Amifostine in Treating Young Patients With Newly Diagnosed De Novo Myelodysplastic Syndromes

Condition(s) targeted: Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases

Intervention: amifostine trihydrate (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Children's Oncology Group

Official(s) and/or principal investigator(s):
Prasad Mathew, MD, Study Chair, Affiliation: University of New Mexico
Robert J. Arceci, MD, PhD, Affiliation: Sidney Kimmel Comprehensive Cancer Center

RATIONALE: Drugs used in chemotherapy, such as amifostine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase II trial is studying how well amifostine works in treating young patients with newly diagnosed de novo myelodysplastic syndromes.

Official title: A Phase II Study Of Amifostine In Children With Myelodysplastic Syndrome

Study design: Treatment, Open Label

Primary outcome:

Hematological effects (complete and partial response)

Safety and efficacy

Secondary outcome:

Efficacy

Duration of progression-free remission

Effect of karyotypic abnormalities on survival

Effect of the number of cytopenias on survival

Correlation of the duration of time from diagnosis of myelodysplastic syndromes until conversion to acute myeloid leukemia

Detailed description: OBJECTIVES:

Primary

- Determine the hematologic effects of amifostine, in terms of, complete and partial

response, in pediatric patients with newly diagnosed de novo myelodysplastic syndromes (MDS).

- Determine the safety and efficacy of this drug in these patients.

Secondary

- Determine the efficacy of this drug in preventing conversion of MDS to acute myeloid

leukemia (AML) in terms of the proportion of patients who remain free of AML at the completion of study treatment.

- Determine the duration of progression-free remission from MDS conversion to AML in

patients treated with this drug.

- Determine the effect of karyotypic abnormalities on survival and the duration from

diagnosis of MDS until conversion to AML in patients treated with this drug.

- Determine the effect of bone marrow blast count on survival and the duration from

diagnosis of MDS until conversion to AML in patients treated with this drug.

- Determine the effect of the number of cytopenias on survival in patients treated with

this drug.

- Correlate the duration of time from diagnosis of MDS until conversion to AML with

survival in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive amifostine IV over 1-3 minutes on days 1, 3, 5, 8, 10, 12, 15, 17, and 19. Treatment repeats every 5 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease who are planning to undergo matched donor bone marrow or cord blood transplantation continue therapy until transplantation. Patients with stable or responding disease who are not undergoing transplantation may receive up to 4 additional courses of amifostine in the absence of disease progression or unacceptable toxicity.

Following completion of therapy with amifostine, patients are followed monthly for 1 year, every 2 months for 1 year, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 10-20 patients will be accrued for this study within 5-10 months.

Minimum age: 1 Year. Maximum age: 21 Years. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS:

- Histologically confirmed diagnosis of myelodysplastic syndromes (MDS)

- One of the following subtypes:

- Refractory anemia (RA)

- RA with ringed sideroblasts

- RA with excess blasts

- Refractory cytopenia with multilineage dysplasia (RCMD)

- RCMD and ringed sideroblasts

- MDS, unclassified

- MDS associated with isolated del 5(q)

- De novo disease

- No treatment-induced MDS

- No juvenile myelomonocytic leukemia

- No Down syndrome, Fanconi's anemia, or other inherited forms of hypoplastic bone

marrow failure

PATIENT CHARACTERISTICS:

Age

- 1 to 21 at original diagnosis

Performance status

- Karnofsky 50-100% (patients > 16 years of age)

- Lansky 50-100% (patients 1 to 16 years of age)

Life expectancy

- At least 8 weeks

Hematopoietic

- See Disease Characteristics

Hepatic

- Bilirubin ≤ 1. 5 times upper limit of normal (ULN)

- ALT < 2. 5 times ULN

Renal

- Radioisotope glomerular filtration rate ≥ 60 mL/min OR

- Creatinine clearance > 60 mL/min (based on Schwartz formula)

- Calcium normal

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Serum electrolytes normal

- Phosphorus normal

- Magnesium normal

- Glucose normal

- No other concurrent malignancy

PRIOR CONCURRENT THERAPY:

Biologic therapy

- More than 8 weeks since prior growth factors

- No concurrent growth factors

- No concurrent hematopoietic stem cell transplantation

- No concurrent immunomodulating agents

Chemotherapy

- No prior amifostine

- No other concurrent anticancer chemotherapy

Endocrine therapy

- No concurrent daily steroid therapy

Radiotherapy

- Not specified

Surgery

- Not specified

Other

- No prior therapy for MDS

Centre Hospitalier Universitaire de Quebec, Quebec G1V 4G2, Canada

San Jorge Children's Hospital, Santurce 00912, Puerto Rico

University of Alberta Hospital, Edmonton, Alberta T6G 1Z2, Canada

Phoenix Children's Hospital, Phoenix, Arizona 85016-7710, United States

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, United States

Children's & Women's Hospital of British Columbia, Vancouver, British Columbia V6H 3V4, Canada

Children's Hospital Central California, Madera, California 93638-8762, United States

Jonathan Jaques Children's Cancer Center at Miller Children's Hospital, Long Beach, California 90801, United States

Kaiser Permanente Medical Center - Oakland, Sacramento, California 95825, United States

Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center, Farmington, Connecticut 06360-2875, 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

Lee Cancer Care of Lee Memorial Health System, Fort Myers, Florida 33901, United States

Memorial Cancer Institute at Memorial Regional Hospital, Hollywood, Florida 33021, United States

Miami Children's Hospital, Miami, Florida 33155, 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

Winship Cancer Institute of Emory University, Atlanta, Georgia 30322, United States

Cancer Research Center of Hawaii, Honolulu, Hawaii 95813, United States

Advocate Christ Medical Center, Oak Lawn, Illinois 60453, United States

Indiana University Cancer Center, Indianapolis, Indiana 46202-5289, United States

St. Vincent Indianapolis Hospital, Indianapolis, Indiana 46260, United States

Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center, Kansas City, Kansas 66160-7357, United States

Kosair Children's Hospital, Louisville, Kentucky 40232, United States

Ochsner Cancer Institute at Ochsner Clinic Foundation, New Orleans, Louisiana 70121, United States

CancerCare of Maine at Eastern Maine Medial Center, Bangor, Maine 04401, United States

CancerCare Manitoba, Winnipeg, Manitoba R3E 0V9, Canada

Alvin and Lois Lapidus Cancer Institute at Sinai Hospital, Baltimore, Maryland 21215, 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

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

Mayo Clinic Cancer Center, Rochester, Minnesota 55905, 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

Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903, United States

Hackensack University Medical Center Cancer Center, Hackensack, New Jersey 07601, United States

Overlook Hospital, Morristown, New Jersey 07962, United States

Saint Peter's University Hospital, New Brunswick, New Jersey 08901, United States

University of New Mexico Cancer Research and Treatment Center, Albuquerque, New Mexico 87131-5636, United States

Albert Einstein Cancer Center at Albert Einstein College of Medicine, Bronx, New York 10461, United States

Herbert Irving Comprehensive Cancer Center at Columbia University, New York, New York 10032, United States

Maimonides Cancer Center at Maimonides Medical Center, Brooklyn, New York 11219, United States

New York Medical College, Valhalla, New York 10595, United States

SUNY Upstate Medical University Hospital, Syracuse, New York 13210, United States

Blumenthal Cancer Center at Carolinas Medical Center, Charlotte, North Carolina 28232-2861, United States

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill, Chapel Hill, North Carolina 27599-7295, 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

Columbus Children's Hospital, Columbus, Ohio 43205-2696, United States

Rainbow Babies and Children's Hospital, Cleveland, Ohio 44106-5000, United States

Tod Children's Hospital - Forum Health, Youngstown, Ohio 44501, United States

Oklahoma University Medical Center, Oklahoma City, Oklahoma 73104, United States

Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, Ontario K7L 3N6, Canada

McMaster Children's Hospital at Hamilton Health Sciences, Hamilton, Ontario L8N 3Z5, Canada

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

St. Christopher's Hospital for Children, Philadelphia, Pennsylvania 19134-1095, United States

Hopital Sainte Justine, Montreal, Quebec H3T 1C5, Canada

Montreal Children's Hospital at McGill University Health Center, Montreal, Quebec H3H 1P3, Canada

Greenville Hospital System Cancer Center, Greenville, South Carolina 29605, United States

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

Baylor University Medical Center - Houston, Houston, Texas 77030-2399, 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

Medical City Dallas Hospital, Dallas, Texas 75230, United States

Methodist Children's Hospital of South Texas, San Antonio, Texas 78229-3993, 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

Primary Children's Medical Center, Salt Lake City, Utah 84113-1100, United States

Children's Hospital and Regional Medical Center - Seattle, Seattle, Washington 98105, United States

Edwards Comprehensive Cancer Center at Cabell Huntington Hospital, Huntington, West Virginia 25701, United States

West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division, Charleston, West Virginia 25302, 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

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: January 2005
Last updated: May 23, 2008