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

Children's Oncology Group

Status and phase: Completed; Phase 2

Conditions: Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms

Treatments: Drug: amifostine trihydrate

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00098683

CDR0000398140 (Other Identifier)

COG-AAML0121 (Other Identifier)

AAML0121

Details and patient eligibility

About

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.

Full 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.

Enrollment: 10 patients

Sex: All

Ages: 1 to 21 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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