Azacitidine With or Without Lenalidomide or Vorinostat in Treating Patients With Higher-Risk Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia

Myelodysplastic Syndrome Clinical Trial

Official title:

A Randomized Phase II/III Study of Azacitidine in Combination With Lenalidomide (NSC-703813) vs. Azacitidine Alone vs. Azacitidine in Combination With Vorinostat (NSC-701852) for Higher-Risk Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01522976
• Other study ID #: NCI-2012-00242
• Secondary ID: NCI-2012-00242CD
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 1, 2012
• Est. completion date: March 7, 2025

Study information

• Verified date: March 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase II/III trial studies how well azacitidine works with or without lenalidomide or vorinostat in treating patients with higher-risk myelodysplastic syndromes or chronic myelomonocytic leukemia. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, stopping them from dividing, or by stopping them from spreading. Lenalidomide may stop the growth of cancer cells by stopping blood flow to the cancer. Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether azacitidine is more effective with or without lenalidomide or vorinostat in treating myelodysplastic syndromes or chronic myelomonocytic leukemia.

Description:

PRIMARY OBJECTIVES:

I. To select based on response rate (complete remission, partial remission, or hematologic improvement) either the combination of lenalidomide and azacitidine or the combination of vorinostat and azacitidine for further testing against single-agent azacitidine among patients with higher-risk myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML). (Phase II) II. To compare overall survival between the combination arm selected in the Phase II portion of the trial to single-agent azacitidine among patients with higher-risk myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML). (Phase III)

SECONDARY OBJECTIVES:

I. To estimate relapse-free survival, overall survival and cytogenetic response rate of patients treated on each regimen.

II. To estimate the frequency and severity of toxicities of the three regimens in this patient population.

III. To investigate in a preliminary manner the frequency of subgroups from prestudy cytogenetic studies and correlate these subgroups with clinical outcomes in this patient population.

IV. To collect specimens for banking for use in future research studies.

TERTIARY OBJECTIVES:

I. To evaluate the prevalence of a pre-specified list of molecular lesions (48 total lesions).

II. To assess associations of these lesions with outcomes (response, event-free survival, relapse-free survival, and overall survival).

III. To develop a deoxyribonucleic acid (DNA) methylation biomarker predictive of response to DMTi treatment in MDS.

IV. To harness gene expression profiles as clinical biomarkers of primary resistance to DMTi in MDS.

OUTLINE: Patients are randomized to 1 of 3 treatment arms. In Phase III, patients are randomized to 1 of 2 treatment arms (the combination arm selected in Phase II or the single-agent azacitidine arm).

ARM I: Patients receive azacitidine subcutaneously (SC) or intravenously (IV) on days 1-7 or days 1-5 and 8-9, and lenalidomide orally (PO) once daily (QD) on days 1-21.

ARM II: Patients receive azacitidine as in Arm I.

ARM III: Patients receive azacitidine as in Arm I and vorinostat PO twice daily (BID) on days 3-9.

In all arms, treatment repeats every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 5 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 282
• Est. completion date: March 7, 2025
• Est. primary completion date: June 1, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have morphologically confirmed diagnosis of myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) based on one of the following:

• French-American-British (FAB) classifications:

• Refractory anemia with excess blasts (RAEB - defined as having 5-20% myeloblasts in the bone marrow)

• Chronic myelomonocytic leukemia (CMML) with 10-19% myeloblasts in the bone marrow and/or 5-19% blasts in the blood

• World Health Organization (WHO) classifications:

• Refractory anemia with excess blasts-1 (RAEB-1 - defined as having 5-9% myeloblasts in the bone marrow)

• Refractory anemia with excess blasts-2 (RAEB-2 - defined as having 10-19% myeloblasts in the bone marrow and/or 5-19% blasts in the blood)

• Chronic myelomonocytic leukemia-1 (CMML-1 - defined as having < 10% myeloblasts in the bone marrow and/or < 5% blasts in the blood)

• Chronic myelomonocytic leukemia-2 (CMML-2 - defined as having 10-19% myeloblasts in the bone marrow and/or 5-19% blasts in the blood) OR

• International prognostic score (IPSS) of intermediate 2 (1.5-2.0 points) or high (>= 2.5 points); a score of intermediate 1 (0.5-1.0 points) is only allowable in the setting of >= 5% myeloblasts

• NOTE: Patients with acute myeloid leukemia (AML) are not eligible

• Procedures to obtain specimens for establishing baseline disease must be done within 30 days prior to registration

• Patients must not have received lenalidomide, azacitidine, vorinostat, or decitabine as treatment previously; any hematopoietic growth factors must be stopped for at least 14 days prior to registration; patients may have received low-dose cytarabine for MDS treatment previously, but they must have discontinued its use for at least 28 days prior to registration; patients may have received prior hydroxyurea per CMML treatment previously, but they must have discontinued its use for at least 7 days prior to registration; these patients will not be eligible if white blood cell (WBC) > 30,000/mm^3

• Patients must not have received radiation therapy, chemotherapy, or cytotoxic therapy to treat conditions other than MDS within 12 months prior to registration

• Patients must not have undergone prior allogeneic stem cell or bone marrow transplantation at any time; patients that have undergone an autologous stem cell transplant are eligible

• Patients must not have used or be using histone deacetylase (HDAC) inhibitor agents for anticancer treatment

• Patients may not have received agents such as valproic acid for epilepsy within 30 days prior to registration

• Patients must have Zubrod performance status of 0-2

• Patients must not have any pre-existing neurotoxicity/neuropathy of >= grade 2 according to the National Cancer Institute (NCI) Common Toxicity Criteria version 4.0, or prior >= grade 3 allergic reaction/hypersensitivity or rash to thalidomide, that has not resolved to < grade 2

• Patients must not have any serious medical condition, laboratory abnormality, or psychiatric illness that, in the view of the treating physician, would place the participant at an unacceptable risk if he or she were to participate in the study or would prevent that person from giving informed consent

• Patients must not have history of thromboembolic event or other condition requiring current use of anticoagulation with Coumadin (warfarin) or low molecular-weight heparin

• Patients must not have known or suspected hypersensitivity to mannitol

• Patients must receive a 12-lead electrocardiogram (EKG), chest x-ray or computed tomography (CT) scan, serum creatinine, complete metabolic panel including serum glutamic oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT), electrolytes, and bilirubin testing within 28 days prior to registration in order to establish baseline measurements; questions regarding patient safety in regards to results of these tests should be directed to the study chair

• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to registration; FCBP must agree to have a second pregnancy test within 24 hours prior to starting cycle 1 if randomized to receive lenalidomide

• Further, patients commit to the following if they are randomized to receive lenalidomide: FCBP must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP, even if they have had a successful vasectomy; a FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months); all patients must be counseled by a trained counselor every 28 days about pregnancy precautions and risks of fetal exposure

• NOTE: Patients not randomized to receive lenalidomide will not be required to undergo serial pregnancy testing or lenalidomide counseling after registration

• No prior malignancy is allowed except for adequately treated basal cell (or squamous cell) skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for three years

• Cytogenetics requirements:

• Southwestern Oncology Group (SWOG) (and other sites not affiliated with Alliance or Eastern Cooperative Oncology Group [ECOG]-American College of Radiology Imaging Network [ACRIN]): Pretreatment cytogenetics must be performed on all patients; collection of pretreatment specimens must be completed within 30 days prior to registration to S1117; specimens must be submitted to the site's preferred Clinical Laboratory Improvement Amendments (CLIA)-approved cytogenetics laboratory; reports of the results must be submitted as described; note that cytogenetics are required at other timepoints; NOTE: National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) sites may submit specimens to College of American Pathologists (CAP) or Ontario Laboratory Accreditation (OLA)-approved laboratories providing the lab is licensed to perform fluorescent in situ hybridization (FISH) analysis

• Alliance: Alliance patients must enroll on Cancer and Leukemia Group B (CALGB) 8461, the cytogenetics protocol; CALGB 8461 provides sample procurement and submission instructions to Alliance-approved institutional cytogeneticists; note that cytogenetics are required at other timepoints

• ECOG-ACRIN: Pretreatment cytogenetics must be performed on all patients; collection of pretreatment specimens must be completed within 30 days prior to registration to S1117; specimens must be submitted to the site's preferred CLIA-approved cytogenetics laboratory; karyotypes and reports must be submitted for review to the Mayo Clinic Cytogenetics Laboratory in Rochester; note that cytogenetics testing is required at other timepoints

• Banking requirements:

• SWOG, Alliance and ECOG-ACRIN (and other sites not affiliated with NCIC CTG):

Patients must be offered participation in specimen banking; with patient consent, specimens must be submitted as outlined

• Alliance: (Temporarily Closed 2/28/14): As of February 28, 2014, CALGB 9665 has been temporarily closed, so Alliance patients under consideration for S1117 are NOT to be registered to CALGB 9665 and no specimens for patients enrolled after February 28, 2014 are to be submitted via this ancillary study; these patients should submit specimens per SWOG instructions; patients already enrolled on CALGB 9665 should continue to submit specimens per instructions in CALGB 9665

• NCIC CTG: NCIC CTG patients must be offered participation in specimen submission and banking; with patient consent, specimens must be submitted as outlined

• All patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

• As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

Related Conditions & MeSH terms

• Anemia, Refractory, with Excess of Blasts
• Chronic Myelomonocytic Leukemia
• Chronic Myelomonocytic Leukemia-1
• Chronic Myelomonocytic Leukemia-2
• Leukemia
• Leukemia, Myelomonocytic, Acute
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Myelodysplastic Syndrome
• Myelodysplastic Syndrome With Excess Blasts
• Myelodysplastic Syndrome With Excess Blasts-1
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• Azacitidine
Given SC or IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Lenalidomide
Given PO
• Vorinostat
Given PO

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	CSSS Champlain-Charles Le Moyne	Greenfield Park	Quebec
Canada	QEII Health Sciences Centre/Nova Scotia Health Authority	Halifax	Nova Scotia
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	The Moncton Hospital	Moncton	New Brunswick
Canada	McGill University Department of Oncology	Montreal	Quebec
Canada	The Research Institute of the McGill University Health Centre (MUHC)	Montreal	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Atlantic Health Sciences Corporation-Saint John Regional Hospital	Saint John	New Brunswick
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Odette Cancer Centre- Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	University Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	Clinical Research Unit at Vancouver Coastal Health Authority	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
United States	Presbyterian Kaseman Hospital	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	The Don and Sybil Harrington Cancer Center	Amarillo	Texas
United States	McFarland Clinic - Ames	Ames	Iowa
United States	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan
United States	Trinity Health Saint Joseph Mercy Hospital Ann Arbor	Ann Arbor	Michigan
United States	Kaiser Permanente-Deer Valley Medical Center	Antioch	California
United States	Randolph Hospital	Asheboro	North Carolina
United States	Augusta University Medical Center	Augusta	Georgia
United States	The Medical Center of Aurora	Aurora	Colorado
United States	UCHealth University of Colorado Hospital	Aurora	Colorado
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Ochsner Health Center-Summa	Baton Rouge	Louisiana
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	Cleveland Clinic Cancer Center Beachwood	Beachwood	Ohio
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Billings Clinic Cancer Center	Billings	Montana
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Mid Dakota Clinic	Bismarck	North Dakota
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Boulder Community Hospital	Boulder	Colorado
United States	Bozeman Health Deaconess Hospital	Bozeman	Montana
United States	Steward Saint Elizabeth's Medical Center	Brighton	Massachusetts
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Montefiore Medical Center-Weiler Hospital	Bronx	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Carlisle Regional Cancer Center	Carlisle	Pennsylvania
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Roper Hospital	Charleston	South Carolina
United States	Hematology and Oncology Associates	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin
United States	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	MU Health - University Hospital/Ellis Fischel Cancer Center	Columbia	Missouri
United States	Veterans Administration	Columbia	Missouri
United States	Columbus NCI Community Oncology Research Program	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Miami Valley Hospital	Dayton	Ohio
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Heartland Cancer Research NCORP	Decatur	Illinois
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Midtown	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Rose	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	SCL Health Saint Joseph Hospital	Denver	Colorado
United States	Western States Cancer Research NCORP	Denver	Colorado
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Doylestown Hospital	Doylestown	Pennsylvania
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Mercy Medical Center	Durango	Colorado
United States	HSHS Sacred Heart Hospital	Eau Claire	Wisconsin
United States	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Christiana Care - Union Hospital	Elkton	Maryland
United States	Mountain Blue Cancer Care Center - Swedish	Englewood	Colorado
United States	Swedish Medical Center	Englewood	Colorado
United States	OSF Saint Francis Hospital and Medical Group	Escanaba	Michigan
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Clinic North-Fargo	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	University of Connecticut	Farmington	Connecticut
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Unity Hospital	Fridley	Minnesota
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Mountain Blue Cancer Care Center	Golden	Colorado
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan
United States	Corewell Health Grand Rapids Hospitals - Butterworth Hospital	Grand Rapids	Michigan
United States	Trinity Health Grand Rapids Hospital	Grand Rapids	Michigan
United States	Banner North Colorado Medical Center	Greeley	Colorado
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	Cone Health Cancer Center	Greensboro	North Carolina
United States	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Rocky Mountain Cancer Centers-Greenwood Village	Greenwood Village	Colorado
United States	Legacy Mount Hood Medical Center	Gresham	Oregon
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Illinois CancerCare-Havana	Havana	Illinois
United States	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania
United States	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii
United States	Kaiser Permanente Moanalua Medical Center	Honolulu	Hawaii
United States	Queen's Cancer Center - Kuakini	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Cleveland Clinic Cancer Center Independence	Independence	Ohio
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Mercyhealth Hospital and Cancer Center - Janesville	Janesville	Wisconsin
United States	Jupiter Medical Center	Jupiter	Florida
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	ECU Health Oncology Kinston	Kinston	North Carolina
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Northwell Health/Center for Advanced Medicine	Lake Success	New York
United States	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Beebe Medical Center	Lewes	Delaware
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	John L McClellan Memorial Veterans Hospital	Little Rock	Arkansas
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Longmont United Hospital	Longmont	Colorado
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Banner McKee Medical Center	Loveland	Colorado
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	SSM Health Dean Medical Group - South Madison Campus	Madison	Wisconsin
United States	North Shore University Hospital	Manhasset	New York
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin
United States	Bay Area Medical Center	Marinette	Wisconsin
United States	Marshfield Medical Center	Marshfield	Wisconsin
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Sovah Health Martinsville	Martinsville	Virginia
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	Premier Oncology Hematology Associates	Merrillville	Indiana
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Providence Milwaukie Hospital	Milwaukie	Oregon
United States	NYU Langone Hospital - Long Island	Mineola	New York
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Minneapolis VA Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	University of South Alabama Mitchell Cancer Institute	Mobile	Alabama
United States	Trinity Medical Center	Moline	Illinois
United States	Illinois CancerCare-Monmouth	Monmouth	Illinois
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	Trinity Health Muskegon Hospital	Muskegon	Michigan
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	NYP/Weill Cornell Medical Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Licking Memorial Hospital	Newark	Ohio
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Illinois CancerCare-Community Cancer Center	Normal	Illinois
United States	Cancer Care Associates-Norman	Norman	Oklahoma
United States	Kaiser Permanente-Oakland	Oakland	California
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Oconto Falls	Oconto Falls	Wisconsin
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Providence Willamette Falls Medical Center	Oregon City	Oregon
United States	AdventHealth Orlando	Orlando	Florida
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	Parker Adventist Hospital	Parker	Colorado
United States	Rocky Mountain Cancer Centers-Parker	Parker	Colorado
United States	University Hospitals Parma Medical Center	Parma	Ohio
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	FirstHealth of the Carolinas-Moore Regional Hospital	Pinehurst	North Carolina
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	Lake Huron Medical Center	Port Huron	Michigan
United States	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Kansas City NCI Community Oncology Research Program	Prairie Village	Kansas
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Corewell Health Reed City Hospital	Reed City	Michigan
United States	Annie Penn Memorial Hospital	Reidsville	North Carolina
United States	Ascension Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	Kaiser Permanente-Richmond	Richmond	California
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Swedish American Hospital	Rockford	Illinois
United States	UW Health Carbone Cancer Center Rockford	Rockford	Illinois
United States	Kaiser Permanente - Sacramento	Sacramento	California
United States	Kaiser Permanente-South Sacramento	Sacramento	California
United States	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Saint Louis-Cape Girardeau CCOP	Saint Louis	Missouri
United States	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Kaiser Permanente-San Francisco	San Francisco	California
United States	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California
United States	Kaiser Permanente-San Rafael	San Rafael	California
United States	North Coast Cancer Care	Sandusky	Ohio
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Kaiser Permanente-Santa Rosa	Santa Rosa	California
United States	Sutter Pacific Medical Foundation	Santa Rosa	California
United States	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	LSU Health Sciences Center at Shreveport	Shreveport	Louisiana
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Baystate Medical Center	Springfield	Massachusetts
United States	Memorial Medical Center	Springfield	Illinois
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Iredell Memorial Hospital	Statesville	North Carolina
United States	Ascension Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Cleveland Clinic Cancer Center Strongsville	Strongsville	Ohio
United States	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Aurora Medical Center in Summit	Summit	Wisconsin
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	University of Toledo	Toledo	Ohio
United States	Cotton O'Neil Cancer Center / Stormont Vail Health	Topeka	Kansas
United States	Munson Medical Center	Traverse City	Michigan
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	University of Arizona Cancer Center-North Campus	Tucson	Arizona
United States	Carle Cancer Center	Urbana	Illinois
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Sibley Memorial Hospital	Washington	District of Columbia
United States	Veterans Affairs Medical Center -Washington DC	Washington	District of Columbia
United States	MercyOne Waterloo Cancer Center	Waterloo	Iowa
United States	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin
United States	Reading Hospital	West Reading	Pennsylvania
United States	Saint Ann's Hospital	Westerville	Ohio
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Southeast Clinical Oncology Research Consortium NCORP	Winston-Salem	North Carolina
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio
United States	UMass Memorial Medical Center - University Campus	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response Rate (Phase II)	A response is any of complete hematological remission, partial remission, or hematologic improvement.	Up to 5 years
Primary	Overall Survival (Phase III)	OS is calculated for all patients from the date of initial registration to date of death due to any cause. The follow-up for patients last known to be alive is censored at the date of last contact. Stratified Cox regression models will be used to compare OS of the combination arm selected in the Phase II portion of the trial to OS of the single-agent azacitidine arm.	Up to 5 years
Secondary	Relapse-free Survival	RFS is calculated for patients who have achieved a response. RFS will be measured from the date of response to the date of first documentation of relapse from response (as defined in the primary objective), or death due to any cause. The follow-up for patients last known to be alive and without report of relapse is censored at the date of last contact. RFS will be estimated for each of the three arms using the Kaplan-Meier method.	Up to 5 years
Secondary	Overall Survival	OS is calculated for all patients from the date of initial registration to date of death due to any cause. The follow- up for patients last known to be alive is censored at the date of last contact. OS will be estimated for each of the three arms using the Kaplan-Meier method.	Up to 5 years
Secondary	Pre-study Cytogenetic Abnormalities	Cytogenetic risk group is used to identify cytogenetic abnormalities.	Up to 5 years
Secondary	Toxicity Rate	Adverse events that are possibly, probably or definitely related to study drug are reported.	Up to 5 years