Tacrolimus/Sirolimus/Methotrexate vs Tacrolimus/Methotrexate or Cyclosporine/Mycophenolate Mofetil for GVHD Prophylaxis After Reduced Intensity Allogeneic Stem Cell Transplantation for Patients With Lymphoma
Condition: Non-hodgkin Lymphoma; Hodgkin Lymphoma
MeSH terms: Lymphoma
Intervention: Sirolimus; Methotrexate; Tacrolimus; Cyclosporine; MMF
Intervention description: Taken orally for at least 12 months; Given intravenously on the first, third and sixth day after transplant; Taken orally or given intravenously for at least 6 months; Taken orally or given intravenously for at least 6 months; Taken orally for about 2 months
Intervention MeSH terms: Cyclosporine; Sirolimus; Mycophenolic Acid; Methotrexate; Tacrolimus; Cyclosporins
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 139.0
Sex: All
Minimum age: 18 Years
Maximum age: 72 Years
Healthy volunteers: No
Keywords: allogeneic stem cell transplant; reduced intensity conditioning; graft versus host disease; GVHD; RIC transplantation

Summary:

      This trial is comparing whether using a drug called sirolimus for graft versus host disease
      (GVHD) prevention can decrease the chance of the participant's lymphoma relapsing after
      transplantation, compared to using a standard GVHD prevention regimen without sirolimus.
      Since mTOR inhibitors have anti-lymphoma activity, their use after transplantation may lead
      to a decreased risk of relapse and hence better transplantation outcome.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients will be eligible if their primary indication for transplantation is among the
             following: Indolent B-cell non-Hodgkin lymphoma (NHL); Aggressive B-Cell NHL; T-cell
             NHL; or Hodgkin Lymphoma.

          -  Patients must have one of the following combinations of disease status and disease
             histology at the time of enrollment: 1) Patients may be transplanted as part of
             first-line therapy if they have one of the following histologies: CLL with adverse
             cytogenetics, MCL or, T-cell NHL. 2) Patients may be transplanted as part of treatment
             for relapsed or refractory disease without a prior autologous transplantation of they
             have one of the following histologies: Indolent NHL (including CLL/SLL), MCL or T-cell
             NHL. 3) Patients may be transplanted as part of treatment for disease that has
             relapsed or progressed after autologous transplantation if they have any of the
             histologies listed above. Patients may also be enrolled without a prior autologous
             transplantation if they have a contraindication to autologous transplantation, in the
             opinion of the treating clinician. 4) There is no minimal or maximal time interval
             from the patient's last anti-lymphoma therapy and the time of transplantation.

          -  18-72 years of age

          -  Matched related or matched unrelated donor

          -  Donor willing to donate peripheral blood stem cells and meeting institutional criteria
             for stem cell donation. The donor must be medically eligible to donate stem cells
             according to individual transplant center criteria.

        Exclusion Criteria:

          -  Patients with Burkitt lymphoma or DLBCL with a c-myc rearrangement

          -  Karnofsky performance status of less than 70% at the time of registration

          -  Prior allogeneic stem cell transplantation (note that prior autologous stem cell
             transplantation is allowed)

          -  Uncontrolled infection

          -  Serum creatinine 2.0mg/dl or greater

          -  Total bilirubin 2.0mg/dl or greater (unless related to hemolysis or Gilbert's
             syndrome)

          -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 3 times or greater
             than the institutional upper limit of normal

          -  Left ventricular ejection fraction < 30%

          -  Cholesterol > 500mg/dl or triglycerides > 500 mg/dl despite appropriate treatment

          -  Seropositivity for HIV

          -  Pregnancy or breast-feeding (effective contraception must be used during therapy and
             for at least 6 months after the end of immunosuppressive agents)

          -  Prior history of allergy to sirolimus, tacrolimus, cyclosporine, methotrexate or MMF

          -  Concomitant treatment with another investigational drug (unless cleared by study
             chair)