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

Primary Purpose

Leukemia

Status

Completed

Phase

Phase 1

Locations

France

Study Type

Interventional

Intervention

amsacrine

busulfan

cytarabine

daunorubicin hydrochloride

laromustine

melphalan

mitoxantrone hydrochloride

allogeneic hematopoietic stem cell transplantation

autologous hematopoietic stem cell transplantation

About this trial

This is an interventional treatment trial for Leukemia focused on measuring adult acute myeloid leukemia with 11q23 (MLL) abnormalities, untreated adult acute myeloid leukemia

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept 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

PRIOR CONCURRENT THERAPY:

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

Sites / Locations

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

Outcomes

Primary Outcome Measures

Dose-limiting toxicity (phase I)

Rate of complete remission (phase II)

Secondary Outcome Measures

Full Information

NCT ID

NCT00840684

First Posted

February 7, 2009

Last Updated

May 12, 2011

Sponsor

Institut Paoli-Calmettes

1. Study Identification

Unique Protocol Identification Number

NCT00840684

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

July 2009

Overall Recruitment Status

Completed

Study Start Date

January 2009 (undefined)

Primary Completion Date

May 2011 (Actual)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor

Institut Paoli-Calmettes

4. Oversight

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Leukemia

Keywords

adult acute myeloid leukemia with 11q23 (MLL) abnormalities, untreated adult acute myeloid leukemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

135 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

amsacrine

Intervention Type

Drug

Intervention Name(s)

busulfan

Intervention Type

Drug

Intervention Name(s)

cytarabine

Intervention Type

Drug

Intervention Name(s)

daunorubicin hydrochloride

Intervention Type

Drug

Intervention Name(s)

laromustine

Intervention Type

Drug

Intervention Name(s)

melphalan

Intervention Type

Drug

Intervention Name(s)

mitoxantrone hydrochloride

Intervention Type

Procedure

Intervention Name(s)

allogeneic hematopoietic stem cell transplantation

Intervention Type

Procedure

Intervention Name(s)

autologous hematopoietic stem cell transplantation

Primary Outcome Measure Information:

Title

Dose-limiting toxicity (phase I)

Title

Rate of complete remission (phase II)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Norbert Vey, MD

Organizational Affiliation

Institut Paoli-Calmettes

Official's Role

Principal Investigator

Facility Information:

Facility Name

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

City

Marseille

ZIP/Postal Code

13273

Country

France

12. IPD Sharing Statement

Learn more about this trial

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

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