Clinical trial NCT00600977: Liposomal Anthracyclin in the Treatment of Elderly ALL
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Lymphoblastic Leukemia
Keywords: ALL
Chemotherapy
Pharmacokinetics of doxorubicin (pegylated or not)
elderly ALL
Lead sponsor: French Innovative Leukemia Organisation
Sponsor class: OTHER
First posted: 2008-01-25
Enrollment: 60
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of patients alive by day 113 ( last injection of anthracycline ) and having received a full course of induction/consolidation therapy
timeFrame: 113 days
Secondary outcomes:
measure: Hematological and cutaneous adverse evnts of both types of chemotherapy
timeFrame: 113 days
measure: Resistance to chemotherapy
timeFrame: 113 days
measure: Complete response rates
timeFrame: 113 days
measure: Disease free and overall survival
timeFrame: 4 months
measure: Economical study
timeFrame: 113 days
Other outcomes:
Locations:
city: Angers
country: France
facility: Regional university hospital
Study officials:
affiliation: French Innovative Leukemia Organisation
name: Mathilde HUNAULT BERGER, RN
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hunault-Berger M, Leguay T, Thomas X, Legrand O, Huguet F, Bonmati C, Escoffre-Barbe M, Legros L, Turlure P, Chevallier P, Larosa F, Garban F, Reman O, Rousselot P, Dhedin N, Delannoy A, Lafage-Pochitaloff M, Bene MC, Ifrah N, Dombret H; Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL). A randomized study of pegylated liposomal doxorubicin versus continuous-infusion doxorubicin in elderly patients with acute lymphoblastic leukemia: the GRAALL-SA1 study. Haematologica. 2011 Feb;96(2):245-52. doi: 10.3324/haematol.2010.027862. Epub 2010 Oct 22.