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

Phase 2

Completed

• Conditions: Hematologic Neoplasms
• Interventions: Procedure: Allogeneic Hematopoietic Stem Cell Transplantation

• Registration Number: NCT01244906
• Lead Sponsor: Northside Hospital, Inc.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-11-18
• Study First Submitted QC: 2010-11-18
• Study First Posted: 2010-11-19
• Study Start: 2010-12
• Primary Completion: 2014-04
• Study Completion: 2014-12
• Status Verified: 2015-01
• Results First Submitted: 2015-01-29
• Results First Submitted QC: 2015-03-13
• Results First Posted: 2015-03-17
• Last Update Submitted: 2015-04-09
• Last Update Posted: 2015-05-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Reduced Intensity Allogeneic Stem Cell Transplantation	Allogeneic Hematopoietic Stem Cell Transplantation	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.

Primary Outcome Measures

Name	Time	Method
Incidence of GVHD	1 year	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Northside Hospital; 🇺🇸 Atlanta, Georgia, United States