VNP40101M Followed by Cytarabine in Treating Older Patients With Acute Myeloid Leukemia

Sponsor

Vion Pharmaceuticals (Industry)

Overall Status

Unknown status

CT.gov ID

NCT00354276

Collaborator

(none)

Enrollment

Locations

28.3

Patients Per Site

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as VNP40101M and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving VNP40101M followed by cytarabine may kill more cancer cells.

PURPOSE: This phase II trial is studying how well VNP40101M followed by cytarabine works in treating older patients with acute myeloid leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: cytarabine Drug: laromustine	Phase 2

Detailed Description

OBJECTIVES:

Primary

Determine the complete response rate in older patients with poor-risk, de novo acute myeloid leukemia treated with VNP40101M as induction therapy followed by cytarabine as consolidation therapy.

Secondary

Determine the probability of overall survival, leukemia-free survival, and progression-free survival of patients treated with this regimen.
Determine the safety of this regimen in these patients.

OUTLINE: This is an open-label, multicenter study.

Induction therapy: Patients receive VNP40101M IV over 60 minutes on day 1 (course 1). Patients without evidence of disease progression who have responding but residual disease receive a second course of VNP40101M once between days 35-60. Patients achieving complete response or partial response after induction therapy proceed to consolidation therapy.
Consolidation therapy: Beginning between days 45-90, patients receive cytarabine IV continuously over 5 days (course 1). Patients may receive a second course of cytarabine at the discretion of the investigator.

After completion of study treatment, patients are followed periodically for up to 36 months.

PROJECTED ACCRUAL: A total of 85 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

85 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Study of Cloretazine® (VNP40101M) for Elderly Patients With De Novo Poor Risk Acute Myelogenous Leukemia

Study Start Date :

May 1, 2006

Anticipated Primary Completion Date :

Dec 1, 2008

Outcome Measures

Primary Outcome Measures

Complete response rate []

Secondary Outcome Measures

Leukemia-free survival []

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed de novo acute myeloid leukemia (AML)
No acute promyelocytic leukemia [t(15;17)]
No favorable cytogenetics, including t(15;17), t(8;21), or inv 16
No secondary AML, defined as having a history of an antecedent hematologic disorder (myelodysplastic syndromes [MDS] or myeloproliferative disease), or history of prior chemotherapy or radiation for a disease other than AML
Must have ≥ 1 of the following poor-risk features:
Any of the following unfavorable cytogenetics:
Del (5q)/-5q
-7/del(7q)
Abnormal 3q, 9q, 11q, 20q, 21q, or 17p
t(6;9)
t(9;22)
Trisomy 8
Complex karyotypes (≥ 3 unrelated abnormalities)
At least 70 years of age
ECOG performance status (PS) of 2
Cardiac dysfunction* that would limit the use of anthracycline therapy, as defined by any of the following:
Ejection fraction ≤ 50%
History of significant coronary artery disease, defined as ≥ 1 vessel stenosis requiring medical treatment, stent placement, or surgical bypass graft
History of congestive heart failure or myocardial infarction
Significant arrhythmia, including any of the following:
Atrial flutter (excluding atrial fibrillation)
Sick sinus syndrome
Ventricular arrhythmia
Heart valve disease
Mitral valve prolapse allowed
Other heart disease, at the discretion of the principal investigator
Pulmonary dysfunction not related to AML, defined by 1 of the following:
DLCO and/or FEV_1 < 80% and ≥ 50% normal range
Dyspnea on slight activity or at rest
Requires oxygen
Hepatic dysfunction related to chronic hepatitis or liver cirrhosis
Other organ dysfunction or comorbidity that precludes standard cytotoxic induction treatment (e.g., "3+7"), at the discretion of the principal investigator NOTE: *Patients with a history of heart disease as defined above must be on appropriate medication and have their disease under control
No known CNS disease

PATIENT CHARACTERISTICS:

ECOG PS 0-2
AST and ALT ≤ 5 times upper limit of normal
Bilirubin ≤ 2.0 mg/dL
Creatinine ≤ 2.0 mg/dL
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 6 months after completion of study treatment
No active, uncontrolled infection
Patients with an infection who are under active treatment with antibiotics and whose infections are controlled are eligible
Chronic hepatitis allowed
No clinical evidence of ongoing second malignancy unrelated to AML or MDS
No evidence of left bundle branch block on screening ECG
No obligate use of cardiac pacemaker or atrial fibrillation

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
At least 24 hours since prior metronidazole
No prior low-dose, single-agent, cytotoxic chemotherapy (e.g., cytarabine, decitabine, or azacitidine)
No concurrent disulfiram
No other concurrent standard or investigational therapy for AML except for the following:
Concurrent hydroxyurea to control rising white blood cell counts
Dosage must be 4-6 grams daily for up to 4 days
Concurrent leukapheresis to control blast cell counts
Must be completed within the first 5 days of study therapy
No more than 2 procedures per day or 4 procedures total
Investigational supportive care agents (e.g., antimicrobials or antifungal agents), at the discretion of the protocol sponsor

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California	United States	90095-1781
2	Hopital Haut Leveque	Pessac		France	33604
3	University Hospital of Wales	Cardiff	Wales	United Kingdom	CF14 4XW