Prophylactic Transfer of Leukemia-reactive T Cells After Allogeneic Transplantation

Chronic Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00460629
• Other study ID #: EK126092000
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: April 12, 2007
• Last updated: June 19, 2013
• Start date: March 2005

Study information

• Verified date: June 2013
• Source: University Hospital Carl Gustav Carus
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Myeloid Leukemia
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid

Intervention

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

Locations

Country	Name	City	State
Germany	Medizinische Klinik und Poliklinik I	Dresden

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Carl Gustav Carus

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Bornhauser M, Thiede C, Babatz J, Schetelig J, Illmer T, Kiani A, Platzbecker U, Herr W, Rieber EP, Ehninger G, Schmitz M. Infusion of bcr/abl peptide-reactive donor T cells to achieve molecular remission of chronic myeloid leukemia after CD34+ selected a — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility of the infusion of in-vitro activated donor T cells		5 years	Yes
Primary	kinetic of BCR-ABL load after transplantation		5 years	No
Secondary	Rate of acute and chronic GvHD		3 years	Yes
Secondary	Rate of infectious complications		2 years	Yes