Autologous Stem Cell Transplantation in Chronic Lymphocytic Leukemia
Condition: Chronic Lymphocytic Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Study type: Interventional
Phase: Phase 3

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).
    

Intervention name(s): Autologous stem cell transplantation; DHAP rescue and Autologous stem cell transplantation; DHAP rescue and F+C
Intervention type(s): Procedure; Procedure; Procedure
Intervention description(s): TBI (10 grays, d-3-1), cyclophosphamide (60 mg/sqm d-5-4); 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); 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)
Other intervention name(s): ABMT; cisplatin; dexamethasone; cytarabine; Fludarabine; Cyclophosphamide
Intervention MeSH terms: Cytarabine; Dexamethasone; Cyclophosphamide; Cisplatin; Fludarabine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Chronic lymphocytic leukemia,; autologous stem cell transplantation