T-Cell Depletion in Unrelated Donor Marrow Transplantation

April 14, 2016 updated by: National Heart, Lung, and Blood Institute (NHLBI)
To determine if a reduction in morbidity and mortality from acute and chronic graft versus host disease (GvHD) can be achieved through use of T-cell depletion techniques without a counterbalancing increase in relapse of leukemia in patients receiving an unrelated donor marrow transplant.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

BACKGROUND:

Allogeneic bone marrow transplantation is an accepted therapeutic option for many hematologic, immunologic, and malignant diseases, including chronic myelocytic leukemia and acute leukemia during or after first relapse (second remission). In order to maximize the chance for a successful transplant, it is desirable that the donor and the recipient share the same Human Leukocyte Antigen (HLA) histocompatibility antigens. Because of the Mendelian inheritance of HLA antigens, the chances of finding a match are much greater among relatives than in the general population. However, only about 30 percent of patients needing a transplant have a matched sibling. Thus a transplant from an HLA-matched unrelated donor may be an important alternative for these patients.

Graft versus host disease is a frequent and severe complication of marrow transplantation. Acute GvHD typically occurs within three months after transplantation and is characterized by skin rash, liver dysfunction, and diarrhea. Although the pathophysiology of this disease is not fully defined in humans, data from animal studies suggest that it is mediated by mature donor T cells that react against disparate recipient histocompatibility antigens.

One treatment modality that ameliorates or prevents GvHD following allogeneic marrow transplantation is T cell-depletion of donor marrow before infusion into the recipient. T cell-depletion can be divided into physical methods such as separation by elutriation or sheep cell rosetting, and immunologic methods which use a T cell-specific antibody(ies) plus complement or toxin to kill the cells. These different techniques may remove a subpopulation of T cells, all T cells, or T cells plus other cell types such as B cells or natural killer (NK) cells. The number of stem cells transferred may also be affected.

Unfortunately, in many of the published studies conducted in patients receiving transplants from HLA-matched siblings, T cell-depletion used to prevent or treat GvHD increased the chances of other complications, namely graft failure and leukemia relapse. This is not surprising in light of studies of patients with both early and advanced leukemias that demonstrated a decreased risk of relapse associated with acute and/or chronic GvHD. Because the net effect of these opposing consequences of T cell-depletion on leukemia-free survival in related donor transplants is generally unfavorable, T cell-depletion for related donor marrow transplantation is controversial. The utility of T-cell depletion in unrelated-donor transplants needs to be determined.

The initiative grew out of increasing concern on the part of Institute staff, the bone marrow transplantation community, and members of Congress that graft versus host disease is so frequent and severe a complication of unrelated donor transplants that it has become a limiting factor in their outcome. The initiative was given concept clearance by the May 1992 National Heart, Lung, and Blood Advisory Council and released in January 1993.

DESIGN NARRATIVE:

The primary endpoint of this trial was disease free survival at three years post transplant. Secondary endpoints included overall survival, incidence of GvHD, graft failure, infections and other complications, and time to disease relapse. The covariates considered included age of recipient, disease risk status, interval between diagnosis and transplant, disease type, age and gender of donor, post-transplant chimerism, pre-transplant Karnofsky score, and other measures of performance status. An economic analysis was performed.

Patients were randomly assigned to receive either a T-cell depleted or a non-depleted transplant. Two methods of T-cell depletion were in use: an anti-CD3 monoclonal antibody, T10B9, plus complement, or counterflow elutriation plus the Ceprate column. Each method of T-depletion was part of a package that included a specific pre-transplant conditioning regimen and additional GvHD prophylaxis. Patients randomized to the non-T-cell depleted arm received a conditioning regimen containing cyclophosphamide and total body irradiation, and a GvHD prophylaxis regimen of cyclosporin and methotrexate. A total of 410 patients were enrolled. Enrollment ended October 31, 2000.

A total of 14 transplant centers participated in the study, Follow-up ended in April 2002.

Study Type

Interventional

Phase

  • Phase 3

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

1 year to 55 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

No eligibility criteria

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: Randomized

Collaborators and Investigators

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

Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

  • Shelly Carter, The Emmes Company, LLC
  • John Wagner, University of Minnesota

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

November 1, 1993

Study Completion

February 1, 2005

Study Registration Dates

First Submitted

October 27, 1999

First Submitted That Met QC Criteria

October 27, 1999

First Posted (Estimate)

October 28, 1999

Study Record Updates

Last Update Posted (Estimate)

April 15, 2016

Last Update Submitted That Met QC Criteria

April 14, 2016

Last Verified

November 1, 2005

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 311

Plan for Individual participant data (IPD)

Study Data/Documents

  1. Individual Participant Data Set
    Information identifier: TCD
    Information comments: NHLBI provides controlled access to IPD through BioLINCC. Access requires registration, evidence of local IRB approval or certification of exemption from IRB review, and completion of a data use agreement.
  2. Study Forms

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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