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

17. juli 2013 oppdatert av: Vion Pharmaceuticals

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

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.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

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.

Studietype

Intervensjonell

Registrering (Forventet)

230

Fase

Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

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

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

Primært formål: Behandling
Masking: Ingen (Open Label)

Hva måler studien?

Primære resultatmål

Resultatmål
Farmakokinetikk
Fullstendig svarprosent
Giftige effekter

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Vion Pharmaceuticals

Etterforskere

Studiestol: Francis J. Giles, MD, M.D. Anderson Cancer Center

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

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. doi: 10.1200/JCO.2006.07.0961. Epub 2006 Dec 4.

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. november 2005

Primær fullføring (Faktiske)

1. januar 2007

Studiet fullført (Faktiske)

1. august 2008

Datoer for studieregistrering

Først innsendt

14. mai 2004

Først innsendt som oppfylte QC-kriteriene