RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. PURPOSE: Phase I trial to study the effectiveness of 6-hydroxymethylacylfulvene in treating patients who have refractory myelodysplastic syndrome, acute myeloid leukemia, acute lymphocytic leukemia, or blastic phase chronic myelogenous leukemia.

Condition	Treatment or Intervention	Phase
Previously Treated Myelodysplastic Syndrome secondary myelodysplastic syndrome recurrent adult acute myeloid leukemia recurrent adult acute lymphocytic leukemia blastic phase chronic myelogenous leukemia	Drug: -hydroxymethylacylfulvene	Phase I

OBJECTIVES: I. Determine the maximum tolerated dose for 6-hydroxymethylacylfulvene in patients with refractory myelodysplastic syndrome, acute myeloid leukemia, acute lymphocytic leukemia, or blastic phase chronic myelogenous leukemia. II. Determine the qualitative and quantitative toxicities of this treatment in these patients. III. Determine the duration and reversibility of the qualitative and quantitative toxicities of this treatment in these patients. IV. Evaluate, in a preliminary manner, the antileukemic activity of this treatment in these patients. V. Assess relative mRNA levels of selected NER genes (ERCC1, ERCC2, and ERCC3) in tumor tissues of patients treated with this regimen and correlate with clinical outcome.

PROTOCOL OUTLINE: This is a dose escalation study. Patients receive 6-hydroxymethylacylfulvene (HMAF) IV over 5 minutes on days 1-5. Treatment repeats every 3-4 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3 patients receive escalating doses of HMAF. The maximum tolerated dose is defined as the dose at which dose limiting toxicity occurs in at least 40% of patients. Patients are followed every 3 months for 1 year and then every 6 months thereafter.

PROJECTED ACCRUAL: Approximately 25 patients will be accrued for this study at a rate of 2-4 patients per month.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Diagnosis of refractory myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), acute lymphocytic leukemia, or blastic phase chronic myelogenous leukemia
• MDS and AML include: First salvage with primary refractory disease or first complete remission of no more than 12 months Second or greater salvage
• After the maximum tolerated dose is determined, AML patients with an intermediate prognosis (i.e., complete remission of more than 12 months, but less than 24 months) are eligible
• No candidates for curative therapies such as allogeneic bone marrow transplantation

--Prior/Concurrent Therapy--

• Biologic therapy: At least 2 weeks since prior biologic therapy and recovered No concurrent systemic anticancer biologic therapy
• Chemotherapy: At least 2 weeks since other prior chemotherapy and recovered; Concurrent hydroxyurea allowed if needed to control blast counts; No concurrent systemic anticancer chemotherapy
• Endocrine therapy: At least 2 weeks since prior endocrine therapy and recovered; Concurrent corticosteroids allowed if needed to control blast counts
• Radiotherapy: At least 2 weeks since prior radiotherapy and recovered; No concurrent systemic radiotherapy
• Surgery: No concurrent surgery
• Other: At least 3 weeks since other prior investigational drugs (including analgesics or antiemetics) and recovered; No other concurrent investigational drugs

--Patient Characteristics--

• Age: 18 and over
• Performance status: Zubrod 0-2
• Life expectancy: Not specified
• Hematopoietic: Not specified
• Hepatic: Bilirubin no greater than 1.5 mg/dL
• Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance at least 60 mL/min
• Cardiovascular: No active congestive heart failure; No uncontrolled angina; No myocardial infarction within past 6 months
• Other: No concurrent grade 4 infection; Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception; No overt psychosis, mental disability, or other incompetency that would preclude obtaining informed consent; No life threatening nonmalignant illness

Texas
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030,  United States

Study chairs or principal investigators

Francis J. Giles,  Study Chair,  M.D. Anderson Cancer Center   

Study ID Numbers:  CDR0000067207; MDA-ID-99060; NCI-T99-0043
Record last reviewed:  June 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003997
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-10-14