Sirolimus, Tacrolimus, Anti-Thymocyte Globulin, and Rituximab in Preventing Graft-versus-Host Disease in Patients Undergoing Donor Stem Cell Transplant

• Incidence and severity of aGVHD rate [ Time Frame: For 6 months ] [ Designated as safety issue: No ]
  aGVHD will be estimated using cumulative incidence function; the Glucksberg scale will be used to grade aGVHD.
  
  
• Time to engraftment: ANC and platelet [ Time Frame: For 6 months ] [ Designated as safety issue: No ]
  Defined as failure to achieve neutrophil count > 0.5 X 10^9/L for at least three consecutive days before day 40 post transplant; secondary graft failure is defined as achievement of neutrophil count > 0.5 X 10^9/L for at least three consecutive days and then their persistent drop below 0.5 X 10^9/L with < 5% donor chimerism.
  
  
• SAE and AE related to this immunosuppressive regimen [ Time Frame: For 6 months ] [ Designated as safety issue: Yes ]
  All AEs occurring during this study, whether observed by the physician, nurse, or reported by the patient, will be graded per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.02.
  
  

• cGVHD [ Time Frame: At day 30, 60, 90, 180, and 1 and 2 years post-transplant ] [ Designated as safety issue: Yes ]
  
• Overall and disease-free survival [ Time Frame: At 2 years post-transplant ] [ Designated as safety issue: No ]
  
• Incidence of opportunistic infections [ Time Frame: From day 21 until 100 post transplant, and at days 30, 60, 90, and 180 ] [ Designated as safety issue: Yes ]
  
• Incidence of thrombotic microangiopathy [ Time Frame: For 100 days post-transplant ] [ Designated as safety issue: Yes ]
  
• Biomarkers and immunocorrelative studies for association between incidence of acute and cGVHD and biomarkers [ Time Frame: At 30, 60, 90, and 180 days post-transplant ] [ Designated as safety issue: No ]
  

PRIMARY OBJECTIVES:

I. Incidence and severity of acute GVHD (aGVHD). II. To determine time to engraftment absolute neutrophil count (ANC) (> 0.5 x 10^9/L for 3 consecutive days), and platelet (> 20 X 10^9/L for 3 consecutive days).

III. Safety defined by serious adverse events (SAE) and adverse events (AE) related to this immunosuppressive regimen in the first six months post transplant.

SECONDARY OBJECTIVES:

I. Incidence of chronic GVHD (cVHD) measured within two years after transplant. II. Overall and disease-free survival at two years post hematopoietic cell transplantation (HCT).

III. Incidence of opportunistic infections, defined as infection that occurs in people with weakened immune systems and caused by an organism that does not normally cause disease. These include: fungal infections, pneumocystis carinii pneumonia (PCP), and viral infections (cytomegalovirus [CMV], varicella zoster virus [VZV], herpes simplex virus [HSV], BK virus [BK], Epstein-Barr virus [EBV] including post-transplant lymphoproliferative disorder [PTLD]).

IV. Incidence of thrombotic microangiopathy within 100 days of HCT. V. Immunocorrelative studies: T-cell, B cell, natural-killer (NK) cell, regulatory cell, and allo-reactive T cell quantitation studies, using flow cytometry at 30, 60, 90, and 180 days post transplant.

OUTLINE:

Patients receive rituximab intravenously (IV) over 90 minutes on day -7 and 3, tacrolimus IV continuously or orally (PO) once daily (QD), sirolimus PO QD beginning on day -3 with taper, and anti-thymocyte globulin IV over 6 hours on days -3 to -1.

After completion of study treatment, patients are followed up on days 30, 60, 90, 180 and then 1 and 2 years thereafter.