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

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00840684
First received: February 7, 2009
Last updated: May 12, 2011
Last verified: July 2009
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Dose-limiting toxicity (phase I) [ Designated as safety issue: Yes ]
  • Rate of complete remission (phase II) [ Designated as safety issue: No ]

Estimated Enrollment: 135
Study Start Date: January 2009
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
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

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00840684

Locations
France
Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
Marseille, France, 13273
Sponsors and Collaborators
Institut Paoli-Calmettes
Investigators
Principal Investigator: Norbert Vey, MD Institut Paoli-Calmettes
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00840684     History of Changes
Other Study ID Numbers: CDR0000634230, IPC-LAM-HR, IPC-2006-007, INCA-RECF0902, EUDRACT-2007-001082-15
Study First Received: February 7, 2009
Last Updated: May 12, 2011
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
untreated adult acute myeloid leukemia

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Mitoxantrone
Daunorubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on September 16, 2014