Conditions: Mucositis Graft-versus-host Disease
Keywords: Tacrolimus Methotrexate Mycophenolate mofetil Mucositis Acute graft-versus-host disease (aGVHD) Engraftment hemolytic/uremic syndrome (HUS) Thrombotic thrombocytopenic purpura (TTP)
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 89
Healthy volunteers: no

Brief summary:
A comparative trial where all patients will receive daily doses of tacrolimus (TAC) until day +60 when tapering will begin, in the absence of graft-versus-host disease (GVHD), and discontinued by day +180. In addition patients will be randomized to methotrexate (MTX) or mycophenolate mofetil (MMF) and again, in the absence of GVHD, a tapering schedule will begin on day +240 and be completed on day +360. Doses will be adjusted to maintain blood levels.

Detailed description:
The randomization for this comparative trial will be stratified by conditioning regimen and, for those patients enrolled on MCC-14178, by busulfan AUC level.

All patients will receive daily doses of TAC beginning day -3 (day 0 being the day of hematopoietic stem cell transplant (HCT)) and will be given until day +60 when tapering will begin in the absence of GVHD. Provided no GVHD develops, TAC should be discontinued by day +180. Doses will be adjusted to maintain blood levels.

In addition to TAC, patients will be randomized to one of the following additional anti-GVHD medications: MTX or MMF beginning day 0 at least 2 hours after the end of the HCT. In the absence of GVHD a tapering schedule will begin on day +240 and be completed on day +360.

Study participants will be extensively monitored as inpatients and then weekly as outpatients. Some tests will be conducted at least twice weekly (blood tests, toxicity data, GVHD and physical exams) one-month post-transplant and during the tapering off periods for up to 2 years.

Arms:
arm 1: Tacrolimus and Mycophenolate arm 2: Tacrolimus and Methotrexate

Interventions: intervention 1: Tac+MTX intervention 2: TAC + MMF
Intervention descriptions: intervention 1: Tacrolimus- 0.03mg/kg/24h IV beginning day-3 Methotrexate- 15mg/m2 IV day +1 then 10mg/m2 IV on days 3, 6, 11 post transplant. intervention 2: Tacrolimus- 0.03 mg/kg/24h as a continuous IV infusion, beginning day -3. Mycophenolate Mofetil- 30 mg/kg/day IV in 2 divided doses (q12 hours) beginning day 0 at least 2 hours after the end of the hematopoietic stem cell transplant

Protocol document: