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: Phase II trial to study the effectiveness of combining VNP40101M with hydroxyurea in treating patients who have acute myelogenous leukemia or high-risk myelodysplasia.

Condition	Treatment or Intervention	Phase
adult acute myeloid leukemia atypical chronic myeloid leukemia Chronic Myelomonocytic Leukemia myelodysplastic and myeloproliferative disease Myelodysplastic Syndromes	Drug: VNP40101M  Drug: hydroxyurea  Procedure: chemosensitization/potentiation  Procedure: chemotherapy	Phase II

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.

OUTLINE: This is an open-label, multicenter study.

Patients receive VNP40101M IV over 30 minutes once on day 1 and oral hydroxyurea every 12 hours on days 1-3 for a total of 6 doses (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) and hydroxyurea (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 in combination with hydroxyurea at the same dose as in course 1.

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 76-230 patients (33-100 with acute myelogenous leukemia (AML) or high-risk myelodysplasia and 43-130 with AML in first relapse) will be accrued for this study within 12-18 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of 1 of the following:
• Acute myelogenous leukemia
• Less than 60 years of age and meeting the following criteria:
• In first relapse after first treatment-induced complete remission (CR)
• Duration of first CR less than 12 months
• No prior treatment for first relapse except hydroxyurea
• 60 years of age and over and meeting 1 of the following criteria:
• In first relapse after first treatment-induced CR
• No prior treatment for first relapse except hydroxyurea
• Prior low-dose, single-agent cytarabine, decitabine, or azacitidine not considered prior cytotoxic chemotherapy
• Duration of first CR < 12 months
• No prior treatment with a standard induction regimen containing cytotoxic agents
• High-risk myelodysplasia, meeting the following criteria:
• 60 years of age and over
• No prior cytotoxic chemotherapy except hydroxyurea
• Prior low-dose, single-agent cytarabine, decitabine, or azacitidine not considered prior cytotoxic chemotherapy
• High risk defined as International Prognostic Scoring System score ≥ 1.5, defined by cytogenetics, % marrow blasts, and lineage cytopenias

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

Connecticut
      Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center, Hartford,  Connecticut,  06105,  United States; Recruiting
Indiana
      Indiana Oncology Hematology Consultants, Indianapolis,  Indiana,  46202,  United States; Recruiting
New York
      New York Weill Cornell Cancer Center at Cornell University, New York,  New York,  10021,  United States; Recruiting
North Carolina
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States; Recruiting
Texas
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030-4095,  United States; Recruiting
Belgium
      Cliniques Universitaires Saint-Luc, Brussels,  1200,  Belgium; Recruiting
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium; Recruiting
United Kingdom, England
      King's College Hospital, London,  England,  SE5 8RX,  United Kingdom; Recruiting

Study chairs or principal investigators

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

Study ID Numbers:  CDR0000365510; VION-CLI-033
Record last reviewed:  July 2004
Record first received:  May 14, 2004
ClinicalTrials.gov Identifier:  NCT00083187
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-18