Allogeneic Stem Cell Transplantation in Chronic Lymphocytic Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00337519
Recruitment Status : Unknown
Verified January 2009 by Charite University, Berlin, Germany.
Recruitment status was:  Active, not recruiting
First Posted : June 16, 2006
Last Update Posted : January 29, 2009
University Hospital Carl Gustav Carus
Deutsche Klinik fuer Diagnostik
Information provided by:
Charite University, Berlin, Germany

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.

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Procedure: allogeneic stem cell transplantation Drug: Alemtuzumab Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 82 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Chemo-Immunotherapy With Allogeneic Blood Stem Cell Transplantation in Patients With Chronic Lymphocytic Leukemia (Study #02)
Study Start Date : January 2003
Estimated Primary Completion Date : April 2009
Estimated Study Completion Date : April 2009

Arm Intervention/treatment
Experimental: 1
see detailed description
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

Primary Outcome Measures :
  1. Progression-free survival [ Time Frame: 400 days ]

Secondary Outcome Measures :
  1. safety according to common toxicity criteria (CTC) [ Time Frame: at discharge and until last follow up ]
  2. rate of primary and secondary graft failure [ Time Frame: until last follow up ]
  3. rate of acute and chronic GVHD [ Time Frame: day 100 and last follow up ]
  4. response rate [ Time Frame: 2 years ]
  5. chimerism [ Time Frame: day 100 ]

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Ages Eligible for Study:   up to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00337519

Klinikum Chemnitz gGmbH
Chemnitz, Germany, 09113
Uniklinikum Carl Gustav Carus
Dresden, Germany, 01307
Deutsche Klinik für Diagnostik GmbH
Wiesbaden, Germany, 65191
Sponsors and Collaborators
Charite University, Berlin, Germany
University Hospital Carl Gustav Carus
Deutsche Klinik fuer Diagnostik
Study Chair: Johannes Schetelig, MD University Hospital Carl Gustav Carus, Dresden

Responsible Party: Dr. J. Schetelig, University Hospital Carl Gustav Carus Identifier: NCT00337519     History of Changes
Other Study ID Numbers: CLL #02
First Posted: June 16, 2006    Key Record Dates
Last Update Posted: January 29, 2009
Last Verified: January 2009

Keywords provided by Charite University, Berlin, Germany:
chronic lymphocytic leukemia
reduced intensity conditioning
allogeneic stem cell transplantation

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Antineoplastic Agents