Post-transplant Cyclophosphamide and Sirolimus Following Reduced Intensity Conditioning (RIC) Transplant

Study Overview
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Brief Summary
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This trial will evaluate the safety and efficacy of post-transplant Cy and sirolimus following reduced intensity allogeneic SCT. It is hoped that the combination of a reduced intensity preparative regimen with a calcineurin-free GVHD prophylaxis regimen will decrease the risk of acute and chronic GVHD, by both limiting mucosal toxicity and augmenting immune reconstitution, thereby improving the safety of the procedure. The past experience with post-transplant Cy suggests that SCT recipients will attain rapid donor T cell chimerism, which the investigators hope will translate into improved disease control through the well documented graft-versus-malignancy effects of donor T cells.

Official Title
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A Phase II Trial of Post-Transplant Cyclophosphamide and Sirolimus for Graft-versus-host Disease (GVHD) Prophylaxis Following Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation

Conditions
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Hematologic Neoplasms

Intervention / Treatment
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* Procedure: Allogeneic Hematopoietic Stem Cell Transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Availability of a 7/8 or 8/8 (HLA-A, B, C, DR) related or unrelated donor Age 18-75 One of the following high-risk malignancies Chronic Myelogenous Leukemia Acute Myelogenous Leukemia Myelodysplastic Syndrome Myelofibrosis Acute Lymphocytic Leukemia Acute Lymphoblastic Lymphoma Chronic Lymphocytic Leukemia Prolymphocytic Leukemia Low-grade non-Hodgkin's Lymphoma Mantle Cell Lymphoma Hodgkin Lymphoma Myeloma Exclusion Criteria: Poor cardiac function (EF <40%) Poor pulmonary function (FEV1 and FVC <50% predicted) Poor liver function (bilirubin >/= 2 mg/dl not due to hemolysis, Gilbert's or primary malignancy) Poor renal function (creatinine >/= 2 mg/dl or creatinine clearance <40mL/min) Karnofsky status <70% HIV positive

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reduced Intensity Allogeneic Stem Cell Transplantation<br>All patients will receive fludarabine, busulfan and cyclophosphamide as the conditioning regimen prior to an allo SCT. Patients will then receive 2 doses of cyclophosphamide post-transplant and utilize sirolimus and mycophenolate mofetil (in mismatched transplants) as GVHD prophylaxis. | Procedure: Allogeneic Hematopoietic Stem Cell Transplantation<br>* Patients will receive fludarabine, busulfan and cyclophosphamide as the conditioning regimen prior to an allo SCT. Patients will then receive 2 doses of cyclophosphamide post-transplant and utilize sirolimus and mycophenolate mofetil (in mismatched transplants) as GVHD prophylaxis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of GVHD | To estimate the incidence of graft-versus-host disease (GVHD) when utilizing post-transplant cyclophosphamide (Cy) and sirolimus for GVHD prophylaxis following reduced intensity allogeneic hematopoietic stem cell transplantation (SCT) in patients with high risk hematologic malignancies. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Absolute Neutrophil Count (ANC)/Platelet Engraftment | To estimate the incidence of neutrophil and platelet engraftment | Approximately Day 30 | 
| Number of Participants With Non-Relapse Mortality |  | 1 year | 
| Number of Patients With Disease Free Survival at 2 Years |  | 2 years | 
| Number of Patients to Achieve Full Donor Chimerism | Characterize rate of achievement of full donor chimerism | 1 year | 
| Number of Patients With Overall Survival at 2 Years. |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Myelogenous Leukemia, Acute Myelogenous Leukemia, Myelodysplastic Syndrome, Myelofibrosis, Acute Lymphocytic Leukemia, Acute Lymphoblastic Lymphoma, Chronic Lymphocytic Leukemia, Prolymphocytic Leukemia, Low-grade non-Hodgkin's Lymphoma, Mantle Cell Lymphoma, Hodgkin Lymphoma, Myeloma