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

Northside Hospital, Inc.26 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hematologic Neoplasms

Interventions

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: 1 year

Secondary Outcomes

Incidence of Absolute Neutrophil Count (ANC)/Platelet Engraftment

To estimate the incidence of neutrophil and platelet engraftment

Time frame: Approximately Day 30

Number of Participants With Non-Relapse Mortality

Time frame: 1 year

Number of Patients With Disease Free Survival at 2 Years

Time frame: 2 years

Number of Patients to Achieve Full Donor Chimerism

Characterize rate of achievement of full donor chimerism

Time frame: 1 year

Number of Patients With Overall Survival at 2 Years.

Time frame: 2 years

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes