Clinical trial · Interventional

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

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

NCT00083187CI-TRIAL-00011405completedPhase 2ClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Summary

Brief summary (as posted)

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

Conditions (3)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Leukemia	Leukemia	ONTOLOGY_EXACT	0.90
Myelodysplastic/Myeloproliferative Neoplasms	Myelodysplastic/Myeloproliferative Neoplasm	CURATED_BROADER	0.80
Myelodysplastic Syndromes	Myelodysplastic Syndrome	ALIAS	0.90

Interventions

Interventions (2)

Intervention	Type	Mapped drug	Match
hydroxyurea	Drug	Hydroxyurea	ALIAS
laromustine	Drug	—	UNRESOLVED

Design

Arms and outcomes

Arms (0)

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Primary outcomes (3)

measure
Complete response rate
measure
Toxic effects
measure
Pharmacokinetics

Eligibility

Eligibility (as posted)

Sex: All
Minimum age: 18 Years

Show eligibility criteria text

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

References

Publications (2)

RESULTGerson 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.
RESULTGiles 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

Registry

Dates and enrollment

Start: Nov 1, 2005
Primary completion: Jan 1, 2007
Completion: Aug 1, 2008
First posted: May 17, 2004
Last update posted: Jul 18, 2013
Enrollment: 230 (estimated)
Lead sponsor: Vion Pharmaceuticals INDUSTRY
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)

Data updated 22 days agoSource updated Jul 18, 2013source: clinicaltrials

Locations

Locations by country (5)

Country	Sites	Recruiting
United States	3	0
United Kingdom