RATIONALE: Giving chemotherapy drugs, such as R115777, isotretinoin, cytarabine, and
fludarabine, before a donor bone marrow transplant or an umbilical cord transplant helps stop
the growth of cancer cells. It also helps stop the patient's immune system from rejecting the
donor's stem cells. When the healthy stem cells from a donor are infused into the patient
they may help the patient's bone marrow make stem cells, red blood cells, white blood cells,
and platelets.
PURPOSE: This phase II trial is studying how well giving combination chemotherapy together
with donor bone marrow or umbilical cord blood transplant works in treating children with
newly diagnosed juvenile myelomonocytic leukemia.
- Determine the response rate of children with newly diagnosed juvenile myelomonocytic
leukemia treated with R115777, isotretinoin, cytarabine, and fludarabine followed by
allogeneic bone marrow or umbilical cord blood transplantation. (R11577 portion of the
study closed to accrual as of 08/2005)
- Determine the safety and toxicity of this regimen in these patients.
- Determine the tolerability of this regimen in these patients.
- Determine the rate of 2-year event-free survival of patients treated with this regimen.
- Determine whether prognostic subsets of these patients can be identified based on
expression of clinical, genetic (NFI, monosomy 7, RAS gene), or hematopoietic
characteristics.
Patients may choose to receive upfront window induction therapy with oral R115777 twice daily
on days 1-21. Treatment repeats every 28 days for 2 courses in the absence of disease
progression or unacceptable toxicity. Patients with progressive disease or stable disease
with unacceptable hematopoietic recovery after 1 course proceed to induction chemotherapy.
(R11577 portion of the study closed to accrual as of 08/2005)
All patients receive induction chemotherapy comprising oral isotretinoin once daily beginning
on day 1 and fludarabine IV over 30 minutes and cytarabine IV over 4 hours on days 1-5.
Treatment with fludarabine and cytarabine repeats every 28 days for 2 courses. Treatment with
isotretinoin continues until allogeneic bone marrow or umbilical cord blood transplantation.
Patients with progressive disease after 1 course proceed to transplantation.
After completion of isotretinoin, patients receive a preparative regimen comprising total
body irradiation twice daily on days - 7 to -4, cyclophosphamide IV over 2 hours on days -3
and - 2, and anti-thymocyte globulin IV over 4-6 hours every 12 hours on days -3 to -1.
Patients undergo allogeneic bone marrow or umbilical cord blood transplantation on day 0.
Patients receive oral isotretinoin daily beginning on approximately day 60 and continuing for
1 year.
Patients are followed every 6 months for 5 years and then annually thereafter.
PROJECTED ACCRUAL: A maximum of 100 patients (18-46 receiving R115777 with induction
chemotherapy [R11577 portion of the study closed to accrual as of 08/2005] and 27-54
receiving induction chemotherapy only) will be accrued for this study within 3. 2 years.
Starship Children's Health, Auckland 1, New Zealand
San Jorge Children's Hospital, Santurce 00912, Puerto Rico
University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, Alabama 35294, United States
Alberta Children's Hospital, Calgary, Alberta T3B 6A8, Canada
Phoenix Children's Hospital, Phoenix, Arizona 85016-7710, United States
Children's & Women's Hospital of British Columbia, Vancouver, British Columbia V6H 3V4, Canada
Children's Hospital and Health Center - San Diego, San Diego, California 92123-4282, United States
Children's Hospital and Research Center - Oakland, Oakland, California 94609-1809, United States
Children's Hospital Central California, Madera, California 93638-8762, United States
Children's Hospital of Orange County, Orange, California 92868, United States
Jonathan Jaques Children's Cancer Center at Miller Children's Hospital, Long Beach, California 90801, United States
Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, California 90095-1781, United States
Kaiser Permanente Medical Center - Oakland, Sacramento, California 95825, United States
Loma Linda University Cancer Institute at Loma Linda University Medical Center, Loma Linda, California 92354, United States
Southern California Permanente Medical Group, Downey, California 90242-2814, United States
Stanford Comprehensive Cancer Center at Stanford University Medical Center, Stanford, California 94305, United States
Sutter Cancer Center, Sacramento, California 95816, United States
UCSF Comprehensive Cancer Center, San Francisco, California 94115, United States
University of California Davis Cancer Center, Sacramento, California 95817, United States
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center, Farmington, Connecticut 06360-2875, United States
Children's National Medical Center, Washington, District of Columbia 20010-2970, United States
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center, Washington, District of Columbia 20007, United States
All Children's Hospital, St. Petersburg, Florida 33701, United States
Kaplan Cancer Center at St. Mary's Medical Center, West Palm Beach, Florida 33407, United States
Memorial Cancer Institute at Memorial Regional Hospital, Hollywood, Florida 33021, United States
Nemours Children's Clinic - Orlando, Orlando, Florida 32806, United States
Nemours Children's Clinic, Jacksonville, Florida 32207, United States
Sacred Heart Cancer Center at Sacred Heart Hospital, Pensacola, Florida 32504, United States
St. Joseph's Cancer Institute at St. Joseph's Hospital, Tampa, Florida 33607, United States
University of Florida Shands Cancer Center, Gainesville, Florida 32610-0232, United States
Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center, Savannah, Georgia 31403-3089, United States
Winship Cancer Institute of Emory University, Atlanta, Georgia 30322, United States
Cancer Care Center at Advocate Lutheran Hospital, Park Ridge, Illinois 60068-1174, United States
Indiana University Cancer Center, Indianapolis, Indiana 46202-5289, United States
Blank Children's Hospital, Des Moines, Iowa 50309, United States
Kosair Children's Hospital, Louisville, Kentucky 40232, United States
Markey Cancer Center at University of Kentucky Chandler Medical Center, Lexington, Kentucky 40536-0293, United States
Children's Hospital of New Orleans, New Orleans, Louisiana 70118, United States
CancerCare of Maine at Eastern Maine Medial Center, Bangor, Maine 04401, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231-2410, United States
Barbara Ann Karmanos Cancer Institute, Detroit, Michigan 48201-1379, United States
Breslin Cancer Center at Ingham Regional Medical Center, Lansing, Michigan 48910, United States
C.S. Mott Children's Hospital at University of Michigan, Ann Arbor, Michigan 48109-0238, United States
CCOP - Kalamazoo, Kalamazoo, Michigan 49007-5341, United States
Hurley Medical Center, Flint, Michigan 48503, United States
Spectrum Health Hospital - Butterworth Campus, Grand Rapids, Michigan 49503-2560, United States
Van Elslander Cancer Center at St. John Hospital and Medical Center, Grosse Pointe Woods, Michigan 48236, United States
Children's Hospitals and Clinics of Minneapolis, Minneapolis, Minnesota 55404, United States
Mayo Clinic Cancer Center, Rochester, Minnesota 55905, United States
University of Minnesota Medical Center & Children's Hospital - Fairview, Minneapolis, Minnesota 55455, United States
University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, United States
Children's Mercy Hospital, Kansas City, Missouri 64108, United States
Siteman Cancer Center at Barnes-Jewish Hospital, St. Louis, Missouri 63110, United States
UNMC Eppley Cancer Center at the University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, United States
Sunrise Hospital and Medical Center, Las Vegas, Nevada 89109-2306, United States
Hackensack University Medical Center Cancer Center, Hackensack, New Jersey 07601, United States
Newark Beth Israel Medical Center, Newark, New Jersey 07112, United States
University of New Mexico Cancer Research and Treatment Center, Albuquerque, New Mexico 87131-5636, United States
Prince of Wales Private Hospital, Randwick, New South Wales 2031, Australia
Albert Einstein Cancer Center at Albert Einstein College of Medicine, Bronx, New York 10461, United States
James P. Wilmot Cancer Center at University of Rochester Medical Center, Rochester, New York 14642, United States
Mount Sinai Medical Center, New York, New York 10029, United States
New York Medical College, Valhalla, New York 10595, United States
Roswell Park Cancer Institute, Buffalo, New York 14263-0001, United States
Stony Brook University Cancer Center, Stony Brook, New York 11794-8174, United States
SUNY Upstate Medical University Hospital, Syracuse, New York 13210, United States
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill, Chapel Hill, North Carolina 27599-7295, United States
CCOP - MeritCare Hospital, Fargo, North Dakota 58122, United States
IWK Health Centre, Halifax, Nova Scotia B3K 6R8, Canada
Children's Hospital Medical Center of Akron, Akron, Ohio 44308-1062, United States
Children's Medical Center - Dayton, Dayton, Ohio 45404-1815, United States
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, United States
Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio 44195-5217, United States
Rainbow Babies and Children's Hospital, Cleveland, Ohio 44106-5000, United States
Toledo Hospital, Toledo, Ohio 43606, United States
Oklahoma University Medical Center, Oklahoma City, Oklahoma 73104, United States
Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada
Oregon Health & Science University Cancer Institute, Portland, Oregon 97239-3098, United States
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104-9786, United States
Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States
Penn State Cancer Institute at Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033-0850, United States
Hopital Sainte Justine, Montreal, Quebec H3T 1C5, Canada
Montreal Children's Hospital at McGill University Health Center, Montreal, Quebec H3H 1P3, Canada
Royal Children's Hospital, Herston, Brisbane, Queensland 4029, Australia
Saskatoon Cancer Centre at the University of Saskatchewan, Saskatoon, Saskatchewan S7N 4H4, Canada
Hollings Cancer Center at Medical University of South Carolina, Charleston, South Carolina 29425, United States
East Tennessee Children's Hospital, Knoxville, Tennessee 37916, United States
East Tennessee State University Cancer Center at Johnson City Medical Center, Johnson City, Tennessee 37604, United States
St. Jude Children's Research Hospital, Memphis, Tennessee 38105, United States
Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232-6310, United States
CCOP - Scott and White Hospital, Temple, Texas 76508, United States
Children's Hospital of Austin, Austin, Texas 78701, United States
Cook Children's Medical Center - Fort Worth, Fort Worth, Texas 76104-9958, United States
Covenant Children's Hospital, Lubbock, Texas 79410, United States
Methodist Children's Hospital of South Texas, San Antonio, Texas 78229-3993, United States
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas, Dallas, Texas 75390, United States
Texas Tech University Health Sciences Center School of Medicine - Amarillo, Amarillo, Texas 79106, United States
University of Texas Health Science Center at San Antonio, San Antonio, Texas 78207, United States
Fletcher Allen Health Care - University Health Center Campus, Burlington, Vermont 05405, United States
Children's Hospital of The King's Daughters, Norfolk, Virginia 23507-1971, United States
INOVA Fairfax Hospital, Fairfax, Virginia 22031, United States
Virginia Commonwealth University Massey Cancer Center, Richmond, Virginia 23298-0037, United States
Princess Margaret Hospital for Children, Perth, Western Australia 6001, Australia
Marshfield Clinic - Marshfield Center, Marshfield, Wisconsin 54449, United States
Midwest Children's Cancer Center, Milwaukee, Wisconsin 53226, United States
