Clinical trial NCT00928018
Conditions: Non-hodgkin Lymphoma Hodgkin Lymphoma
Keywords: allogeneic stem cell transplant reduced intensity conditioning graft versus host disease GVHD RIC transplantation
Sponsor: Dana-Farber Cancer Institute
Start date: 2009-06-01; Completion date: 2014-11-01
Enrollment: 139 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.

Detailed description:
* Because no one knows which of the study options is best, participants will be "randomized" into one of the two possible groups for GVHD prophylaxis: 1) a sirolimus-containing regimen (tacrolimus, sirolimus and methotrexate) or 2) a sirolimus-free regimen (tacrolimus and methotrexate or cyclosporine and mycophenolate mofetil).
* Participants will receive a reduced intensity conditioning regimen. This is done to prepare the body for transplantation. This will consist of a combination of drugs (either fludarabine and busulfan or fludarabine, cyclophosphamide and low-dose total body irradiation). The purpose of these drugs is to weaken the immune system and lower the chance of the body rejecting the donated stem cells.
* Participants will also receive the GVHD prophylaxis regimen that they have been randomized to. These drugs will lower the chance of rejecting the donor cells and lower the chance of developing GVHD.

Arms: arm 1: The Sirolimus containing arm will consist of the following drugs:

Experimental Arm: tacrolimus + sirolimus + low-dose methotrexate

Tacrolimus: Administered orally at a dose of 0.05 mg/kg based on ABW bid starting on day -3.

Sirolimus:Given as a loading oral dose of 12 mg on day -3, then as a daily maintenance dose of 4 mg starting on day -2.

Methotrexate: Administered by intravenous bolus infusion, per institutional standard, at a dose of 5 mg/m2 on days +1, +3 and +6. arm 2: There are two choices for the Sirolimus free arm:

Control Arm 1: tacrolimus + methotrexate

Tacrolimus:Administered orally at a dose of 0.05 mg/kg based on ABW bid starting on day -3.

Methotrexate:Administered by intravenous bolus infusion at a dose of 5 mg/m2 on days +1, +3 and +6. For patients receiving stem cells from unrelated donors, an additional dose will be given on day +11.

Control Arm 2: cyclosporine + MMF

Cyclosporine: administered orally at a dose of 6 mg/kg based on ABW bid starting on day -3.

MMF:administered at a dose of 3gm daily orally (or intravenously if the patient cannot tolerate oral administration) divided in 2 or 3 doses (bid or tid) depending on physician preference starting on day 3.
Interventions: intervention 1: Sirolimus intervention 2: Methotrexate intervention 3: Tacrolimus intervention 4: Cyclosporine intervention 5: MMF
Intervention descriptions: intervention 1: Taken orally for at least 12 months intervention 2: Given intravenously on the first, third and sixth day after transplant intervention 3: Taken orally or given intravenously for at least 6 months intervention 4: Taken orally or given intravenously for at least 6 months intervention 5: Taken orally for about 2 months

Protocol documents: