Allogeneic Stem Cell Transplantation in Chronic Lymphocytic Leukemia

NCT ID: NCT00337519

Last Updated: 2009-01-29

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-01-31
• Study Completion Date: 2009-04-30

Brief 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.

Detailed 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.

Conditions

Chronic Lymphocytic Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

see detailed description

Group Type: EXPERIMENTAL

allogeneic stem cell transplantation

Intervention Type: PROCEDURE

see detailed description

Alemtuzumab

Intervention Type: DRUG

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

Interventions

allogeneic stem cell transplantation

see detailed description

Intervention Type: PROCEDURE

Alemtuzumab

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

Intervention Type: DRUG

Eligibility Criteria

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

• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Carl Gustav Carus

OTHER

Sponsor Role: collaborator

Deutsche Klinik fuer Diagnostik

OTHER

Sponsor Role: collaborator

Charite University, Berlin, Germany

OTHER

Sponsor Role: lead

Responsible Party

University Hospital Carl Gustav Carus

Principal Investigators

Johannes Schetelig, MD

Role: STUDY_CHAIR

University Hospital Carl Gustav Carus, Dresden

Locations

Klinikum Chemnitz gGmbH

Chemnitz, Chemnitz, Germany

Uniklinikum Carl Gustav Carus

Dresden, , Germany

Deutsche Klinik für Diagnostik GmbH

Wiesbaden, , Germany

Countries

Germany

Other Identifiers

DJCLS-R03/01

Identifier Type: -

Identifier Source: secondary_id

CLL #02

Identifier Type: -

Identifier Source: org_study_id