6-Hydroxymethylacylfulvene in Treating Patients With Refractory Myelodysplastic Syndrome, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, or Blastic Phase Chronic Myelogenous Leukemia

Study Overview
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Brief Summary
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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. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

Detailed Description
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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. 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.

Official Title
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Phase I Study of MGI-114 (NSC#683863) in Patients With Refractory Myelodysplastic Syndromes, Acute Leukemia and Chronic Myelogenous Leukemia in Blastic Phase (CML-BP)

Conditions
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Leukemia, Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: irofulven


Participation Criteria
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Eligibility Criteria
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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 PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Zubrod 0-2 Bilirubin no greater than 1.5 mg/dL Creatinine no greater than 1.5 mg/dL OR creatinine clearance at least 60 mL/min No active congestive heart failure No uncontrolled angina No myocardial infarction within past 6 months 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 PRIOR CONCURRENT THERAPY: At least 2 weeks since prior biologic therapy and recovered No concurrent systemic anticancer biologic therapy At least 2 weeks since other prior chemotherapy and recovered Concurrent hydroxyurea allowed if needed to control blast counts No concurrent systemic anticancer chemotherapy At least 2 weeks since prior endocrine therapy and recovered Concurrent corticosteroids allowed if needed to control blast counts At least 2 weeks since prior radiotherapy and recovered No concurrent systemic radiotherapy No concurrent surgery At least 3 weeks since other prior investigational drugs (including analgesics or antiemetics) and recovered No other concurrent investigational drugs

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>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. | Drug: irofulven<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult acute myeloid leukemia, recurrent adult acute lymphoblastic leukemia, blastic phase chronic myelogenous leukemia, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes