Graft-Versus-Host Disease (GVHD) Prophylaxis After Allogeneic Peripheral Blood Hematopoietic Cell Transplantation

Study Overview
=================
Brief Summary
-----------------
The purpose of this research is to compare the effectiveness of Tacrolimus and Rapamycin to Tacrolimus and Methotrexate in the prevention of severe graft-versus-host-disease. Graft-versus-host-disease (GVHD) is a risk associated with allogeneic hematopoietic cell transplants (HCT). An allogeneic hematopoietic cell transplant is a transplant using bone marrow and blood cells that come from someone other than the patient (a donor).

Detailed Description
-----------------
All drugs used in this study have been used in the prevention of graft-versus-host-disease after allogeneic hematopoietic cell transplant. Tacrolimus and Methotrexate used in combination are currently used as standard of care in the prevention of graft-versus-host-disease after allogeneic hematopoietic cell transplant. Tacrolimus and Rapamycin is a newer combination we are testing to see if it would be better than Tacrolimus and Methotrexate.

Official Title
-----------------
Phase II Trial of Tacrolimus and Rapamycin vs. Tacrolimus and Methotrexate as GVHD Prophylaxis After Allogeneic Peripheral Blood Hematopoietic Cell Transplantation

Conditions
-----------------
Acute Graft Versus Host Disease

Intervention / Treatment
-----------------
* Drug: Tacrolimus (TAC)
* Drug: Methotrexate (MTX)
* Drug: Rapamycin (RAPA)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 16 and ≤ 70 Signed informed consent Adequate vital organ function No active infection, or asymptomatic infection well controlled by antibiotic HIV negative by ELISA or RT-PCR [if ELISA is positive and RT-PCR is negative, the ELISA is considered false positive] Hepatitis B and C negative by serology or RT-PCR Performance status: Karnofsky Performance Status Score ≥ 60%. Exclusion Criteria: Those with any Sorror's co-morbidity factors with score > 3 2 or more Sorror's factors with composite score of ≥ 3

Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tacrolimus / Rapamycin (TAC/RAPA)<br>Tacrolimus: beginning 3 days before transplant and given for at least 50 days. Rapamycin: given the day before transplant and continued daily for at least one year. | Drug: Tacrolimus (TAC)<br>* Tacrolimus: administered at 0.02 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3.<br>* Other names: Protopic;Drug: Rapamycin (RAPA)<br>* Rapamycin: initially as 9 mg oral loading dose on day -1. Thereafter, administered as an oral regimen of 4 mg daily.<br>* Other names: Sirolimus;|
| Active Comparator: Tacrolimus / Methotrexate (TAC/MTX)<br>Tacrolimus: beginning 3 days before transplant and given for at least 50 days. Methotrexate: given on days 1, 3, 6 and 11, after transplant. | Drug: Tacrolimus (TAC)<br>* Tacrolimus: administered at 0.02 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3.<br>* Other names: Protopic;Drug: Methotrexate (MTX)<br>* Methotrexate: administered on day 1 at dose of 15 mg/m^2, and a dose of 10 mg/m^2 on days 3, 6, and 11. Dose can be adjusted for reduced creatinine clearance.<br>* Other names: Rheumatrex;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Evidence of Acute Graft Versus Host Disease (aGVHD), Post Transplant | Incidence of acute graft versus host disease grades 2-3 according to the Common Toxicity Criteria (CTC) version 3. Graft-versus-host-disease (GVHD) is a risk associated with allogeneic hematopoietic cell transplants (HCT). Clinical evidence of acute GVHD was recorded per standard grading scheme. Acute GVHD classified as the following: classic acute GVHD - onset within 100 days after transplant persistent - acute GVHD with onset prior to day 100 and without resolution beyond day 100 recurrent - acute GVHD recurrent after prior episode of acute GVHD late acute GVHD - syndrome consistent with acute GVHD, without features of chronic GVHD, with onset occurring beyond 100 days | 100 Days Post Transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Increased Absolute Numbers of Regulatory T Cells (Treg) | Absolute numbers of Treg at designated time points according to study arm. MTX = methotrexate/tacrolimus-treated patients; SIR = sirolimus/tacrolimus-treated patients; Treg absolute number units = number of cells/microL. A two-sided Wilcoxon's rank-sum test was employed to test differences in percent Treg (% Treg/total CD4+ cells). | 30 days and 90 days | 
| 2 Year Post Transplant Overall Survival (OS) Rate | Defined as time from transplantation (day 0 as day of stem cell infusion per standard nomenclature) to death from any cause . | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
GVHD, Acute Graft Versus Host Disease (aGVHD), graft-versus-host disease, tacrolimus, sirolimus, methotrexate, combination therapy, GVHD prophylaxis