Laromustine, Daunorubicin, and Cytarabine in Treating Patients With Acute Myeloid Leukemia

Sponsor

Institut Paoli-Calmettes (Other)

Overall Status

Completed

CT.gov ID

NCT00840684

Collaborator

(none)

135

Enrollment

Location

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as laromustine, daunorubicin, 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 more than one drug (combination chemotherapy) may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of laromustine when given together with daunorubicin and cytarabine in treating patients with acute myeloid leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: amsacrine Drug: busulfan Drug: cytarabine Drug: daunorubicin hydrochloride Drug: laromustine Drug: melphalan Drug: mitoxantrone hydrochloride Procedure: allogeneic hematopoietic stem cell transplantation Procedure: autologous hematopoietic stem cell transplantation	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

Primary

To determine the dose of laromustine that can be combined with daunorubicin hydrochloride and cytarabine in patients with previously untreated acute myeloid leukemia with unfavorable cytogenetics. (Phase I)
To determine the complete remission rate of this regimen as induction therapy. (Phase II)

Secondary

To determine the complete response rate.
To determine the safety profile of this regimen.
To determine the overall and relapse-free survival.
To evaluate the prognostic value of the molecular markers FLT3, duplications of MLL, and Evi-1.

OUTLINE: This is a multicenter, phase I dose-escalation study of laromustine followed by a phase II study.

Induction treatment: Patients receive laromustine IV on day 4, daunorubicin hydrochloride IV on days 1-3, and cytarabine IV continuously on days 1-7. Patients not attaining complete remission (CR) after first induction receive a second induction treatment comprising daunorubicin hydrochloride IV on days 1-3 and cytarabine IV twice daily on days 1-4. Patients in CR after 1 or 2 induction treatments proceed to consolidation treatment.
Consolidation treatment: Patients receive mini-consolidation treatment comprising amsacrine on day 1 and cytarabine IV twice daily on days 1-5 followed by 2 courses of continuing consolidation treatment comprising mitoxantrone hydrochloride on days 1 and 2 and cytarabine IV over 12 hours on days 1-5.
Allogeneic or autologous stem cell transplantation: Patients receive busulfan four times daily for 4 days and melphalan followed by allogeneic or autologous stem cell transplantation.

After completion of study treatment, patients are followed periodically for 5 years.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

135 participants

Allocation:

Non-Randomized

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A PHASE I-II MULTICENTER STUDY OF THE CLORETAZINE-DAUNORUBICIN-ARACYTINE COMBINATION FOR THE TREATMENT OF ACUTE MYELOID LEUKEMIA (AML) WITH UNFAVORABLE CYTOGENETICS

Study Start Date :

Jan 1, 2009

Actual Primary Completion Date :

May 1, 2011

Outcome Measures

Primary Outcome Measures

Dose-limiting toxicity (phase I) []
Rate of complete remission (phase II) []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of acute myeloid leukemia (AML)
Untreated disease
No promyelocytic AML
Unfavorable prognosis, defined as at least one of the following:
Cytogenetic abnormalities including -5/5q-, -7/7q-, 3q, 11q23, t(6;9), and complex abnormalities (≥ 3 clonal abnormalities), excluding t(9;11)
Baseline hyperleukocytosis ≥ 100 g/L or progression of leukocytosis or extra-medullary localizations despite treatment with hydroxyurea
No AML with favorable or intermediate prognosis
No AML secondary to myelodysplastic syndrome diagnosed within the past 3 months or myeloproliferative syndrome

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Total bilirubin < 35 μmol/L
Transaminases < 2.5 times upper limit of normal in the absence of leukemia-related abnormalities
Creatinine < 170 μmol/L OR creatinine clearance ≥ 50 mL/min in the absence of leukemia-related abnormalities
Not pregnant or nursing
Normal cardiac function by LVEF (echographic ≥ 40% or isotopic ≥ 50%)
Affiliated with a social security system
No uncontrolled or severe cardiovascular disease, including any of the following:
Myocardial infarction within the past 3 months
Cardiac insufficiency
Uncontrolled arrhythmia
No other active cancer within the past year except for basal cell carcinoma of the skin or epithelioma in situ of the cervix
No patients deprived of freedom or under guardianship (including temporary guardianship)
No psychological, familial, geographical, or social situations that preclude follow-up
No other contraindications to study treatment