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

Myelodysplastic Syndromes Clinical Trial

Official title:

A Phase II Study Of Amifostine In Children With Myelodysplastic Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00098683
• Other study ID #: AAML0121
• Secondary ID: CDR0000398140COG
• Status: Completed
• Phase: Phase 2
• First received: December 7, 2004
• Last updated: February 11, 2014
• Start date: January 2005
• Est. completion date: October 2009

Study information

• Verified date: February 2014
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: October 2009
• Est. primary completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 21 Years

Eligibility

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

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Neoplasms
• Myeloproliferative Disorders
• Preleukemia
• Syndrome

Intervention

Drug:
• amifostine trihydrate

Locations

Country	Name	City	State
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario
Canada	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario
Canada	Hopital Sainte Justine	Montreal	Quebec
Canada	Montreal Children's Hospital at McGill University Health Center	Montreal	Quebec
Canada	Centre Hospitalier Universitaire de Quebec	Quebec
Canada	Children's & Women's Hospital of British Columbia	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Puerto Rico	San Jorge Children's Hospital	Santurce
United States	Children's Hospital Medical Center of Akron	Akron	Ohio
United States	University of New Mexico Cancer Research and Treatment Center	Albuquerque	New Mexico
United States	Texas Tech University Health Sciences Center School of Medicine - Amarillo	Amarillo	Texas
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Children's Hospital of Austin	Austin	Texas
United States	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital	Baltimore	Maryland
United States	CancerCare of Maine at Eastern Maine Medial Center	Bangor	Maine
United States	Albert Einstein Cancer Center at Albert Einstein College of Medicine	Bronx	New York
United States	Maimonides Cancer Center at Maimonides Medical Center	Brooklyn	New York
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division	Charleston	West Virginia
United States	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	Columbus Children's Hospital	Columbus	Ohio
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Children's Medical Center - Dayton	Dayton	Ohio
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center	Farmington	Connecticut
United States	Hurley Medical Center	Flint	Michigan
United States	Lee Cancer Care of Lee Memorial Health System	Fort Myers	Florida
United States	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas
United States	University of Florida Shands Cancer Center	Gainesville	Florida
United States	Spectrum Health Hospital - Butterworth Campus	Grand Rapids	Michigan
United States	Greenville Hospital System Cancer Center	Greenville	South Carolina
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Hackensack University Medical Center Cancer Center	Hackensack	New Jersey
United States	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Memorial Cancer Institute at Memorial Regional Hospital	Hollywood	Florida
United States	Cancer Research Center of Hawaii	Honolulu	Hawaii
United States	Baylor University Medical Center - Houston	Houston	Texas
United States	Edwards Comprehensive Cancer Center at Cabell Huntington Hospital	Huntington	West Virginia
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	St. Vincent Indianapolis Hospital	Indianapolis	Indiana
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	East Tennessee Children's Hospital	Knoxville	Tennessee
United States	Breslin Cancer Center at Ingham Regional Medical Center	Lansing	Michigan
United States	Sunrise Hospital and Medical Center	Las Vegas	Nevada
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Jonathan Jaques Children's Cancer Center at Miller Children's Hospital	Long Beach	California
United States	Kosair Children's Hospital	Louisville	Kentucky
United States	Children's Hospital Central California	Madera	California
United States	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin
United States	Miami Children's Hospital	Miami	Florida
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	Overlook Hospital	Morristown	New Jersey
United States	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	Saint Peter's University Hospital	New Brunswick	New Jersey
United States	Ochsner Cancer Institute at Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Herbert Irving Comprehensive Cancer Center at Columbia University	New York	New York
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Oklahoma University Medical Center	Oklahoma City	Oklahoma
United States	UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Omaha	Nebraska
United States	Sacred Heart Cancer Center at Sacred Heart Hospital	Pensacola	Florida
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Kaiser Permanente Medical Center - Oakland	Sacramento	California
United States	Primary Children's Medical Center	Salt Lake City	Utah
United States	Methodist Children's Hospital of South Texas	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	Siteman Cancer Center at Barnes-Jewish Hospital	St. Louis	Missouri
United States	All Children's Hospital	St. Petersburg	Florida
United States	SUNY Upstate Medical University Hospital	Syracuse	New York
United States	St. Joseph's Cancer Institute at St. Joseph's Hospital	Tampa	Florida
United States	New York Medical College	Valhalla	New York
United States	Kaplan Cancer Center at St. Mary's Medical Center	West Palm Beach	Florida
United States	Tod Children's Hospital - Forum Health	Youngstown	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Puerto Rico, 

References & Publications (1)

Mathew P, Gerbing R, Alonzo TA, Wallas T, Gong JZ, Jasty R, Jorstad DT, Raimondi SC, Chavez CM, Eisenberg NL, Hirsch B, Gamis A, Smith FO, Arceci RJ. A phase II study of amifostine in children with myelodysplastic syndrome: a report from the Children's On — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hematological effects (complete and partial response)			No
Primary	Safety and efficacy			Yes
Secondary	Efficacy			No
Secondary	Duration of progression-free remission			No
Secondary	Effect of karyotypic abnormalities on survival			No
Secondary	Effect of the number of cytopenias on survival			No
Secondary	Correlation of the duration of time from diagnosis of myelodysplastic syndromes until conversion to acute myeloid leukemia			No