Prophylactic Transfer of Leukemia-reactive T Cells After Allogeneic Transplantation

Phase 1

Completed

• Conditions: Chronic Myeloid Leukemia

• Registration Number: NCT00460629
• Lead Sponsor: University Hospital Carl Gustav Carus

Brief Summary

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

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

Study Timeline

• Study Start: 2005-03
• Study First Submitted: 2007-04-12
• Study First Submitted QC: 2007-04-12
• Study First Posted: 2007-04-16
• Primary Completion: 2011-12
• Status Verified: 2013-06
• Last Update Submitted: 2013-06-19
• Last Update Posted: 2013-06-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Rate of acute and chronic GvHD	3 years
Rate of infectious complications	2 years

Trial Locations

Locations (1)

Medizinische Klinik und Poliklinik I; 🇩🇪 Dresden, Germany