Lomustine and Intermediate Dose Cytarabine in Older Patients With AML

Condition(s) targeted: Acute Myeloid Leukemia

Intervention: Lomustine, intermediate dose cytarabine (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS

Official(s) and/or principal investigator(s):
JOSY REIFFERS, MD, Principal Investigator, Affiliation: CHU Haut-Leveque Pessac 33604 France

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.

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 design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: 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

Secondary outcome: 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.

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 .

Minimum age: 60 Years. Maximum age: N/A. Gender(s): Both.

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

Josy REIFFERS, MD MS, Pessac 33604, France

Starting date: July 1995
Ending date: May 2007
Last updated: May 29, 2007