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

Primary Purpose

Hematologic Neoplasms

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Allogeneic Hematopoietic Stem Cell Transplantation
Sponsored by
Northside Hospital, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hematologic Neoplasms focused on measuring 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

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Northside Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Reduced Intensity Allogeneic Stem Cell Transplantation

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
November 18, 2010
Last Updated
April 9, 2015
Sponsor
Northside Hospital, Inc.
Collaborators
Blood and Marrow Transplant Group of Georgia
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1. Study Identification

Unique Protocol Identification Number
NCT01244906
Brief Title
Post-transplant Cyclophosphamide and Sirolimus Following Reduced Intensity Conditioning (RIC) Transplant
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2015
Overall Recruitment Status
Completed
Study Start Date
December 2010 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Northside Hospital, Inc.
Collaborators
Blood and Marrow Transplant Group of Georgia

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematologic Neoplasms
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
26 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Reduced Intensity Allogeneic Stem Cell Transplantation
Arm Type
Experimental
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Allogeneic Hematopoietic Stem Cell Transplantation
Intervention Description
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 Measure Information:
Title
Incidence of GVHD
Description
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 Outcome Measure Information:
Title
Incidence of Absolute Neutrophil Count (ANC)/Platelet Engraftment
Description
To estimate the incidence of neutrophil and platelet engraftment
Time Frame
Approximately Day 30
Title
Number of Participants With Non-Relapse Mortality
Time Frame
1 year
Title
Number of Patients With Disease Free Survival at 2 Years
Time Frame
2 years
Title
Number of Patients to Achieve Full Donor Chimerism
Description
Characterize rate of achievement of full donor chimerism
Time Frame
1 year
Title
Number of Patients With Overall Survival at 2 Years.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott R Solomon, MD
Organizational Affiliation
Blood and Marrow Transplant Group of Georgia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Northside Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States

12. IPD Sharing Statement

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

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