Clinical trial NCT00480064: Lomustine and Intermediate Dose Cytarabine in Older Patients With AML
Official title: Randomized Prospective Study of Adding Lomustine to Idarubicin and Cytarabine for Induction Chemotherapy and Adding Intermediate Dose Cytarabine to Consolidation in Older Patients With Acute Myeloid Leukaemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Myeloid Leukemia
Keywords: AML
older patients
lomustine
Lead sponsor: French Innovative Leukemia Organisation
Sponsor class: OTHER
First posted: 2007-05-30
Enrollment: 360
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A multicenter randomized trial was performed comparing induction therapy (IC: Idarubicin and Cytarabine, 5+7) to ICL (the same drugs plus lomustine (CCNU), 200mg\\m2 orally at day 1). Patients in complete remission (CR) were then randomized to receive either maintenance therapy or intensification with intermediate-dose cytarabine and idarubicin followed by maintenance therapy.

Detailed description: Induction therapy: Patients were randomized to receive idarubicin plus cytarabine (IC) or the same drugs plus lomustine (ICL), the latter given at the dose of 200 mg/m2 orally at day 1. Patients with persistent leukemia in the bone marrow, defined by at least 20% marrow cellularity with more than 5% blasts on day 14 or at a subsequent time point following initiation of induction therapy, received a second course of induction chemotherapy identical to the initial induction course. Non-responders to the second induction course were taken off the protocol.

Consolidation therapy: After completing induction treatment, patients who were in complete remission after 1 or 2 induction courses received a course of consolidation (IC') therapy with idarubicin and subcutaneous cytarabine. Subsequently, if stable remission persisted, the patients received maintenance therapy or maintenance therapy preceded by a second consolidation (IIC) with intermediate-dose cytarabine. Randomization was performed as soon as CR was achieved.

Maintenance therapy: This was conducted in all patients with persisting CR one month after completing the first (IC) or second (IIC) consolidation and consisted of the following: five courses of combination chemotherapy at 1, 3, 6, 9 and 13 months from the last consolidation, namely cytarabine (subcutaneously) and idarubicin and between these courses for one year: a continuous regimen of methotrexate and 6-mercaptopurine, as alternating 10 day-courses .

Eligibility criteria: Inclusion Criteria:

* Patients aged 60 years and older with de novo AML according to FAB criteria
* With normal cardiac function with left ventricular ejection fraction \>= 50%, absence of unstable cardiac arrhythmia or unstable angina.
* Unimpaired renal (creatinin \<180µmol\\L)
* Unimpaired liver (bilirubin \<35µmol\\L) functions.
* Performance status \<3
* Signed and dated informed consent.

Exclusion Criteria:

* Acute promyelocytic leukemia
* Patients with myeloproliferative syndromes prior to diagnosis of AML
* Patients who previously had myelodysplastic syndrome
* Patients pretreated with chemo- or radiotherapy
* Performance status \<2
* Positive serology for HIV

Primary outcomes:
measure: Primary Outcomes: The primary objective of this study was to assess the ability of lomustine to increase the CR rate and to improve overall survival
timeFrame: 13 months
Secondary outcomes:
measure: Secondary Outcomes: The secondary objective was to test intermediate-dose cytarabine on survival, and to analyze the impact of prognostic factors on CR and survival.
timeFrame: 13 months
Other outcomes:
Locations:
city: Pessac
country: France
facility: Josy REIFFERS, MD MS
Study officials:
affiliation: CHU Haut-Leveque Pessac 33604 France
name: JOSY REIFFERS, MD
role: PRINCIPAL_INVESTIGATOR
References: