Laromustine, Daunorubicin, and Cytarabine in Treating Patients With Acute Myeloid Leukemia
Information source: National Cancer Institute (NCI)
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Leukemia
Intervention: amsacrine (Drug); busulfan (Drug); cytarabine (Drug); daunorubicin hydrochloride (Drug); laromustine (Drug); melphalan (Drug); mitoxantrone hydrochloride (Drug); allogeneic hematopoietic stem cell transplantation (Procedure); autologous hematopoietic stem cell transplantation (Procedure)
Phase: Phase 1/Phase 2
Status: Completed
Sponsored by: Institut Paoli-Calmettes Official(s) and/or principal investigator(s): Norbert Vey, MD, Principal Investigator, Affiliation: Institut Paoli-Calmettes
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.
Clinical Details
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 design: Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Dose-limiting toxicity (phase I)Rate of complete remission (phase II)
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 60 Years.
Gender(s): Both.
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
Locations and Contacts
Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes, Marseille 13273, France
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: January 2009
Last updated: May 12, 2011
|