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

Sponsored by:	Vion Pharmaceuticals
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00083187

Purpose

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.

Condition	Intervention	Phase
Leukemia Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases	Drug: hydroxyurea Drug: laromustine	Phase II

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Hydroxyurea Cloretazine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase II Study of VNP40101M For Patients With Acute Myelogenous Leukemia Or High-Risk Myelodysplasia

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Complete response rate [ Designated as safety issue: No ]
Toxic effects [ Designated as safety issue: Yes ]
Pharmacokinetics [ Designated as safety issue: No ]

Estimated Enrollment:	230
Study Start Date:	November 2005
Primary Completion Date:	January 2007 (Final data collection date for primary outcome measure)

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00083187

Locations

United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Texas
M.D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
France
Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
Marseille, France, 13273
United Kingdom, England
King's College Hospital
London, England, United Kingdom, SE5 8RX

Sponsors and Collaborators

Vion Pharmaceuticals

Investigators

Study Chair:

Francis J. Giles, MD

M.D. Anderson Cancer Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications of Results:

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.

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. Epub 2006 Dec 4.

Study ID Numbers:	CDR0000365510, VION-CLI-033
Study First Received:	May 14, 2004
Last Updated:	December 13, 2008
ClinicalTrials.gov Identifier:	NCT00083187
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent adult acute myeloid leukemia
untreated adult acute myeloid leukemia
atypical chronic myeloid leukemia
chronic myelomonocytic leukemia
myelodysplastic/myeloproliferative disease, 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)

Study placed in the following topic categories:

Neural Tube Defects
Precancerous Conditions
Chronic myelogenous leukemia
Hydroxyurea
Nervous System Malformations
Chronic myelomonocytic leukemia
Leukemia, Myeloid, Acute
Leukemia
Preleukemia
Neoplasm Metastasis
Acute myeloid leukemia, adult
Congenital Abnormalities
Acute myelocytic leukemia
Myelodysplastic syndromes

Hematologic Diseases
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes
Myelodysplasia
Myeloproliferative Disorders
Acute myelogenous leukemia
Leukemia, Myeloid
Recurrence
Myelodysplastic myeloproliferative disease
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neural tube defect, folate-sensitive
Myelodysplastic-Myeloproliferative Diseases
Bone Marrow Diseases

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Disease
Antisickling Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Nervous System Diseases
Hematologic Agents

Enzyme Inhibitors
Pharmacologic Actions
Neoplasms
Pathologic Processes
Syndrome
Therapeutic Uses
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 15, 2009