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

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome; Myelodysplastic Syndrome With Excess Blasts; Chronic Myelomonocytic Leukemia-1; Chronic Myelomonocytic Leukemia-2; Myelodysplastic Syndrome With Excess Blasts-1; Myelodysplastic Syndrome/Acute Myeloid Leukemia
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Azacitidine; Drug: Lenalidomide; Drug: Vorinostat

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 282
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 3P1
      • Clinical Research Unit at Vancouver Coastal Health Authority
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6Z8
      • The Moncton Hospital
    • Saint John, New Brunswick, Canada, E2L 4L2
      • Atlantic Health Sciences Corporation-Saint John Regional Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • QEII Health Sciences Centre/Nova Scotia Health Authority
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre at Hamilton Health Sciences
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network-Princess Margaret Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Odette Cancer Centre- Sunnybrook Health Sciences Centre
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • CSSS Champlain-Charles Le Moyne
    • Montreal, Quebec, Canada, H3H 2R9
      • The Research Institute of the McGill University Health Centre (MUHC)
    • Montreal, Quebec, Canada, H2W 1S6
      • McGill University Department of Oncology
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham Cancer Center
    • Mobile, Alabama, United States, 36688
      • University of South Alabama Mitchell Cancer Institute
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
    • Tucson, Arizona, United States, 85719
      • Banner University Medical Center - Tucson
    • Tucson, Arizona, United States, 85719
      • University of Arizona Cancer Center-North Campus
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • John L McClellan Memorial Veterans Hospital
  • California
    • Antioch, California, United States, 94531
      • Kaiser Permanente-Deer Valley Medical Center
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center
    • Oakland, California, United States, 94611
      • Kaiser Permanente-Oakland
    • Palo Alto, California, United States, 94304
      • Stanford Cancer Institute Palo Alto
    • Richmond, California, United States, 94801
      • Kaiser Permanente-Richmond
    • Sacramento, California, United States, 95823
      • Kaiser Permanente-South Sacramento
    • Sacramento, California, United States, 95825
      • Kaiser Permanente - Sacramento
    • San Francisco, California, United States, 94115
      • Kaiser Permanente-San Francisco
    • San Jose, California, United States, 95119
      • Kaiser Permanente-Santa Teresa-San Jose
    • San Rafael, California, United States, 94903
      • Kaiser Permanente-San Rafael
    • Santa Clara, California, United States, 95051
      • Kaiser Permanente Medical Center - Santa Clara
    • Santa Rosa, California, United States, 95403
      • Kaiser Permanente-Santa Rosa
    • Santa Rosa, California, United States, 95403
      • Sutter Pacific Medical Foundation
    • South San Francisco, California, United States, 94080
      • Kaiser Permanente-South San Francisco
    • Vallejo, California, United States, 94589
      • Kaiser Permanente-Vallejo
    • Walnut Creek, California, United States, 94596
      • Kaiser Permanente-Walnut Creek
  • Colorado
    • Aurora, Colorado, United States, 80012
      • The Medical Center of Aurora
    • Aurora, Colorado, United States, 80045
      • UCHealth University of Colorado Hospital
    • Boulder, Colorado, United States, 80301
      • Boulder Community Hospital
    • Colorado Springs, Colorado, United States, 80907
      • Penrose-Saint Francis Healthcare
    • Denver, Colorado, United States, 80210
      • Porter Adventist Hospital
    • Denver, Colorado, United States, 80218
      • Presbyterian - Saint Lukes Medical Center - Health One
    • Denver, Colorado, United States, 80218
      • SCL Health Saint Joseph Hospital
    • Denver, Colorado, United States, 80220
      • Rose Medical Center
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Centers-Midtown
    • Denver, Colorado, United States, 80220
      • Rocky Mountain Cancer Centers-Rose
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
    • Denver, Colorado, United States, 80222
      • Western States Cancer Research NCORP
    • Durango, Colorado, United States, 81301
      • Mercy Medical Center
    • Englewood, Colorado, United States, 80113
      • Mountain Blue Cancer Care Center - Swedish
    • Englewood, Colorado, United States, 80113
      • Swedish Medical Center
    • Fort Collins, Colorado, United States, 80524
      • Poudre Valley Hospital
    • Golden, Colorado, United States, 80401
      • Mountain Blue Cancer Care Center
    • Greeley, Colorado, United States, 80631
      • North Colorado Medical Center
    • Greenwood Village, Colorado, United States, 80111
      • Rocky Mountain Cancer Centers-Greenwood Village
    • Lakewood, Colorado, United States, 80228
      • Saint Anthony Hospital
    • Lakewood, Colorado, United States, 80228
      • Rocky Mountain Cancer Centers-Lakewood
    • Littleton, Colorado, United States, 80122
      • Littleton Adventist Hospital
    • Lone Tree, Colorado, United States, 80124
      • Sky Ridge Medical Center
    • Lone Tree, Colorado, United States, 80124
      • Rocky Mountain Cancer Centers-Sky Ridge
    • Longmont, Colorado, United States, 80501
      • Longmont United Hospital
    • Loveland, Colorado, United States, 80539
      • McKee Medical Center
    • Parker, Colorado, United States, 80138
      • Parker Adventist Hospital
    • Parker, Colorado, United States, 80138
      • Rocky Mountain Cancer Centers-Parker
    • Pueblo, Colorado, United States, 81004
      • Saint Mary Corwin Medical Center
    • Wheat Ridge, Colorado, United States, 80033
      • SCL Health Lutheran Medical Center
  • Connecticut
    • Farmington, Connecticut, United States, 06030
      • University of Connecticut
    • Hartford, Connecticut, United States, 06105
      • Smilow Cancer Hospital Care Center at Saint Francis
    • New Britain, Connecticut, United States, 06050
      • The Hospital of Central Connecticut
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Beebe Medical Center
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20016
      • Sibley Memorial Hospital
    • Washington, District of Columbia, United States, 20422
      • Veterans Affairs Medical Center -Washington DC
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida Health Science Center - Gainesville
    • Jupiter, Florida, United States, 33458
      • Jupiter Medical Center
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Medical Center
    • Orlando, Florida, United States, 32803
      • AdventHealth Orlando
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University Medical Center
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Hawaii Cancer Care Inc - Waterfront Plaza
    • Honolulu, Hawaii, United States, 96813
      • Straub Clinic and Hospital
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii Cancer Center
    • Honolulu, Hawaii, United States, 96817
      • Queen's Cancer Center - Kuakini
    • Honolulu, Hawaii, United States, 96819
      • Kaiser Permanente Moanalua Medical Center
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center-Boise
    • Post Falls, Idaho, United States, 83854
      • Kootenai Clinic Cancer Services - Post Falls
  • Illinois
    • Bloomington, Illinois, United States, 61704
      • Illinois CancerCare-Bloomington
    • Canton, Illinois, United States, 61520
      • Illinois CancerCare-Canton
    • Carthage, Illinois, United States, 62321
      • Illinois CancerCare-Carthage
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Chicago, Illinois, United States, 60612
      • University of Illinois
    • Chicago, Illinois, United States, 60611
      • Hematology and Oncology Associates
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Heartland Cancer Research NCORP
    • Eureka, Illinois, United States, 61530
      • Illinois CancerCare-Eureka
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem-Evanston Hospital
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare-Galesburg
    • Havana, Illinois, United States, 62644
      • Illinois CancerCare-Havana
    • Kewanee, Illinois, United States, 61443
      • Illinois CancerCare-Kewanee Clinic
    • Macomb, Illinois, United States, 61455
      • Illinois CancerCare-Macomb
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Moline, Illinois, United States, 61265
      • Trinity Medical Center
    • Monmouth, Illinois, United States, 61462
      • Illinois CancerCare-Monmouth
    • Normal, Illinois, United States, 61761
      • Illinois CancerCare-Community Cancer Center
    • Ottawa, Illinois, United States, 61350
      • Illinois CancerCare-Ottawa Clinic
    • Pekin, Illinois, United States, 61554
      • Illinois CancerCare-Pekin
    • Peoria, Illinois, United States, 61615
      • Illinois CancerCare-Peoria
    • Peru, Illinois, United States, 61354
      • Illinois CancerCare-Peru
    • Princeton, Illinois, United States, 61356
      • Illinois CancerCare-Princeton
    • Rockford, Illinois, United States, 61114
      • SwedishAmerican Regional Cancer Center/ACT
    • Rockford, Illinois, United States, 61104
      • Swedish American Hospital
    • Springfield, Illinois, United States, 62781
      • Memorial Medical Center
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
  • Indiana
    • Merrillville, Indiana, United States, 46410
      • Premier Oncology Hematology Associates
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic - Ames
    • Iowa City, Iowa, United States, 52242
      • University of Iowa/Holden Comprehensive Cancer Center
    • Sioux City, Iowa, United States, 51101
      • Siouxland Regional Cancer Center
    • Waterloo, Iowa, United States, 50702
      • MercyOne Waterloo Cancer Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center
    • Prairie Village, Kansas, United States, 66208
      • Kansas City NCI Community Oncology Research Program
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Cancer Center / Stormont Vail Health
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky/Markey Cancer Center
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Ochsner Health Center-Summa
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center Jefferson
    • Shreveport, Louisiana, United States, 71103
      • LSU Health Sciences Center at Shreveport
  • Maine
    • Bangor, Maine, United States, 04401
      • Eastern Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University/Sidney Kimmel Cancer Center
    • Elkton, Maryland, United States, 21921
      • Christiana Care - Union Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
    • Brighton, Massachusetts, United States, 02135
      • Steward Saint Elizabeth's Medical Center
    • Springfield, Massachusetts, United States, 01199
      • Baystate Medical Center
    • Worcester, Massachusetts, United States, 01655
      • UMass Memorial Medical Center - University Campus
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • Saint Joseph Mercy Hospital
    • Ann Arbor, Michigan, United States, 48106
      • Michigan Cancer Research Consortium NCORP
    • Battle Creek, Michigan, United States, 49017
      • Bronson Battle Creek
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Karmanos Cancer Institute
    • Detroit, Michigan, United States, 48236
      • Ascension Saint John Hospital
    • Escanaba, Michigan, United States, 49829
      • Green Bay Oncology - Escanaba
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health at Butterworth Campus
    • Grand Rapids, Michigan, United States, 49503
      • Cancer Research Consortium of West Michigan NCORP
    • Grand Rapids, Michigan, United States, 49503
      • Trinity Health Grand Rapids Hospital
    • Iron Mountain, Michigan, United States, 49801
      • Green Bay Oncology - Iron Mountain
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Muskegon, Michigan, United States, 49444
      • Trinity Health Muskegon Hospital
    • Port Huron, Michigan, United States, 48060
      • Lake Huron Medical Center
    • Reed City, Michigan, United States, 49677
      • Corewell Health Reed City Hospital
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
    • Warren, Michigan, United States, 48093
      • Saint John Macomb-Oakland Hospital
  • Minnesota
    • Bemidji, Minnesota, United States, 56601
      • Sanford Joe Lueken Cancer Center
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Duluth, Minnesota, United States, 55805
      • Essentia Health Cancer Center
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fridley, Minnesota, United States, 55432
      • Unity Hospital
    • Hutchinson, Minnesota, United States, 55350
      • Hutchinson Area Health Care
    • Maplewood, Minnesota, United States, 55109
      • Saint John's Hospital - Healtheast
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology PA-Maplewood
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
    • Minneapolis, Minnesota, United States, 55417
      • Minneapolis VA Medical Center
    • Robbinsdale, Minnesota, United States, 55422
      • North Memorial Medical Health Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
    • Saint Cloud, Minnesota, United States, 56303
      • Coborn Cancer Center at Saint Cloud Hospital
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
    • Saint Louis Park, Minnesota, United States, 55416
      • Metro Minnesota Community Oncology Research Consortium
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Shakopee, Minnesota, United States, 55379
      • Saint Francis Regional Medical Center
    • Stillwater, Minnesota, United States, 55082
      • Lakeview Hospital
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
    • Willmar, Minnesota, United States, 56201
      • Rice Memorial Hospital
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology Hematology PA-Woodbury
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • Columbia, Missouri, United States, 65201
      • Veterans Administration
    • Columbia, Missouri, United States, 65212
      • MU Health - University Hospital/Ellis Fischel Cancer Center
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital of Kansas City
    • Saint Louis, Missouri, United States, 63141
      • Mercy Hospital Saint Louis
    • Saint Louis, Missouri, United States, 63141
      • Saint Louis-Cape Girardeau CCOP
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic Cancer Center
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Hospital
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • University of New Mexico Cancer Center
    • Albuquerque, New Mexico, United States, 87110
      • Presbyterian Kaseman Hospital
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center - Moses Campus
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center-Weiler Hospital
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Lake Success, New York, United States, 11042
      • Northwell Health/Center for Advanced Medicine
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
    • Mineola, New York, United States, 11501
      • NYU Winthrop Hospital
    • New York, New York, United States, 10065
      • NYP/Weill Cornell Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Asheboro, North Carolina, United States, 27203
      • Randolph Hospital
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital
    • Greensboro, North Carolina, United States, 27403
      • Cone Health Cancer Center
    • Hendersonville, North Carolina, United States, 28791
      • Margaret R Pardee Memorial Hospital
    • Kinston, North Carolina, United States, 28501
      • Vidant Oncology-Kinston
    • Pinehurst, North Carolina, United States, 28374
      • FirstHealth of the Carolinas-Moore Regional Hospital
    • Reidsville, North Carolina, United States, 27320
      • Annie Penn Memorial Hospital
    • Statesville, North Carolina, United States, 28677
      • Iredell Memorial Hospital
    • Winston-Salem, North Carolina, United States, 27104
      • Southeast Clinical Oncology Research Consortium NCORP
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Sanford Bismarck Medical Center
    • Bismarck, North Dakota, United States, 58501
      • Mid Dakota Clinic
    • Fargo, North Dakota, United States, 58122
      • Sanford Roger Maris Cancer Center
    • Fargo, North Dakota, United States, 58122
      • Sanford Broadway Medical Center
    • Fargo, North Dakota, United States, 58122
      • Sanford Clinic North-Fargo
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • Cleveland Clinic Cancer Center Beachwood
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Cancer Center-UC Medical Center
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Cancer Center/Fairview Hospital
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Columbus, Ohio, United States, 43219
      • The Mark H Zangmeister Center
    • Columbus, Ohio, United States, 43222
      • Mount Carmel Health Center West
    • Columbus, Ohio, United States, 43215
      • Columbus NCI Community Oncology Research Program
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Independence, Ohio, United States, 44131
      • Cleveland Clinic Cancer Center Independence
    • Marietta, Ohio, United States, 45750
      • Marietta Memorial Hospital
    • Mayfield Heights, Ohio, United States, 44124
      • Hillcrest Hospital Cancer Center
    • Newark, Ohio, United States, 43055
      • Licking Memorial Hospital
    • Parma, Ohio, United States, 44129
      • University Hospitals Parma Medical Center
    • Sandusky, Ohio, United States, 44870
      • North Coast Cancer Care
    • Springfield, Ohio, United States, 45505
      • Springfield Regional Medical Center
    • Strongsville, Ohio, United States, 44136
      • Cleveland Clinic Cancer Center Strongsville
    • Sylvania, Ohio, United States, 43560
      • ProMedica Flower Hospital
    • Toledo, Ohio, United States, 43614
      • University of Toledo
    • Westerville, Ohio, United States, 43081
      • Saint Ann's Hospital
    • Wooster, Ohio, United States, 44691
      • Cleveland Clinic Wooster Family Health and Surgery Center
  • Oklahoma
    • Norman, Oklahoma, United States, 73071
      • Cancer Care Associates-Norman
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Oklahoma City, Oklahoma, United States, 73120
      • Mercy Hospital Oklahoma City
  • Oregon
    • Gresham, Oregon, United States, 97030
      • Legacy Mount Hood Medical Center
    • Milwaukie, Oregon, United States, 97222
      • Providence Milwaukie Hospital
    • Newberg, Oregon, United States, 97132
      • Providence Newberg Medical Center
    • Oregon City, Oregon, United States, 97045
      • Providence Willamette Falls Medical Center
    • Portland, Oregon, United States, 97210
      • Legacy Good Samaritan Hospital and Medical Center
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97225
      • Providence Saint Vincent Medical Center
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Hospital-Cedar Crest
    • Carlisle, Pennsylvania, United States, 17015
      • Carlisle Regional Cancer Center
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Doylestown, Pennsylvania, United States, 18901
      • Doylestown Hospital
    • Hazleton, Pennsylvania, United States, 18201
      • Geisinger Medical Center-Cancer Center Hazleton
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Milton S Hershey Medical Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute (UPCI)
    • Sayre, Pennsylvania, United States, 18840
      • Guthrie Medical Group PC-Robert Packer Hospital
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Geisinger Wyoming Valley/Henry Cancer Center
  • South Carolina
    • Boiling Springs, South Carolina, United States, 29316
      • Prisma Health Cancer Institute - Spartanburg
    • Charleston, South Carolina, United States, 29401
      • Roper Hospital
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Cancer Institute - Faris
    • Greenville, South Carolina, United States, 29615
      • Prisma Health Cancer Institute - Eastside
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Cancer Institute - Butternut
    • Greenville, South Carolina, United States, 29601
      • Saint Francis Hospital
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Greenville Memorial Hospital
    • Seneca, South Carolina, United States, 29672
      • Prisma Health Cancer Institute - Seneca
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Center
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Regional Hospital
    • Sioux Falls, South Dakota, United States, 57117-5134
      • Sanford USD Medical Center - Sioux Falls
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Cancer Center Oncology Clinic
  • Tennessee
    • Knoxville, Tennessee, United States, 37916
      • Thompson Cancer Survival Center
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University/Ingram Cancer Center
  • Texas
    • Amarillo, Texas, United States, 79106
      • The Don and Sybil Harrington Cancer Center
    • Dallas, Texas, United States, 75390
      • UT Southwestern/Simmons Cancer Center-Dallas
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
  • Virginia
    • Martinsville, Virginia, United States, 24115
      • Sovah Health Martinsville
  • Washington
    • Vancouver, Washington, United States, 98664
      • PeaceHealth Southwest Medical Center
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Healthcare
  • Wisconsin
    • Chippewa Falls, Wisconsin, United States, 54729
      • Marshfield Clinic-Chippewa Center
    • Eau Claire, Wisconsin, United States, 54701
      • HSHS Sacred Heart Hospital
    • Eau Claire, Wisconsin, United States, 54701
      • Marshfield Clinic Cancer Center at Sacred Heart
    • Green Bay, Wisconsin, United States, 54311
      • Aurora BayCare Medical Center
    • Green Bay, Wisconsin, United States, 54301
      • Saint Vincent Hospital Cancer Center Green Bay
    • Green Bay, Wisconsin, United States, 54303
      • Saint Vincent Hospital Cancer Center at Saint Mary's
    • Green Bay, Wisconsin, United States, 54303
      • Green Bay Oncology Limited at Saint Mary's Hospital
    • Green Bay, Wisconsin, United States, 54301-3526
      • Green Bay Oncology at Saint Vincent Hospital
    • Janesville, Wisconsin, United States, 53548
      • Mercyhealth Hospital and Cancer Center - Janesville
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Medical Center
    • Madison, Wisconsin, United States, 53717
      • Dean Hematology and Oncology Clinic
    • Marinette, Wisconsin, United States, 54143
      • Aurora Bay Area Medical Group-Marinette
    • Marinette, Wisconsin, United States, 54143
      • Bay Area Medical Center
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Medical Center-Marshfield
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Medical Center
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College Of Wisconsin
    • Minocqua, Wisconsin, United States, 54548
      • Marshfield Clinic-Minocqua Center
    • Oconomowoc, Wisconsin, United States, 53066
      • ProHealth Oconomowoc Memorial Hospital
    • Oconto Falls, Wisconsin, United States, 54154
      • Saint Vincent Hospital Cancer Center at Oconto Falls
    • Rhinelander, Wisconsin, United States, 54501
      • Ascension Saint Mary's Hospital
    • Rice Lake, Wisconsin, United States, 54868
      • Marshfield Medical Center-Rice Lake
    • Stevens Point, Wisconsin, United States, 54481
      • Ascension Saint Michael's Hospital
    • Sturgeon Bay, Wisconsin, United States, 54235
      • Green Bay Oncology - Sturgeon Bay
    • Summit, Wisconsin, United States, 53066
      • Aurora Medical Center in Summit
    • Waukesha, Wisconsin, United States, 53188
      • ProHealth Waukesha Memorial Hospital
    • Wauwatosa, Wisconsin, United States, 53226
      • Aurora Cancer Care-Milwaukee West
    • Weston, Wisconsin, United States, 54476
      • Marshfield Medical Center - Weston
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Marshfield Clinic - Wisconsin Rapids Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (azacitidine and lenalidomide); Patients receive azacitidine SC or IV on days 1-7 or days 1-5 and 8-9, and lenalidomide PO QD on days 1-21. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Azacitidine; Given SC or IV; Other Names: 5 AZC; 5-AC; 5-Azacytidine; 5-AZC; Azacytidine; Azacytidine, 5-; Ladakamycin; Mylosar; U-18496; Vidaza; 5-Azacitidine; Drug: Lenalidomide; Given PO; Other Names: CC-5013; Revlimid; CC5013; CDC 501
Experimental: Arm II (azacitidine); Patients receive azacitidine as in Arm I. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Azacitidine; Given SC or IV; Other Names: 5 AZC; 5-AC; 5-Azacytidine; 5-AZC; Azacytidine; Azacytidine, 5-; Ladakamycin; Mylosar; U-18496; Vidaza; 5-Azacitidine
Experimental: Arm III (azacitidine and vorinostat); Patients receive azacitidine as in Arm I and vorinostat PO BID on days 3-9. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Azacitidine; Given SC or IV; Other Names: 5 AZC; 5-AC; 5-Azacytidine; 5-AZC; Azacytidine; Azacytidine, 5-; Ladakamycin; Mylosar; U-18496; Vidaza; 5-Azacitidine; Drug: Vorinostat; Given PO; Other Names: SAHA; Suberoylanilide Hydroxamic Acid; MSK-390; Zolinza; L-001079038; Suberanilohydroxamic Acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate (Phase II)	A response is any of complete hematological remission, partial remission, or hematologic improvement.	Up to 5 years
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Pre-study Cytogenetic Abnormalities	Cytogenetic risk group is used to identify cytogenetic abnormalities.	Up to 5 years
Toxicity Rate	Adverse events that are possibly, probably or definitely related to study drug are reported.	Up to 5 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Mikkael A Sekeres, SWOG Cancer Research Network

Publications and helpful links

General Publications

• Statler A, Othus M, Erba HP, Chauncey TR, Radich JP, Coutre S, Advani A, Nand S, Ravandi F, Mukherjee S, Sekeres MA. Comparable outcomes of patients eligible vs ineligible for SWOG leukemia studies. Blood. 2018 Jun 21;131(25):2782-2788. doi: 10.1182/blood-2018-01-826693. Epub 2018 Apr 4.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2012
• Primary Completion (Actual): June 1, 2015
• Study Completion (Estimated): March 7, 2025

Study Registration Dates

• First Submitted: January 27, 2012
• First Submitted That Met QC Criteria: January 27, 2012
• First Posted (Estimated): February 1, 2012

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Disease; Bone Marrow Diseases; Hematologic Diseases; Anemia; Precancerous Conditions; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Myeloid; Anemia, Refractory; Chronic Disease; Syndrome; Myelodysplastic Syndromes; Leukemia; Preleukemia; Leukemia, Myelomonocytic, Acute; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Anemia, Refractory, with Excess of Blasts; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Histone Deacetylase Inhibitors; Lenalidomide; Azacitidine; Vorinostat
• Other Study ID Numbers: NCI-2012-00242 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA032102 (U.S. NIH Grant/Contract); U10CA180888 (U.S. NIH Grant/Contract); CDR0000723909; SWOG-S1117; S1117 (Other Identifier: CTEP)