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

Phase 2

Completed

Interventions: Drug: Tacrolimus (TAC)
Drug: Rapamycin (RAPA)
Drug: Methotrexate (MTX)

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Tacrolimus / Rapamycin (TAC/RAPA)	Tacrolimus (TAC)	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.
Tacrolimus / Rapamycin (TAC/RAPA)	Rapamycin (RAPA)	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.
Tacrolimus / Methotrexate (TAC/MTX)	Tacrolimus (TAC)	Tacrolimus: beginning 3 days before transplant and given for at least 50 days. Methotrexate: given on days 1, 3, 6 and 11, after transplant.
Tacrolimus / Methotrexate (TAC/MTX)	Methotrexate (MTX)	Tacrolimus: beginning 3 days before transplant and given for at least 50 days. Methotrexate: given on days 1, 3, 6 and 11, after transplant.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Evidence of Acute Graft Versus Host Disease (aGVHD), Post Transplant	100 Days 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: 1. classic acute GVHD - onset within 100 days after transplant 2. persistent - acute GVHD with onset prior to day 100 and without resolution beyond day 100 3. recurrent - acute GVHD recurrent after prior episode of acute GVHD 4. late acute GVHD - syndrome consistent with acute GVHD, without features of chronic GVHD, with onset occurring beyond 100 days

Secondary Outcome Measures

Name	Time	Method
2 Year Post Transplant Overall Survival (OS) Rate	2 years	Defined as time from transplantation (day 0 as day of stem cell infusion per standard nomenclature) to death from any cause .
Incidence of Increased Absolute Numbers of Regulatory T Cells (Treg)	30 days and 90 days	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).