Rituximab in Preventing Acute Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant for Hematologic Cancer

• Incidence of grades II-IV acute GVHD [ Time Frame: At day 100 ] [ Designated as safety issue: No ]
  Determined with death as a competing risk. Defined and staged using the 1994 consensus conference modifications of the Glucksberg criteria.
  
  

• Event-free survival [ Time Frame: From the date of transplant with relapse/progression or death as censored events, up to 100 days ] [ Designated as safety issue: No ]
  Estimated using Kaplan-Meier estimator.
  
  
• Overall survival [ Time Frame: From the date of transplant with death from any cause as a censored event, up to 100 days ] [ Designated as safety issue: No ]
  Estimated using Kaplan-Meier estimator.
  
  
• Transplant-related mortality (TRM) defined as any mortality after transplantation except mortality from relapsed disease [ Time Frame: At day 100 ] [ Designated as safety issue: No ]
  Reported as a simple percentage.
  
  

PRIMARY OBJECTIVES:

I. To determine the incidence of grade II-IV acute GVHD at day 100 after matched unrelated donor allogeneic hematopoietic cell transplantation (HCT) when incorporating rituximab in the conditioning regimen.

SECONDARY OBJECTIVES:

I. To determine the day 100 transplant related mortality after matched unrelated donor allogeneic HCT when incorporating rituximab in the conditioning regimen.

II. To determine overall survival (OS) and disease-free survival (DFS) after matched unrelated donor allogeneic HCT when incorporating rituximab in the conditioning regimen.

III. To determine the cumulative incidence of infectious complications at day 100 after matched unrelated donor HCT when incorporating rituximab in the conditioning regimen.

IV. To determine the effect of rituximab addition to the conditioning regimen on recovery of T regulatory (T-reg) cells, and to determine the effect of T-cell, including T-reg, number in the stem cell product and at day 30 on the incidence of grade II-IV acute GVHD (aGVHD) and the cumulative infectious complications at day 100.

V. To determine the effect of rituximab addition to the conditioning regimen on antigen presenting myeloid cell recovery, and to determine the effect of dendritic cell subset DC1, DC2 and myeloid-derived suppressor cells (MDSC), number in the stem cell graft and at day +30 on the incidence of acute GVHD grade II-IV and the cumulative incidence of infectious complications at day 100.

OUTLINE:

CONDITIONING REGIMEN: Patients receive one of the following conditioning regimens as per the transplant physician: cyclophosphamide and total-body irradiation (TBI); targeted busulfan and fludarabine; reduced-dose busulfan and fludarabine; or fludarabine and TBI.

GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS: Patients receive rituximab intravenously (IV) on days -6, 1, 8, and 15 and anti-thymocyte globulin IV over 6-8 hours on days -3 to -1. Patients also receive tacrolimus IV continuously and then orally (PO) beginning on day -1 and continuing until day 150 followed by a taper until day 180 and mycophenolate mofetil PO or IV twice daily on days -1 to 60.

TRANSPLANTATION: Patients undergo allogeneic hematopoietic stem cell transplantation on day 0.

Patients are followed up periodically for 100 days after transplant.