Autologous Stem Cell Transplantation in Chronic Lymphocytic Leukemia

Study Overview
=================
Brief Summary
-----------------
Phase III trial evaluating the role of autologous stem cell transplantation in previously untreated patients under 65 years with stage B and C B-cell chronic lymphocytic leukemia. Endpoints of the trial : major : progression free survival at 3 years secondary : overall survival, tolerance, prognostic factors according to baseline clinical stage and biological characteristics (IgHv mutational status, expression of ZAP70 and CD38, cytogenetics).

Detailed Description
-----------------
All registered patients will be treated with 6 monthly courses of chemotherapy. First three ones will be a CHOP regimen with half dosage of adriamycin, as previously published (Effectiveness of CHOP regimen in advanced untreated chronic lymphocytic leukemia. French Cooperative Group on Chronic Lymphocytic Leukemia. Lancet ; 1986, i : 1346-1349), followed by three subsequent courses with IV fludarabine (25 mg/sqm d1-5). Patients in CR (NCI, 1996, including CAT scan evaluation) will be then randomized to surveillance without additional treatment or autologous stem cell transplantation using peripheral stem cells collected after the three first courses of chemotherapy, and/or after the completion of the six courses when necessary. For patients not in CR after the six courses, a rescue regimen with the DHAP association ( cisplatin, 100 mg/sqm d1, cytarabine 2 g/sqm d2, dexamethasone 40 mg/sqm d1-4) will precede an additional stem cell collection if necessary, and patient will be randomized between autologous stem cell transplantation and three additional courses of an association of fludarabine (25 mg/sqm d1-3) and cyclophosphamide (300 mg/sqm d1-3). Conditioning regimen will associate TBI (10 grays, d -3-1) and cyclophosphamide (60 mg/sqm d-5-4). Evaluation for response wil be performed before randomisation and two months after completion of therapy in each arm. Follow-up data will be registered and monitored every three month during the first year, and then every six month. Criteria for evaluation of response will use the NCI system (1996).

Official Title
-----------------
Randomized Phase III Trial Evaluating the Role of Autologous Stem Cell Transplantation in Previously Untreated Patients With Stage B and C Chronic Lymphocytic Leukemia

Conditions
-----------------
Chronic Lymphocytic Leukemia

Intervention / Treatment
-----------------
* Procedure: Autologous stem cell transplantation
* Procedure: DHAP rescue and Autologous stem cell transplantation
* Procedure: DHAP rescue and F+C


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: patients with stage B & C CLL, 18- 65 years. previously untreated given written informed consent Exclusion Criteria: Childbearing women OMS Performance status > 2 Binet stage A Autoimmune hemolytic anemia Active or previous (< 5 years) malignant disease, except cutaneous cell carcinoma. Previous CLL treatment HIV seropositivity Abnormal renal or liver function tests (creatinine > 1,5N, transaminases > 2N, bilirubin > 1,5N) Cardiac failure (ejection fraction < 50%) Lung disease or perturbed ventilation tests

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 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 |
| --- | --- |
| No Intervention: Complete responders<br>watch and wait policy | |
| Experimental: arm 2: complete responders patients<br>ABMT : TBI, 10 grays d-3-1 & cyclophosphamide 60 mg/sqm d-5-4 | Procedure: Autologous stem cell transplantation<br>* TBI (10 grays, d-3-1), cyclophosphamide (60 mg/sqm d-5-4)<br>* Other names: ABMT;|
| Experimental: Non CR patients arm 3<br>Rescue chemotherapy and ABMT (see arm 2) | Procedure: DHAP rescue and Autologous stem cell transplantation<br>* DHAP :IV cisplatin 100 mg/sqm d1, IV cytarabine 2 g/sqm d2,, IV dexamethasone 40 mg/sqm d1-4, TBI (10 grays d-3-1), cyclophosphamide (60 mg/sqm d-5-4)<br>* Other names: cytarabine;|
| Active Comparator: Non CR patients at random : arm 4<br>Rescue DHAP, F+C | Procedure: DHAP rescue and F+C<br>* DHAP :IV cisplatin 100 mg/sqm d1, IV Cytarabine 2 g/sqm d2, IV dexamethasone 40 mg/sqm d1-4, Followed by 3 monthly cycles with IV d1-3 fludarabine (25 mg/sqm) & cyclophosphamide (300 mg/sqm)<br>* Other names: Cyclophosphamide;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival |  | 3 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival, response after completion of scheduled treatment, tolerance and adverse events, quality of life, prognostic factors for response and survival. |  | 36 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic lymphocytic leukemia,, autologous stem cell transplantation