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

NCT ID: NCT00840684

Last Updated: 2011-05-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 135 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31

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.

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.

Conditions

Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

amsacrine

Intervention Type: DRUG

busulfan

Intervention Type: DRUG

cytarabine

Intervention Type: DRUG

daunorubicin hydrochloride

Intervention Type: DRUG

laromustine

Intervention Type: DRUG

melphalan

Intervention Type: DRUG

mitoxantrone hydrochloride

Intervention Type: DRUG

allogeneic hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

autologous hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

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

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Prior hydroxyurea allowed
• No concurrent disulfiram
• No concurrent participation in another study with an experimental drug

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institut Paoli-Calmettes

OTHER

Sponsor Role: lead

Principal Investigators

Norbert Vey, MD

Role: PRINCIPAL_INVESTIGATOR

Institut Paoli-Calmettes

Locations

Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes

Marseille, , France

Countries

France

Other Identifiers

IPC-LAM-HR

Identifier Type: -

Identifier Source: secondary_id

IPC-2006-007

Identifier Type: -

Identifier Source: secondary_id

INCA-RECF0902

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2007-001082-15

Identifier Type: -

Identifier Source: secondary_id

CDR0000634230

Identifier Type: -

Identifier Source: org_study_id