncology and Center for Wellness
- Ocean Medical Center
- Cooper Hospital University Medical Center
- Presbyterian Kaseman Hospital
- Montefiore Medical Center-Weiler Hospital
- Montefiore Medical Center - Moses Campus
- Roswell Park Cancer Institute
- Adirondack Cancer Center
- Northwell Health NCORP
- North Shore University Hospital
- Orange Regional Medical Center
- Long Island Jewish Medical Center
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
- Mount Sinai Medical Center
- Carolinas Medical Center/Levine Cancer Institute
- East Carolina University
- Kinston Medical Specialists PA
- Wake Forest University Health Sciences
- Sanford Clinic North-Fargo
- Sanford Medical Center-Fargo
- Akron General Medical Center
- Case Western Reserve University
- Bryn Mawr Hospital
- Geisinger Medical Center
- Geisinger Medical Center-Cancer Center Hazleton
- Paoli Memorial Hospital
- Fox Chase Cancer Center
- University of Pittsburgh Cancer Institute (UPCI)
- Mercy Hospital
- Scranton Hematology Oncology
- Geisinger Medical Group
- Geisinger Wyoming Valley/Henry Cancer Center
- Lankenau Medical Center
- Main Line Health NCORP
- WellSpan Health-York Hospital
- Sanford Cancer Center-Oncology Clinic
- Medical X-Ray Center
- Sanford USD Medical Center - Sioux Falls
- Jackson-Madison County General Hospital
- University of Tennessee - Knoxville
- Zale Lipshy University Hospital
- Clements University Hospital
- UT Southwestern/Simmons Cancer Center-Dallas
- Scott and White Memorial Hospital
- Cottonwood Hospital Medical Center
- Danville Regional Medical Center
- University of Wisconsin Hospital and Clinics
- Medical Consultants Limited
- Rocky Mountain Oncology
- Welch Cancer Center
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Arm A (azacitidine)
Arm B (azacitidine, entinostat)
Patients receive azacitidine SC QD on days 1-10. Treatment repeats every 28 days for 6-24 courses in the absence of disease progression or unacceptable toxicity.
Patients receive azacitidine as in Arm A and entinostat PO on days 3 and 10. Treatment repeats every 28 days for 6-24 courses in the absence of disease progression or unacceptable toxicity.