VNP40101M in Treating Patients With Acute Myelogenous Leukemia or High-Risk Myelodysplasia

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as VNP40101M and hydroxyurea, work in different ways to stop cancer cells from dividing so they stop growing or die. Hydroxyurea may help VNP40101M kill more cancer cells by making cancer cells more sensitive to the drug. PURPOSE: This phase II trial is studying how well giving VNP40101M with hydroxyurea works in treating patients with acute myelogenous leukemia or high-risk myelodysplasia.

Detailed Description
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OBJECTIVES: Determine the complete response rate to VNP40101M in patients with acute myelogenous leukemia or high-risk myelodysplasia . Determine the toxic effects of this regimen in these patients. Determine the pharmacokinetics of this regimen in these patients. OUTLINE: This is an open-label, multicenter study. Patients are stratified to acute myelogenous leukemia (AML) or high risk myelodysplasia (MDS) patients ≥ 60 years old with no prior treatment vs AML patients any age in first relapse. (AML patients any age in first relapse closed to accrual 06/09/05). Patients receive VNP40101M IV over 30 minutes once on day 1 (course 1). Four to five weeks after the first course, patients undergo bone marrow aspiration and biopsy. If the bone marrow is improved but contains residual leukemia, patients receive a second course of VNP40101M (at the same dose as in course 1). If patients achieve complete response (CR), or partial CR after the first or second course, a consolidation course may be given comprising VNP40101M at a reduced dose. Patients are followed monthly for 6 months, every 2 months for 12 months, and then every 3 months for 18 months . PROJECTED ACCRUAL: A total of 230 patients (100 with acute myelogenous leukemia (AML) or high-risk myelodysplasia and 130 with AML in first relapse) will be accrued for this study.

Official Title
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A Phase II Study of VNP40101M For Patients With Acute Myelogenous Leukemia Or High-Risk Myelodysplasia

Conditions
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Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms

Intervention / Treatment
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* Drug: hydroxyurea
* Drug: laromustine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed diagnosis of 1 of the following: Acute myelogenous leukemia (AML), meeting the following criteria: In first relapse after first treatment-induced complete remission (CR) (closed to accrual as of 06/09/05) Duration of first CR less than 12 months No prior treatment for first relapse except hydroxyurea FAB type M0, M1, M2, M4-7 No acute promyelocytic leukemia No prior treatment with a standard induction regimen containing cytotoxic agents* (for patients 60 years of age or older) High-risk myelodysplasia, meeting the following criteria: 60 years of age and over No prior cytotoxic chemotherapy* except hydroxyurea Prior gemtuzumab ozogamicin allowed High risk defined as International Prognostic Scoring System score ≥ 1.5, defined by cytogenetics, % marrow blasts, and lineage cytopenias NOTE: *Prior low-dose, single-agent cytarabine, decitabine, or azacitidine not considered prior cytotoxic chemotherapy PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic Not specified Hepatic Bilirubin ≤ 2.0 mg/dL ALT or AST ≤ 5 times upper limit of normal Chronic hepatitis allowed Renal Creatinine ≤ 2.0 mg/dL Cardiovascular No myocardial infarction within the past 3 months No symptomatic coronary artery disease No uncontrolled arrhythmias No uncontrolled congestive heart failure No other active heart disease Other No uncontrolled active infection Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy Up to 4 leukapheresis procedures allowed during the first 15 days of study treatment Chemotherapy See Disease Characteristics Concurrent additional hydroxyurea (maximum dose of 5 g daily for up to 4 days) allowed between days 4 and 15 of each study course to control elevated blast levels Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified Other Recovered from all prior therapy At least 72 hours since prior anti-leukemic treatment with a non-cytotoxic agent No concurrent disulfiram (Antabuse) No other concurrent anticancer drugs except anagrelide within the first 15 days of study treatment to control elevated platelet counts No other concurrent treatment for leukemia, except hydroxyurea used during study treatment 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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: hydroxyurea|nan|
|Drug: laromustine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate |  |  | 
| Toxic effects |  |  | 
| Pharmacokinetics |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult acute myeloid leukemia, untreated adult acute myeloid leukemia, atypical chronic myeloid leukemia, BCR-ABL1 negative, chronic myelomonocytic leukemia, myelodysplastic/myeloproliferative neoplasm, unclassifiable, secondary myelodysplastic syndromes, de novo myelodysplastic syndromes, adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with t(15;17)(q22;q12)