Liposomal Anthracyclin in the Treatment of Elderly ALL

Study Overview
=================
Brief Summary
-----------------
Phase II multicentric study comparing VAD regimen with continuous infusion over 96 hours of doxorubicin, vincristine and dexamethasone to a 90 minutes infusion of equivalent doses of Dox li-PEG, bolus infusion of vincristine and dexamethasone

Detailed Description
-----------------
Patients aged 55 years or over will be assessed for response to steroids from day -7 to day 0 During steroid therapy, Ph status will be determinated : patients with Ph+ ve ALL will be treated according to the another French Protocol while patients with Ph-ve ALL will be included in the caelyx protocol and randomly allocated to induction with VAD or with vadox-li-Peg (caelyx). A second course of induction therapy with VAD+ cyclophosphamide of Vadox-li-peg+ cyclophosphamide(according to the initial randomization arm) will then be given to all patients. Consolidation therapy included 2 courses of vad or of vadox-li-Peg , according to the initial random allocation, followed by two courses of cytarabine,cyclophosphamide and thioguanine. During induction and consolidation therapy, doxorubicin and liposomal pegylated doxorubicin pharmacokinetics will be assessed in all patients. Treatment of occult CNS invasion includes skull radiotherapy and 6 intrathecal injections(steroÏds+methotrexate) A two years maintenance course with 6 mercaptopurine and methotrexate will then be offered to all patients.

Official Title
-----------------
A Multicentric Phase II-III Randomized Study Safety of Intraveinous Liposomal Pegylated Doxorubicin Versus Continuous Infusion of Doxorubicin During Induction Treatment of Acute Lymphoblastic Leukemia in Patients

Conditions
-----------------
Acute Lymphoblastic Leukemia

Intervention / Treatment
-----------------
* Drug: Doxorubicine
* Drug: Doxorubicine pegylated


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 55 years of age and older ECOG performance </=2 or >/=3 VIH negative Absence of previous ALL treatment Informed consent signed SGPT and Bilirubin < 4x upper limit of normal Normal creatinine for age cardiac state compatible with anthacyclin Exclusion Criteria: ALL with Philadelphia Chromosome ALL3 CML blasts crisis Cardiac insufficiency and/ or left ventricular ejection fraction < 50% Evolutive infection Presence of other evolutifs cancer or ongoing treatment mental status incompatible with inform consent

Ages Eligible for Study
-----------------
Minimum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: doxorubicine<br>VAD | Drug: Doxorubicine<br>* 9mg/m² J1 J4 2 COURSES<br>|
| Experimental: Doxorubicine pegylated<br>Doxorubicine pegylated 40 MG/M² J1 | Drug: Doxorubicine pegylated<br>* 40 MG/M² J1 2 courses<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients alive by day 113 ( last injection of anthracycline ) and having received a full course of induction/consolidation therapy |  | 113 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematological and cutaneous adverse evnts of both types of chemotherapy |  | 113 days | 
| Resistance to chemotherapy |  | 113 days | 
| Complete response rates |  | 113 days | 
| Disease free and overall survival |  | 4 months | 
| Economical study |  | 113 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ALL, Chemotherapy, Pharmacokinetics of doxorubicin (pegylated or not), elderly ALL