Prophylactic Transfer of Leukemia-reactive T Cells After Allogeneic Transplantation

June 19, 2013 updated by: University Hospital Carl Gustav Carus

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

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.

Study Overview

Status

Completed

Conditions

Chronic Myeloid Leukemia

Intervention / Treatment

Procedure: Application of activated donor T 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 Type

Interventional

Enrollment (Anticipated)

Phase

Phase 2
Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Germany
- - Dresden, Germany, 01307
    - Medizinische Klinik und Poliklinik I

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Rate of acute and chronic GvHD Time Frame: 3 years	3 years
Rate of infectious complications Time Frame: 2 years	2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Carl Gustav Carus

Investigators

Principal Investigator: Martin Bornhäuser, MD, Medical Clinic, University Hospital Dresden

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2005

Primary Completion (Actual)

December 1, 2011

Study Registration Dates

First Submitted

April 12, 2007

First Submitted That Met QC Criteria