Tacrolimus and Mycophenolate Mofetil (MMF) in GVHD Prophylactic Regimen Compared to Tacrolimus and Methotrexate (MTX

Study Overview
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Brief Summary
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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
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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.

Official Title
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Safety of Tacrolimus And Methotrexate (MTX) Versus Tacrolimus And Mycophenolate Mofetil (MMF) As Graft Versus Host Disease Prophylaxis In Allogeneic Hematopoietic Cell Transplants (HCT)

Conditions
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Mucositis, Graft-versus-host Disease

Intervention / Treatment
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* Drug: Tac+MTX
* Drug: TAC + MMF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Patient must be going through a T cell-replete allogeneic transplant Exclusion Criteria: - A contraindication to the use of tacrolimus, mycophenolate, or methotrexate
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: TAC + MMF<br>Tacrolimus and Mycophenolate | Drug: TAC + MMF<br>* 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<br>* Other names: Mycophenolate mofetil, CellCept(R);|
| Other: TAC+MTX<br>Tacrolimus and Methotrexate | Drug: Tac+MTX<br>* 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.<br>* Other names: Methotrexate,;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Severe Mucositis | Mucositis was assessed prospectively daily while the patient was hospitalized and graded retrospectively based on nurse and clinician assessments according to the clinical criteria set forth in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE; version 3.0). Severe mucositis as defined as grade 3 or grade 4. | 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Acute Graft-vs-host Disease (aGVHD) | incidence of aGVHD (grades 2 - 4) 100 days post allogeneic hematopoietic cell transplantation | 100 days post transplant | 
| Overall Survival | number of participants alive at one year | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tacrolimus, Methotrexate, Mycophenolate mofetil, Mucositis, Acute graft-versus-host disease (aGVHD), Engraftment, hemolytic/uremic syndrome (HUS), Thrombotic thrombocytopenic purpura (TTP)