Prophylactic Transfer of Leukemia-reactive T Cells After Allogeneic Transplantation

NCT ID: NCT00460629

Last Updated: 2013-06-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-03-31

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

Conditions

Chronic Myeloid Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

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

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Carl Gustav Carus

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Martin Bornhäuser, MD

Role: PRINCIPAL_INVESTIGATOR

Medical Clinic, University Hospital Dresden

Locations

Medizinische Klinik und Poliklinik I

Dresden, , Germany

Countries

Germany

References

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 allogeneic hematopoietic cell transplantation. Leukemia. 2006 Nov;20(11):2055-7. doi: 10.1038/sj.leu.2404383. Epub 2006 Aug 31. No abstract available.

Reference Type: RESULT

PMID: 16990776 (View on PubMed)

Bornhauser M, Thiede C, Platzbecker U, Kiani A, Oelschlaegel U, Babatz J, Lehmann D, Holig K, Radke J, Tuve S, Wermke M, Wehner R, Jahnisch H, Bachmann MP, Rieber EP, Schetelig J, Ehninger G, Schmitz M. Prophylactic transfer of BCR-ABL-, PR1-, and WT1-reactive donor T cells after T cell-depleted allogeneic hematopoietic cell transplantation in patients with chronic myeloid leukemia. Blood. 2011 Jun 30;117(26):7174-84. doi: 10.1182/blood-2010-09-308569. Epub 2011 May 3.

Reference Type: DERIVED

PMID: 21540460 (View on PubMed)

Other Identifiers

EK126092000

Identifier Type: -

Identifier Source: org_study_id