Clinical trial NCT00460629: Prophylactic Transfer of Leukemia-reactive T Cells After Allogeneic Transplantation
Official title: Specific Cellular Immunotherapy in Patients With Chronic Myeloid Leukemia After Allogeneic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Chronic Myeloid Leukemia
Keywords: Adoptive immunotherapy
BCR-ABL reactive T cells
Allogeneic Transplantation
Lead sponsor: University Hospital Carl Gustav Carus
Sponsor class: OTHER
First posted: 2007-04-16
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Feasibility of the infusion of in-vitro activated donor T cells
timeFrame: 5 years
measure: kinetic of BCR-ABL load after transplantation
timeFrame: 5 years
Secondary outcomes:
measure: Rate of acute and chronic GvHD
timeFrame: 3 years
measure: Rate of infectious complications
timeFrame: 2 years
Other outcomes:
Locations:
city: Dresden
country: Germany
facility: Medizinische Klinik und Poliklinik I
Study officials:
affiliation: Medical Clinic, University Hospital Dresden
name: Martin Bornhäuser, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.