Autologous Stem Cell Transplantation in Chronic Lymphocytic Leukemia

Chronic Lymphocytic Leukemia Clinical Trial

— Auto-LLC 2001  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00931645
• Other study ID #: SFGMTC
• Secondary ID: PHRC
• Status: Completed
• Phase: Phase 3
• First received: June 29, 2009
• Last updated: July 1, 2009
• Start date: April 2001
• Est. completion date: December 2008

Study information

• Verified date: July 2009
• Source: University Hospital, Caen
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 241
• Est. completion date: December 2008
• Est. primary completion date: December 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Procedure:
• Autologous stem cell transplantation
TBI (10 grays, d-3-1), cyclophosphamide (60 mg/sqm d-5-4)
• 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)
• 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)

Locations

Country	Name	City	State
France	DBIM Hopital Saint Louis	Paris

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Caen	Direction Générale de la Santé, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival		3 year	Yes
Secondary	Overall survival, response after completion of scheduled treatment, tolerance and adverse events, quality of life, prognostic factors for response and survival.		36 months	Yes