Clinical trial NCT00931645: Autologous Stem Cell Transplantation in Chronic Lymphocytic Leukemia
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Lymphocytic Leukemia
Keywords: Chronic lymphocytic leukemia,
autologous stem cell transplantation
Lead sponsor: University Hospital, Caen
Sponsor class: OTHER
Collaborators: name: Direction Générale de la Santé, France
First posted: 2009-07-02
Enrollment: 241
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Progression free survival
timeFrame: 3 year
Secondary outcomes:
measure: Overall survival, response after completion of scheduled treatment, tolerance and adverse events, quality of life, prognostic factors for response and survival.
timeFrame: 36 months
Other outcomes:
Locations:
city: Paris
country: France
facility: DBIM Hopital Saint Louis
Study officials:
affiliation: Hospital Victor Dupouy Argenteuil, France
name: Sutton Laurent, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CaenUH, France
name: Leporrier Michel, MD
role: STUDY_CHAIR
References: