Hematopoietic stem cell transplantation is an effective treatment for a broad range of hematologic, immune, metabolic and malignant diseases. This Is a high-risk procedure which may be complicated by graft-vs.-host disease, graft rejection, regimen related toxicities and infectious complications. Improved therapeutic strategies are needed to improve the outcome and reduce the toxicities. Graft-vs.-host disease is the major complication limiting the broader application of hematopoietic transplantation and novel, more effective therapy is needed.
Specific Aim : We propose a Phase II Randomized, Multicenter Trial Comparing Standard GVIHD Prophylaxis with Etanercept vs. Pentostatin/ATG in Unrelated Donor HCT. This is a multicenter prospective study to examine two promising approaches for prevention of GVHD, with the pentostatin arm derived from a large phase l/ll study at our center(Parmar, et al 2010) and the etanercept arm developed with collaborators at the University of Michigan. The proposed study will test the hypothesis that the addition of etanercept or pentostatin/ATG to standard GVHD prophylaxis will improve 6-month NRM rates for patients undergoing matched unrelated HCT for the treatment of hematologic malignancies when compared to historical rates from the CIBMTR database with standard of care GVHD prophylaxis. The primary endpoint for this trial will be NRM at 6 months post-transplant. Secondary endpoints are two-year survival from the time of transplant, incidences of neutrophil and platelet engraftment, graft failure, acute graft-versus-host disease (GVHD), chronic GVHD, current immunosuppressive free survival, relapse, infections, and adverse events. Biologic correlates will be assessed to predict development of GVHD and its prognosis. The goal is to identify the most promising regimen for further definitive testing in a future Phase III study. The application is a competitive renewal of the University of Texas- MD Anderson Cancer Center (MDACC) as a Core Clinical Center for Blood and Marrow Transplant-Clinical Trials Network. MDACC is the nation's largest NCI designated Comprehensive Cancer Center, and a leader in clinical and translational research in hematopoietic transplantation. We are committed to the success of the BMT-CTN and continue to be leaders in the organization. We are a major contributor to the development of BMT-CTN studies and active accrue patients to its studies.

Public Health Relevance

Allogeneic stem cell transplantation (SCT) is a potentially curative treatment for a broad range of hematologic, immune metabolic and malignant diseases. Acute graft-versus- host disease (GVHD) is a life threatening complication limiting the broader application of SCT. Novel GVHD prophylaxis regimens are needed. This proposal studies the two promising regimens in a randomized phase II study and will identify biomarkers associated with development of GVHD and its prognosis.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Cooperative Clinical Research--Cooperative Agreements (U10)
Project #
4U10HL069334-16
Application #
9069026
Study Section
Special Emphasis Panel (ZHL1)
Program Officer
Di Fronzo, Nancy L
Project Start
2002-06-05
Project End
2017-06-30
Budget Start
2016-07-01
Budget End
2017-06-30
Support Year
16
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Internal Medicine/Medicine
Type
Hospitals
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030
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Steering Committee Of The Blood And Marrow Transplant Clinical Trials Network (2016) The Blood and Marrow Transplant Clinical Trials Network: An Effective Infrastructure for Addressing Important Issues in Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant 22:1747-1757
Levine, John E; Braun, Thomas M; Harris, Andrew C et al. (2015) A PROGNOSTIC SCORE FOR ACUTE GRAFT-VERSUS-HOST DISEASE BASED ON BIOMARKERS: A MULTICENTER STUDY. Lancet Haematol 2:e21-e29
Devine, Steven M; Owzar, Kouros; Blum, William et al. (2015) Phase II Study of Allogeneic Transplantation for Older Patients With Acute Myeloid Leukemia in First Complete Remission Using a Reduced-Intensity Conditioning Regimen: Results From Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncolo J Clin Oncol 33:4167-75
MacMillan, Margaret L; Robin, Marie; Harris, Andrew C et al. (2015) A refined risk score for acute graft-versus-host disease that predicts response to initial therapy, survival, and transplant-related mortality. Biol Blood Marrow Transplant 21:761-7
Levine, John E; Braun, Thomas M; Harris, Andrew C et al. (2015) A prognostic score for acute graft-versus-host disease based on biomarkers: a multicentre study. Lancet Haematol 2:e21-9
Anderlini, Paolo; Wu, Juan; Gersten, Iris et al. (2015) Cyclophosphamide conditioning in patients with severe aplastic anaemia given unrelated marrow transplantation: a phase 1-2 dose de-escalation study. Lancet Haematol 2:e367-75
Bolaños-Meade, Javier; Logan, Brent R; Alousi, Amin M et al. (2014) Phase 3 clinical trial of steroids/mycophenolate mofetil vs steroids/placebo as therapy for acute GVHD: BMT CTN 0802. Blood 124:3221-7; quiz 3335
Switzer, Galen E; Bruce, Jessica G; Harrington, Donna et al. (2014) Health-related quality of life of bone marrow versus peripheral blood stem cell donors: a prespecified subgroup analysis from a phase III RCT-BMTCTN protocol 0201. Biol Blood Marrow Transplant 20:118-27
Bolaños-Meade, Javier; Wu, Juan; Logan, Brent R et al. (2013) Lymphocyte phenotype during therapy for acute graft-versus-host disease: a brief report from BMT-CTN 0302. Biol Blood Marrow Transplant 19:481-5

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