Prophylactic Transfer of Leukemia-reactive T Cells After Allogeneic Transplantation

Study Overview
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Brief Summary
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Efforts to decrease the risk of GvHD by depleting T cells from the graft in CML patients have been complicated by an increased incidence of leukemia-relapse. Newer protocols using CD34+ selected hematopoietic cells from matched-sibling donors and subsequent infusion of T cells in incremental doses to treat or avoid relapse of disease seem to be more promising. In this study, we try to further optimize this approach by the prophylactic infusion of cytotoxic T cells activated ex-vivo against leukemia-associated/specific antigens using peptide-pulsed dendritic cells.

Detailed Description
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The conditioning protocol contains: Total Body Irradiation 8-12 Gy (4-6 x 2 Gy, a 2 x/die) day -9 to-7 Thiotepa 10 mg/kg (2 x 5 mg/kg) day -5 Fludarabine 200 mg/m2 (5 x 40 mg/m2) day -6 to-2 ATG Fresenius 25 mg/kg (5 x 5 mg/kg) day -6 to-2 Cyclosporine A 1 mg/kg Day -10 to-3 on day 0 CD34+ cells after immunomagnetic selection are infused. > 4 x 10e6/kg CD34 cells/kg are required. On days 28, 56 and 112 after transplantation, cytotoxic T cells generated in-vitro are infused in patients who do not have signs of acute GvHD. Regular follow-up compromises immune monitoring including Tetramer analyses of Peptide-reactive T cells

Official Title
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Specific Cellular Immunotherapy in Patients With Chronic Myeloid Leukemia After Allogeneic Stem Cell Transplantation

Conditions
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Chronic Myeloid Leukemia

Intervention / Treatment
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* Procedure: Application of activated donor T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18-60 Ph+ CML HLA A0201, 0301, 1101, B0801 BCR-ABL b3a2 positive no significant comorbidities resistance or intolerance of imatinib Exclusion Criteria: HIV positive blast crisis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: Application of activated donor T cells|Ex-vivo generated donor T cells stimulated by antigen presenting cells loaded with peptides derived from leukemia-associated antigens|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of the infusion of in-vitro activated donor T cells |  | 5 years | 
| kinetic of BCR-ABL load after transplantation |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of acute and chronic GvHD |  | 3 years | 
| Rate of infectious complications |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adoptive immunotherapy, BCR-ABL reactive T cells, Allogeneic Transplantation