Study of Low-Intensity Conditioning for Allogeneic Stem Cell Transplant
The purpose of this study is to determine whether a reduced intensity conditioning regimen for stem cell transplant with donor cells will allow the donor cells to be effective without causing health problems.
Lymphocytic Leukemia, Chronic
Procedure: Reduced intensity conditioning
Procedure: Rapid immunosuppressive taper
Procedure: Prophylactic donor leukocyte infusions
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Trial of Adjuvant Cellular Immunotherapy for High-Risk Hematologic Malignancy After Reduced Intensity Allogeneic Stem Cell Transplantation|
- Percentage of Participants With Acute Graft Versus Host Disease (GVHD) Grades 2-4 [ Time Frame: 100 days ] [ Designated as safety issue: No ]
The primary objective of this study was to establish the rate of acute GVHD following prophylactic cellular immunotherapy after allogeneic hematopoietic stem cell therapy using low intensity conditioning for high-risk hematological malignancies. Glucksberg staging was used for organ grading of GVHD. Clinical GVHD was assessed as follows:
Grade 0: No stage 1-4 of any organ Grade 1: Stage 1-2 rash and no liver or gut involvement Grade 2: Stage 3 rash, or Stage 1 liver involvement, or Stage 1 GI Grade 3: Stage 0-3 skin with Stage 2-3 liver, or Stage 2-4 GI Grade 4: Stage 4 skin rash, or Stage 4 liver involvement
- Percentage of Participants With Progression Free Survival [ Time Frame: two years ] [ Designated as safety issue: No ]
The second primary objective was to determine the percentage of participants with progression free survival following prophylactic cellular immunotherapy after allogeneic hematopoietic stem cell therapy using low intensity conditioning for high-risk hematological malignancies.
We define disease progression as disease recurrence within 180 days of transplant.
- To Evaluate Surrogate Markers of GVHD and Correlate These With Clinical Outcomes During the Above Trial [ Time Frame: one year ] [ Designated as safety issue: Yes ]
|Study Start Date:||April 2003|
|Study Completion Date:||February 2013|
|Primary Completion Date:||November 2010 (Final data collection date for primary outcome measure)|
Experimental: Immunosuppression Taper
Reduced intensity conditioning consisting of Busulfan and Fludarabine(fludarabine 150 mg/m2 IV, busulfan 6 mg/kg IV, total lymphoid irradiation 2 Gy), followed by a rapid immunosuppressive taper of Tacrolimus (0.06 mg/kg q12h, PO, Days -7 to +28), Methotrexate (5 mg/m2, IV, Days +1, +3, +6, +11) and Mycophenolate Mofetil (10 mg/kg every 8 hours, PO, Days -6 to +7).
Procedure: Reduced intensity conditioning
Busulfan and Fludarabine regimenProcedure: Rapid immunosuppressive taper
Taper of Tacrolimus, Methotrexate and Mycophenolate MofetilProcedure: Prophylactic donor leukocyte infusions
If the patient has GVHD overall grade 0-1 or skin grade 1 on day +100, then 5 x 107 CD3+ cells/kg recipient weight are given.
In this research study patients will receive dosages of chemotherapy that are lower than the usual dosages. The study will determine whether a shorter duration of immunosuppression will permit the donor cells to be effective against the cancer without causing more severe GVHD (Graft Versus Host Disease). Also to be determined is whether the patient's cancer can be prevented from relapsing after blood stem cell transplant by using prophylactic treatment, giving a donor leukocyte infusion BEFORE a relapse happens.
In this research study samples of blood and bone marrow will be analyzed. These samples will be examined to study the cellular production of inflammatory cytokine levels in attempt to be able to predict which patients will have complications like GVHD or relapse.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00143845
|United States, Michigan|
|The University of Michigan|
|Ann Arbor, Michigan, United States, 48109|
|Principal Investigator:||John E. Levine, MD, MS||The Univeristy of Michigan|