Allogeneic Stem Cell Transplantation in Chronic Lymphocytic Leukemia

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

Chemo-Immunotherapy With Allogeneic Blood Stem Cell Transplantation in Patients With Chronic Lymphocytic Leukemia (Study #02)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00337519
• Other study ID #: CLL #02
• Secondary ID: DJCLS-R03/01
• Status: Active, not recruiting
• Phase: Phase 2
• First received: June 15, 2006
• Last updated: January 28, 2009
• Start date: January 2003
• Est. completion date: April 2009

Study information

• Verified date: January 2009
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

Patients with advanced chronic lymphocytic leukemia (CLL) have a poor long-term prognosis. Allogeneic stem cell transplantation (SCT) in patients with CLL has only rarely been performed in the past because the clinical outcome after myeloablative conditioning was poor, mainly due to the high treatment-related mortality. However long-term disease-free survival after allogeneic SCT has been reported. Recently it has been demonstrated by our group and others that non-relapse mortality can be reduced significantly with the use of reduced-intensity conditioning regimens. Yet, graft versus host disease (GVHD) remains an important problem in this setting.

Alemtuzumab is an effective drug for the treatment of patients with advanced CLL and has been successfully applied for GVHD-prophylaxis in the setting of myeloablative and reduced-intensity conditioning regimens. The goal of the present study is to evaluate the role of alemtuzumab as part of a fludarabine-based reduced intensity conditioning regimen for allogeneic SCT in patients with advanced CLL.

Description:

Patients with relapsed or refractory CLL who are eligible for the study receive a cytoreductive therapy until SCT. Irrespective to the formal response, patients proceed to allogeneic SCT after fludarabine-based reduced-intensity conditioning. The use of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells > 3 x 10E6 CD34 cells/kg is recommended, but bone marrow > 1 x 10E8 MNC/kg is accepted. GVHD-prophylaxis is based on cyclosporine A adapted to blood levels (150 to 200 ng/mL) over a period of three months. In Phase I of the study, alemtuzumab has been applied as part of the conditioning regimen until day 5. In Phase II, alemtuzumab is given as cytoreductive pre-treatment with the last application of alemtuzumab scheduled for day 14 and after Amendment II in September 2006 scheduled for day 28. Furthermore methotrexate is given on days 1, 3, 6. and 11 at a projected cumulative dose of 45 mg/m2. Subsequent immunosuppressive therapy depends on the occurrence of GvHD, the development of chimerism, and residual disease. Patients with relapsing or residual disease (minimal residual disease excluded) who do not suffer from GvHD should receive donor lymphocytes in increasing dosages. The initial dose is 1 x 105/kg T-cells in unrelated donors and 1 x 106/kg in matched related donors. If no GvHD develops within 6-8 weeks, the next higher dosage is applied.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 82
• Est. completion date: April 2009
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 65 Years

Eligibility

Inclusion Criteria:

• written informed consent

• sufficient organ function

• availability of an HLA-compatible donor (related or unrelated)

• age < 65 years

• karnofsky index > = 70%

• B-CLL requiring treatment after failure of at least one prior cytostatic treatment

Exclusion Criteria:

• positive HIV-serology

• pregnancy

• intolerance to study drugs

• second neoplasia

• serious infections

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Procedure:
• allogeneic stem cell transplantation
see detailed description

Drug:
• Alemtuzumab
alemtuzumab is given as cytoreductive pre-treatment with the last application of alemtuzumab scheduled for day 14

Locations

Country	Name	City	State
Germany	Klinikum Chemnitz gGmbH	Chemnitz
Germany	Uniklinikum Carl Gustav Carus	Dresden
Germany	Deutsche Klinik für Diagnostik GmbH	Wiesbaden

Sponsors (3)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	Deutsche Klinik fuer Diagnostik, University Hospital Carl Gustav Carus

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival		400 days	Yes
Secondary	safety according to common toxicity criteria (CTC)		at discharge and until last follow up	No
Secondary	rate of primary and secondary graft failure		until last follow up	No
Secondary	rate of acute and chronic GVHD		day 100 and last follow up	No
Secondary	response rate		2 years	No
Secondary	chimerism		day 100	No