Clinical trial NCT00098683: Amifostine 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms
Keywords: refractory anemia with excess blasts
refractory anemia
refractory anemia with ringed sideroblasts
de novo myelodysplastic syndromes
myelodysplastic/myeloproliferative neoplasm, unclassifiable
refractory cytopenia with multilineage dysplasia
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-12-08
Enrollment: 10
Sex: ALL
Minimum age (years): 1
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility 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

Primary outcomes:
measure: Hematological effects (complete and partial response)
measure: Safety and efficacy
Secondary outcomes:
measure: Efficacy
measure: Duration of progression-free remission
measure: Effect of karyotypic abnormalities on survival
measure: Effect of the number of cytopenias on survival
measure: Correlation of the duration of time from diagnosis of myelodysplastic syndromes until conversion to acute myeloid leukemia
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
state: Arkansas
city: Long Beach
country: United States
facility: Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
state: California
city: Madera
country: United States
facility: Children's Hospital Central California
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente Medical Center - Oakland
state: California
city: Farmington
country: United States
facility: Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
state: Connecticut
city: Fort Myers
country: United States
facility: Lee Cancer Care of Lee Memorial Health System
state: Florida
city: Gainesville
country: United States
facility: University of Florida Shands Cancer Center
state: Florida
city: Hollywood
country: United States
facility: Memorial Cancer Institute at Memorial Regional Hospital
state: Florida
city: Miami
country: United States
facility: Miami Children's Hospital
state: Florida
city: Pensacola
country: United States
facility: Sacred Heart Cancer Center at Sacred Heart Hospital
state: Florida
city: St. Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: Tampa
country: United States
facility: St. Joseph's Cancer Institute at St. Joseph's Hospital
state: Florida
city: West Palm Beach
country: United States
facility: Kaplan Cancer Center at St. Mary's Medical Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Honolulu
country: United States
facility: Cancer Research Center of Hawaii
state: Hawaii
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: St. Vincent Indianapolis Hospital
state: Indiana
city: Kansas City
country: United States
facility: Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
state: Kansas
city: Louisville
country: United States
facility: Kosair Children's Hospital
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Cancer Institute at Ochsner Clinic Foundation
state: Louisiana
city: Bangor
country: United States
facility: CancerCare of Maine at Eastern Maine Medial Center
state: Maine
city: Baltimore
country: United States
facility: Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
state: Maryland
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health Hospital - Butterworth Campus
state: Michigan
city: Grosse Pointe Woods
country: United States
facility: Van Elslander Cancer Center at St. John Hospital and Medical Center
state: Michigan
city: Lansing
country: United States
facility: Breslin Cancer Center at Ingham Regional Medical Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: St. Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital
state: Missouri
city: Omaha
country: United States
facility: UNMC Eppley Cancer Center at the University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: Sunrise Hospital and Medical Center
state: Nevada
city: Hackensack
country: United States
facility: Hackensack University Medical Center Cancer Center
state: New Jersey
city: Morristown
country: United States
facility: Overlook Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Saint Peter's University Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Research and Treatment Center
state: New Mexico
city: Bronx
country: United States
facility: Albert Einstein Cancer Center at Albert Einstein College of Medicine
state: New York
city: Brooklyn
country: United States
facility: Maimonides Cancer Center at Maimonides Medical Center
state: New York
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center at Columbia University
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Hospital
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Blumenthal Cancer Center at Carolinas Medical Center
state: North Carolina
city: Akron
country: United States
facility: Children's Hospital Medical Center of Akron
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: Columbus Children's Hospital
state: Ohio
city: Dayton
country: United States
facility: Children's Medical Center - Dayton
state: Ohio
city: Youngstown
country: United States
facility: Tod Children's Hospital - Forum Health
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Medical Center
state: Oklahoma
city: Hershey
country: United States
facility: Penn State Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: St. Christopher's Hospital for Children
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: Hollings Cancer Center at Medical University of South Carolina
state: South Carolina
city: Greenville
country: United States
facility: Greenville Hospital System Cancer Center
state: South Carolina
city: Knoxville
country: United States
facility: East Tennessee Children's Hospital
state: Tennessee
city: Amarillo
country: United States
facility: Texas Tech University Health Sciences Center School of Medicine - Amarillo
state: Texas
city: Austin
country: United States
facility: Children's Hospital of Austin
state: Texas
city: Dallas
country: United States
facility: Medical City Dallas Hospital
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center - Fort Worth
state: Texas
city: Houston
country: United States
facility: Baylor University Medical Center - Houston
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: San Antonio
country: United States
facility: Methodist Children's Hospital of South Texas
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Medical Center
state: Utah
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center - Seattle
state: Washington
city: Charleston
country: United States
facility: West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division
state: West Virginia
city: Huntington
country: United States
facility: Edwards Comprehensive Cancer Center at Cabell Huntington Hospital
state: West Virginia
city: Marshfield
country: United States
facility: Marshfield Clinic - Marshfield Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Midwest Children's Cancer Center
state: Wisconsin
city: Perth
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Vancouver
country: Canada
facility: Children's & Women's Hospital of British Columbia
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Halifax
country: Canada
facility: IWK Health Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster Children's Hospital at Hamilton Health Sciences
state: Ontario
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario at Kingston General Hospital
state: Ontario
city: Montreal
country: Canada
facility: Montreal Children's Hospital at McGill University Health Center
state: Quebec
city: Montreal
country: Canada
facility: Hopital Sainte Justine
state: Quebec
city: Quebec
country: Canada
facility: Centre Hospitalier Universitaire de Quebec
city: Santurce
country: Puerto Rico
facility: San Jorge Children's Hospital
Study officials:
affiliation: University of New Mexico Cancer Center
name: Prasad Mathew, MD
role: STUDY_CHAIR
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Robert J. Arceci, MD, PhD
References:
citation: 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 Oncology Group study (AAML0121). Pediatr Blood Cancer. 2011 Dec 15;57(7):1230-2. doi: 10.1002/pbc.23164. Epub 2011 Jun 16.