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Trial NCT00000591

Resource URI: http://static.linkedct.org/resource/trials/NCT00000591
linkedct:brief_title T-Cell Depletion in Unrelated Donor Marrow Transplantation
linkedct:condition <http://static.linkedct.org/resource/condition/1780>
linkedct:condition <http://static.linkedct.org/resource/condition/5368>
linkedct:condition <http://static.linkedct.org/resource/condition/6461>
linkedct:condition <http://static.linkedct.org/resource/condition/7212>
linkedct:condition <http://static.linkedct.org/resource/condition/8449>
linkedct:criteria No eligibility criteria
linkedct: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.
linkedct:download_date Information obtained from ClinicalTrials.gov on December 30, 2009
linkedct:eligibility_gender Both
linkedct:eligibility_healthy_volunteers No
linkedct:eligibility_maximum_age 55 Years
linkedct:eligibility_minimum_age 1 Year
linkedct:end_date February 2005
linkedct:enrollment 0 (xsd:int)
linkedct:firstreceived_date October 27, 1999
linkedct:id NCT00000591
rdfs:label Trial NCT00000591
linkedct:lastchanged_date November 10, 2005
linkedct:lead_sponsor_agency National Heart, Lung, and Blood Institute (NHLBI)
linkedct:nct_id NCT00000591
linkedct:number_of_arms 0 (xsd:int)
linkedct:number_of_groups 0 (xsd:int)
linkedct:org_study_id 311
linkedct:overall_official <http://static.linkedct.org/resource/overall_official/29536>
linkedct:overall_official <http://static.linkedct.org/resource/overall_official/54131>
linkedct:overall_status Completed
linkedct:oversight <http://static.linkedct.org/resource/oversight/2918>
foaf:page <http://clinicaltrials.gov/show/NCT00000591>
linkedct:phase Phase 3
linkedct:reference <http://static.linkedct.org/resource/reference/15964>
linkedct:reference <http://static.linkedct.org/resource/reference/1698>
linkedct:reference <http://static.linkedct.org/resource/reference/27163>
linkedct:reference <http://static.linkedct.org/resource/reference/27880>
linkedct:reference <http://static.linkedct.org/resource/reference/27899>
linkedct:reference <http://static.linkedct.org/resource/reference/28268>
linkedct:reference <http://static.linkedct.org/resource/reference/50054>
linkedct:reference <http://static.linkedct.org/resource/reference/50575>
linkedct:reference <http://static.linkedct.org/resource/reference/50819>
linkedct:reference <http://static.linkedct.org/resource/reference/51615>
linkedct:reference <http://static.linkedct.org/resource/reference/51827>
linkedct:reference <http://static.linkedct.org/resource/reference/53966>
linkedct:source National Heart, Lung, and Blood Institute (NHLBI)
linkedct:start_date November 1993
linkedct:study_design Treatment, Randomized
linkedct:study_type Interventional
linkedct:summary 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.
rdf:type linkedct:trials
linkedct:verification_date November 2005