RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Chemoprotective drugs, such as amifostine, may protect normal cells from the side effects of chemotherapy.

PURPOSE: Phase I trial to study the effectiveness of amifostine in treating patients with newly diagnosed acute myeloid leukemia who are receiving idarubicin plus cytarabine.

Condition	Treatment or Intervention	Phase
adult acute myeloid leukemia Drug Toxicity	Drug: amifostine  Drug: cytarabine  Drug: idarubicin  Procedure: cardiotoxicity attenuation  Procedure: chemoprotection  Procedure: chemotherapy  Procedure: neurotoxicity attenuation  Procedure: supportive care/therapy	Phase I

Further Study Details: 

OBJECTIVES:

• Determine whether amifostine provides systemic protection against the nonhematologic side effects of idarubicin (IDR) during induction therapy of acute myeloid leukemia (AML), allowing the dose of idarubicin to be escalated.
• Determine the maximum tolerated dose of idarubicin when amifostine is used as a chemotherapy protectant.
• Determine the incidence and severity of dose limiting hypotension in patients receiving amifostine and the ability to offset this side effect with vasoconstrictive agents.
• Determine whether any additional side effects of amifostine are dose limiting in patients with AML treated with IDR and cytarabine (ARA-C).
• Monitor the frequency of alopecia, mucositis, diarrhea, and septicemia involving enteric pathogens in these patients.
• Determine the requirement for intravenous hyperalimentation in patients receiving amifostine, IDR, and ARA-C.

OUTLINE: This is a dose escalation study of idarubicin (IDR).

Patients receive amifostine IV over 15 minutes, followed 15-30 minutes later by chemotherapy. Idarubicin IV is administered over 15 minutes on days 1-3. Cytarabine is administered by continuous infusion on days 1-7. Patients may receive 1 additional course of treatment, if necessary.

Cohorts of 3-6 patients each are treated at each dose level of idarubicin. Dose escalation is discontinued when 2 or more patients experience dose limiting toxicity.

Patients are followed at 3 months.

PROJECTED ACCRUAL: A maximum of 36 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Newly diagnosed acute myeloid leukemia (AML)
• M0-M2, M4-M7
• Histologically proven by bone marrow aspirate and biopsy (requirement may be waived for patients with overt leukemia in the peripheral blood)
• M3 (acute promyelocytic leukemia) patients excluded unless already treated with trans retinoic acid
• Evaluable disease

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• Karnofsky 60-100%
• ECOG 0-2

Life expectancy:

• At least 3 months

Hematopoietic:

• Not specified

Hepatic:

• SGOT/SGPT no greater than 2.5 times upper limit of normal

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• Ejection fraction at least 50%
• Must be able to stop taking antihypertensive medication 24 hours prior to cytarabine administration

Other:

• No preexisting severe organ dysfunction
• No history of underlying medical or psychiatric illness that may impair the patient's ability to participate in the study
• Not pregnant or nursing
• Effective contraception required of fertile patients

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• No prior cytotoxic therapy for AML
• No prior amifostine
• At least 1 month since chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 1 month since radiotherapy

Surgery:

• Not specified

Pennsylvania
      Kimmel Cancer Center of Thomas Jefferson University - Philadelphia, Philadelphia,  Pennsylvania,  19107-5541,  United States

Study chairs or principal investigators

Neal Flomenberg, MD,  Study Chair,  Kimmel Cancer Center (KCC)   

Study ID Numbers:  CDR0000066164; TJUH-980407; ALZA-97-040-ii; NCI-V98-1395
Record last reviewed:  December 2003
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003268
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08