Phase III Study Treatment of CLL B and C

GOELAMS LLC98 is a prospective randomized trial comparing in previously untreated B and C Binet stages B-CLL and on an intent to treat basis two strategies. Conventional chemotherapy consisted of six monthly courses of CHOP, followed by 6 CHOP courses every other 3 months in case of response. Experimental arm consisted of high dose therapy with autologous CD34+ purified progenitor cell support, used as consolidation of Complete Remission or Very Good Partial Response obtained after 3 monthly courses of CHOP, followed by 3 to 6 monthly-courses of fludarabine in case of insufficient response.

The aim of the prospective randomized GOELAMS LLC 98 trial reported here was to compare two therapeutic strategies in previously untreated B and C Binet stages B-CLL patients less than 60 years old. Conventional chemotherapy (Arm A) consisted of six monthly courses of CHOP, i.e. vincristin IV 1 mg/m2 on day 1, doxorubicin IV 25 mg/m2 on day 1, cyclophosphamide (Cy) 300 mg/m2 and prednisone 40 mg/m2 both given orally from day 1 to day 5, followed by 6 CHOP courses every other 3 months in case of response. Fludarabine (25 mg/m2 /d IV for 5 consecutive days) was used in case of non response (stable disease or progression) after 3 CHOP courses. This conventional therapy was compared to high dose therapy with autologous CD34+ purified progenitor cell support (Arm B), used as consolidation of Complete Remission (CR) or Very Good Partial Response (VGPR, defined by >50 % tumoral response and bone marrow lymphocyte infiltration <30%) obtained after 3 monthly courses of CHOP. In the absence of CR or VGPR, 3 to 6 monthly-courses of fludarabine were performed before mobilization with Cy 4 g/m2 + G-CSF administration. The conditioning regimen included TBI 12 Gy and Cy 60 mg /kg /d for 2 days.

• No Intervention: A
  ¨Chemotherapy by 12 courses of CHOP
• Active Comparator: B
  ¨Chemotherapy by 3 courses of CHOP, intensification and autograft
  Intervention: Procedure: Stem cells autograft

Inclusion Criteria:

• CLL with Lymphocitis > 15.10 9/L
• B-CLL stage B or C
• Patients > 18 years old and < 60 years old
• No previous treatment of CLL
• ECOG performance status < 2
• Good cardiac function
• Patient's written informed consent

Exclusion Criteria:

• B-CLL stage A
• Age > 60 years old
• previous treatment of CLL
• ECOG performance status > 2
• Cardiac or pneumo Insufficency
• hepatic or renal Insufficency
• Seropositivity HIV
• Previous other malignancy
• Fertile male and female patients who cannot or do not wish to use an effective method of contraception
• Any coexisting medical or psychological condition that would preclude participation to the required study procedures
• NOt signed Patient's informed consent