Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Objectives

Primary

1. Determine the hematologic effects of amifostine, in terms of, complete and partial response, in pediatric patients with newly diagnosed de novo myelodysplastic syndromes (MDS).
2. Determine the safety and efficacy of this drug in these patients.

Secondary

1. 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.
2. Determine the duration of progression-free remission from MDS conversion to AML in patients treated with this drug.
3. 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.
4. 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.
5. Determine the effect of the number of cytopenias on survival in patients treated with this drug.
6. Correlate the duration of time from diagnosis of MDS until conversion to AML with survival in patients treated with this drug.

Entry 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

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

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

Expected Enrollment

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

Outcomes

Hematological effects (complete and partial response)
Safety and efficacy

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

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.

Mathew P, Gerbing R, Alonzo TA, et al.: A phase II study of amifostine in children with myelodysplastic syndrome: a report from the Children's Oncology Group study (AAML0121). Pediatr Blood Cancer 57 (7): 1230-2, 2011.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Prasad Mathew, MD, Protocol chair		Ph: 505-272-4461
Robert Arceci, MD, PhD, Protocol co-chair		Ph: 410-502-7519 Email: arcecro@jhmi.edu

Registry Information
Official Title		A Phase II Study Of Amifostine In Children With Myelodysplastic Syndrome
Trial Start Date		2005-01-31
Trial Completion Date		2007-10-01
Registered in ClinicalTrials.gov		NCT00098683
Date Submitted to PDQ		2004-10-13
Information Last Verified		2010-11-12
NCI Grant/Contract Number		CA98543

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