Auto-LLC 2001: Autologous Stem Cell Transplantation in Chronic Lymphocytic Leukemia

Sponsor

University Hospital, Caen (Other)

Overall Status

Completed

CT.gov ID

NCT00931645

Collaborator

Direction Générale de la Santé, France (Other)

241

Enrollment

Location

Arms

Duration (Months)

2.6

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia	Procedure: Autologous stem cell transplantation Procedure: DHAP rescue and Autologous stem cell transplantation Procedure: DHAP rescue and F+C	Phase 3

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).

Study Design

Study Type:

Interventional

Actual Enrollment :

241 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Apr 1, 2001

Actual Primary Completion Date :

Dec 1, 2007

Actual Study Completion Date :

Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Complete responders watch and wait policy
Experimental: arm 2: complete responders patients ABMT : TBI, 10 grays d-3-1 & cyclophosphamide 60 mg/sqm d-5-4	Procedure: Autologous stem cell transplantation TBI (10 grays, d-3-1), cyclophosphamide (60 mg/sqm d-5-4) Other Names: ABMT
Experimental: Non CR patients arm 3 Rescue chemotherapy and ABMT (see arm 2)	Procedure: DHAP rescue and Autologous stem cell transplantation 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) Other Names: cisplatin dexamethasone cytarabine
Active Comparator: Non CR patients at random : arm 4 Rescue DHAP, F+C	Procedure: DHAP rescue and F+C 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 Names: Fludarabine Cyclophosphamide

Outcome Measures

Primary Outcome Measures

Progression free survival [3 year]

Secondary Outcome Measures

Overall survival, response after completion of scheduled treatment, tolerance and adverse events, quality of life, prognostic factors for response and survival. [36 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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