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Allogeneic Stem Cell Transplantation Following Chemotherapy in Patients With Hemoglobinopathies

This study has been completed.
Sponsor:
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
Information provided by (Responsible Party):
Catherine Wu, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00153985
First received: September 8, 2005
Last updated: February 6, 2013
Last verified: January 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
Hemoglobinopathies
Sickle Cell Disease
Thalassemia
 Drug: Busulfex
Drug: Fludarabine
Drug: Alemtuzumab
Procedure: Stem Cell Transfusion
 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multi-Center Study Using Allogeneic Stem Cell Transplantation Following Reduced Intensity Chemotherapy in Patients With Hemoglobinopathies

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Stable Engraftment With Donor Stem Cells in Patients With Severe Hemoglobinopathy. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    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. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Outcome was measured by incidence and severity of acute and chronic GVHD following donor stem cell infusion.


Enrollment: 2
Study Start Date: March 2004
Study Completion Date: July 2009
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Busulfex
    Given once daily for 4 days
    Drug: Fludarabine
    Given intravenously once daily for 4 days
    Drug: Alemtuzumab
    One day before fludarabine and busulfex are started, alemtuzumab will be given once daily for 5 days.
    Other Name: CAMPATH
    Procedure: Stem Cell Transfusion
    Performed three days after the end of chemotherapy
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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00153985

Locations
United States, Georgia
Winship Cancer Institute-Emory University
Atlanta, Georgia, United States, 30322
United States, Louisiana
Feist-Weiller Cancer Center-LSU
Shreveport, Louisiana, United States, 71130
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02115
United States, Ohio
Ohio State University College of Medicine
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Dana-Farber Cancer Institute
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
Investigators
Principal Investigator: Catherine J. Wu, MD Dana-Farber Cancer Institute
  More Information

Publications:

Responsible Party: Catherine Wu, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00153985     History of Changes
Other Study ID Numbers: 03-338
Study First Received: September 8, 2005
Results First Received: December 5, 2012
Last Updated: February 6, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:
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

Additional relevant MeSH terms:
Anemia, Sickle Cell
Hemoglobinopathies
Thalassemia
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Genetic Diseases, Inborn
Busulfan
Fludarabine monophosphate
Campath 1G
Fludarabine
Alemtuzumab
 Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on May 16, 2013