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

NCT00083187 | Completed Phase 2

• 2 other identifiers: VION-CLI-033CDR0000365510
• Study Type: interventional
• Target: 230
• Locations: 3 countries
• Sites: 5

Brief Summary

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.

Conditions

Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms

Keywords

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)

Outcome Measures

Primary Outcomes (3)

• Complete response rate

• Toxic effects

• Pharmacokinetics

Interventions

hydroxyurea DRUG

laromustine DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Vion Pharmaceuticals: lead

Study Sites (5)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

M.D. Anderson Cancer Center at University of Texas

Houston, Texas, 77030-4009, United States

Location

Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes

Marseille, 13273, France

Location

King's College Hospital

London, England, SE5 8RX, United Kingdom

Location

Related Publications (2)

• Gerson SL, Karp J, Rizzieri D, et al.: Low levels of pre-treatment O6-alkylguanine transferase (AGT) in patients with AML correlate with response to Cloretazine® (VNP40101M) induction therapy. [Abstract] American Association for Cancer Research: 98th Annual Meeting, April 14-18, 2007, Los Angeles, CA. A-2640, 2007.

  RESULT

• Giles F, Rizzieri D, Karp J, Vey N, Ravandi F, Faderl S, Khan KD, Verhoef G, Wijermans P, Advani A, Roboz G, Kantarjian H, Bilgrami SF, Ferrant A, Daenen SM, Karsten V, Cahill A, Albitar M, Mufti G, O'Brien S. Cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, in patients age 60 years or older with previously untreated acute myeloid leukemia. J Clin Oncol. 2007 Jan 1;25(1):25-31. doi: 10.1200/JCO.2006.07.0961. Epub 2006 Dec 4.

  PMID: 17146105 RESULT

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Myeloid, Acute; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Leukemia, Myelomonocytic, Chronic; Myeloproliferative Disorders; Congenital Abnormalities

Interventions

Hydroxyurea; laromustine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, Myeloid; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals

Study Officials

• Francis J. Giles, MD

  M.D. Anderson Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: May 14, 2004
• First Posted: May 17, 2004
• Study Start: November 1, 2005
• Primary Completion: January 1, 2007
• Study Completion: August 1, 2008
• Last Updated: July 18, 2013

Record last verified: 2008-08

Locations

US (3); GB (1); FR (1)