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Allogeneic Stem Cell Transplantation Following Chemotherapy in Patients With Hemoglobinopathies

Primary Purpose

Hemoglobinopathies, Sickle Cell Disease, Thalassemia

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Busulfex
Fludarabine
Alemtuzumab
Stem Cell Transfusion
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemoglobinopathies focused on measuring Hemoglobinopathies, Sickle cell anemia, sickle cell-hemoglobin C disease, sickle cell-B-thalassemia, transfusion-dependant thalassemia, allogeneic transplant, nonmyeloablative transplant, Stem cell transfusion, graft vs. host disease

Eligibility Criteria

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

Inclusion Criteria: Patients with sickle cell disease should have one or more of the following: acute chest syndrome requiring hospitalization; nonhemorrhagic stroke or central nervous system event lasting longer than 24 hours; recurrent caso-occlusive pain or recurrent priapism; sickle neuropathy; bilateral proliferative retinopathy and major visual impairment of at least one eye; osteonecrosis of multiple joints; transfusion dependence; vaso-occlusive. Patients with thalassemia should have one or more of the following: transfusion dependence; iron overload; presence of 2 or more alloantibodies against red cell antigens. Exclusion Criteria: Pregnancy Acute hepatitis Cardiac ejection fraction < 30% Severe renal impairment Severe residual functional neurologic impairment Evidence of HIV infection

Sites / Locations

  • Winship Cancer Institute-Emory University
  • Feist-Weiller Cancer Center-LSU
  • Beth Israel Deaconess Medical Center
  • Dana-Farber Cancer Institute
  • Massachusetts General Hospital
  • Ohio State University College of Medicine

Outcomes

Primary Outcome Measures

Stable Engraftment With Donor Stem Cells in Patients With Severe Hemoglobinopathy.
Outcome was measured by ANC >500 for three consecutive days prior to day 30 after PBSC infusion, >25% of hematopoietic cells are donor derived as determined by molecular chimerism assays or cytogenetic methods prior to day 45 after PBSC infusion and >25% of hematopoietic cells are donor derived as determined by molecular chimerism assays or cytogenetic methods after day 180 after PBSC infusion.

Secondary Outcome Measures

Solid Organ Toxicity Related to the Conditioning Regimen.
Outcome was measured by the assessment of organ toxicity related to Busulfex, fludarabine and alemtuzumab.
The Incidence of Grade II-IV Acute Graft vs. Host Disease.
Outcome was measured by incidence and severity of acute and chronic GVHD following donor stem cell infusion.

Full Information

First Posted
September 8, 2005
Last Updated
July 24, 2013
Sponsor
Dana-Farber Cancer Institute
Collaborators
Beth Israel Deaconess Medical Center, Massachusetts General Hospital, Brigham and Women's Hospital, Emory University, Feist-Weiller Cancer Center at Louisiana State University Health Sciences, Ohio State University
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1. Study Identification

Unique Protocol Identification Number
NCT00153985
Brief Title
Allogeneic Stem Cell Transplantation Following Chemotherapy in Patients With Hemoglobinopathies
Official Title
Multi-Center Study Using Allogeneic Stem Cell Transplantation Following Reduced Intensity Chemotherapy in Patients With Hemoglobinopathies
Study Type
Interventional

2. Study Status

Record Verification Date
July 2013
Overall Recruitment Status
Completed
Study Start Date
March 2004 (undefined)
Primary Completion Date
March 2008 (Actual)
Study Completion Date
July 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute
Collaborators
Beth Israel Deaconess Medical Center, Massachusetts General Hospital, Brigham and Women's Hospital, Emory University, Feist-Weiller Cancer Center at Louisiana State University Health Sciences, Ohio State University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to determine if treatment with reduced-dose busulfex, fludarabine and alemtuzumab (CAMPATH) followed by sten cell infusion will allow for donor stem cells to grow in patients with hemoglobinopathies bone marrow and restore circulating blood counts. In addition the incidence and severity of side effects and of graft vs. host disease (GVHD) will be monitored.
Detailed Description
In order to undergo transplant procedure, patients will be admitted to the hospital for approximately 10-14 days. To prepare patient's bone marrow to accept donor stem cells, they will receive fludarabine and busulfex. Fludarabine will be given intravenously once daily for 4 days. Busulfex will be given once daily for the same 4 days. One day before patients receive busulfex and fludarabine, they will also be given alemtuzumab intravenously once daily for 5 days. Three days after the end of chemotherapy, patients will receive the infusion of donor stem cells. If patients have thalassemia, they will receive subcutaneous injections of filgrastim starting on day one after the donor stem cell transfusion and will continue receiving filgrastim every day until it appears that the donor stem cells have been accepted. If the patient has sickle cell disease, filgrastim will not be given, Additional drugs will be given to help prevent infection (i.e. antibiotics). After stem cell infusion patients will be examined and have blood tests weekly for 1 month. Bone marrow biopsies, and blood work will also be performed 1 month, 3 months, 6 months and 1 year after stem cell infusion. Patients will be on the study for about 12 months. After study is completed progress will be monitored on an annual basis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemoglobinopathies, Sickle Cell Disease, Thalassemia
Keywords
Hemoglobinopathies, Sickle cell anemia, sickle cell-hemoglobin C disease, sickle cell-B-thalassemia, transfusion-dependant thalassemia, allogeneic transplant, nonmyeloablative transplant, Stem cell transfusion, graft vs. host disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Busulfex
Intervention Description
Given once daily for 4 days
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Given intravenously once daily for 4 days
Intervention Type
Drug
Intervention Name(s)
Alemtuzumab
Other Intervention Name(s)
CAMPATH
Intervention Description
One day before fludarabine and busulfex are started, alemtuzumab will be given once daily for 5 days.
Intervention Type
Procedure
Intervention Name(s)
Stem Cell Transfusion
Intervention Description
Performed three days after the end of chemotherapy
Primary Outcome Measure Information:
Title
Stable Engraftment With Donor Stem Cells in Patients With Severe Hemoglobinopathy.
Description
Outcome was measured by ANC >500 for three consecutive days prior to day 30 after PBSC infusion, >25% of hematopoietic cells are donor derived as determined by molecular chimerism assays or cytogenetic methods prior to day 45 after PBSC infusion and >25% of hematopoietic cells are donor derived as determined by molecular chimerism assays or cytogenetic methods after day 180 after PBSC infusion.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Solid Organ Toxicity Related to the Conditioning Regimen.
Description
Outcome was measured by the assessment of organ toxicity related to Busulfex, fludarabine and alemtuzumab.
Time Frame
3 years
Title
The Incidence of Grade II-IV Acute Graft vs. Host Disease.
Description
Outcome was measured by incidence and severity of acute and chronic GVHD following donor stem cell infusion.
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with sickle cell disease should have one or more of the following: acute chest syndrome requiring hospitalization; nonhemorrhagic stroke or central nervous system event lasting longer than 24 hours; recurrent caso-occlusive pain or recurrent priapism; sickle neuropathy; bilateral proliferative retinopathy and major visual impairment of at least one eye; osteonecrosis of multiple joints; transfusion dependence; vaso-occlusive. Patients with thalassemia should have one or more of the following: transfusion dependence; iron overload; presence of 2 or more alloantibodies against red cell antigens. Exclusion Criteria: Pregnancy Acute hepatitis Cardiac ejection fraction < 30% Severe renal impairment Severe residual functional neurologic impairment Evidence of HIV infection
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Catherine J. Wu, MD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Winship Cancer Institute-Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Feist-Weiller Cancer Center-LSU
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71130
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Ohio State University College of Medicine
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
18550258
Citation
Armistead PM, Mohseni M, Gerwin R, Walsh EC, Iravani M, Chahardouli B, Rostami S, Zhang W, Neuberg D, Rioux J, Ghavamzadeh A, Ritz J, Antin JH, Wu CJ. Erythroid-lineage-specific engraftment in patients with severe hemoglobinopathy following allogeneic hematopoietic stem cell transplantation. Exp Hematol. 2008 Sep;36(9):1205-15. doi: 10.1016/j.exphem.2008.04.004. Epub 2008 Jun 11.
Results Reference
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Learn more about this trial

Allogeneic Stem Cell Transplantation Following Chemotherapy in Patients With Hemoglobinopathies

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