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

Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00083187
• Other study ID #: VION-CLI-033
• Secondary ID: CDR0000365510
• Status: Completed
• Phase: Phase 2
• First received: May 14, 2004
• Last updated: July 17, 2013
• Start date: November 2005
• Est. completion date: August 2008

Study information

• Verified date: August 2008
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 230
• Est. completion date: August 2008
• Est. primary completion date: January 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Neoplasms
• Myeloproliferative Disorders
• Preleukemia

Intervention

Drug:
• hydroxyurea

• laromustine

Locations

Country	Name	City	State
France	Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes	Marseille
United Kingdom	King's College Hospital	London	England
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	M.D. Anderson Cancer Center at University of Texas	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Vion Pharmaceuticals

Countries where clinical trial is conducted

United States,  France,  United Kingdom, 

References & 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 Annu

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 sulfonylhydr — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete response rate			No
Primary	Toxic effects			Yes
Primary	Pharmacokinetics			No