A Phase I Study of Cytosine Arabinoside, Idarubicin, and Amifostine as Induction Therapy for Patients With Newly Diagnosed Acute Myeloid Leukemia
18 Years
N/A
Both
Drug/Agent Toxicity by Tissue/Organ, Leukemia
Trial Information
A Phase I Study of Cytosine Arabinoside, Idarubicin, and Amifostine as Induction Therapy for Patients With Newly Diagnosed Acute Myeloid Leukemia
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Neal Flomenberg, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Kimmel Cancer Center (KCC)
Authority:
United States: Federal Government
Study ID:
CDR0000066164
NCT ID:
NCT00003268
Start Date:
January 1998
Completion Date:
Related Keywords:
- Drug/Agent Toxicity by Tissue/Organ
- Leukemia
- untreated adult acute myeloid leukemia
- adult acute monoblastic leukemia and acute monocytic leukemia (M5)
- adult acute erythroid leukemia (M6)
- adult acute myeloblastic leukemia without maturation (M1)
- adult acute myeloblastic leukemia with maturation (M2)
- adult acute myelomonocytic leukemia (M4)
- adult acute megakaryoblastic leukemia (M7)
- drug/agent toxicity by tissue/organ
- adult acute minimally differentiated myeloid leukemia (M0)
- Leukemia
- Leukemia, Myeloid, Acute
- Leukemia, Myeloid
Name | Location |
|---|---|
| Kimmel Cancer Center of Thomas Jefferson University - Philadelphia | Philadelphia, Pennsylvania 19107 |
