Clinical Trial: Stem Cell Transplant for Hemoglobinopathy

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Allogeneic Hematopoietic Stem Cell Transplant for Patients With High Risk Hemoglobinopathy Using a Preparative Regimen to Achieve Stable Mixed Chimerism

Brief Summary:

This study tests the clinical outcomes of one of two preparative regimens (determined by available donor source) in patients with non-malignant hemoglobinopathies. The researchers hypothesize that these regimens will have a positive effect on post transplant engraftment and the incidence of graft-versus-host-disease.

Regimen A2 has replaced Regimen A in this study. Two patients were treated on Regimen A but did not have evidence of initial engraftment thus triggering the stopping rule for that arm of this study.


Detailed Summary:

Prior to transplantation, subjects will receive either:

Cyclophosphamide, Fludarabine, Campath, Total body irradiation (TBI)

Or

Busulfan, Cyclophosphamide, antithymocyte globulin (ATG), granulocyte colony-stimulating factor (GSCF)

These drugs (and the radiation) are being given to help the new stem cells take and grow. On the day of transplantation, subjects will receive stem cells transfused via intravenous (IV) catheter.

After stem cell transplantation, subjects will be given cyclosporine-A and mycophenolate (MMF)/or Methylprednisone/or Methotrexate to reduce the risk of graft-versus-host disease, the complication that occurs when the donor's stem cells react against the patient.


Sponsor: Masonic Cancer Center, University of Minnesota

Current Primary Outcome: Number of Patients Who Experienced Grade 3-5 Treatment Related Toxicity [ Time Frame: 1 year ]

In general, grade 3 equates to moderate, grade 4 to severe and grade 5 to death.


Original Primary Outcome: Efficacy is defined as continued neutrophil engraftment with at least 10% donor cells by d100.

Current Secondary Outcome:

  • The Incidence of Chimerism at 100 Days [ Time Frame: 100 days ]
    The number of patients whose blood and/or bone marrow contains > 10% donor cells.
  • The Incidence of Chimerism at 6 Months [ Time Frame: 6 months ]
    The number of patients whose blood and/or bone marrow contains > 10% donor cells.
  • The Incidence of Chimerism at 1 Year [ Time Frame: 1 year ]
    The number of patients whose blood and/or bone marrow contains > 10% donor cells.
  • The Incidence of Grade 2-4 Acute Graft Versus Host Disease (Acute GVHD) [ Time Frame: 100 days ]
    The number of patients who experienced grades 2-4 Acute GVHD. Acute GVHD is when the donated bone marrow or peripheral blood stem cells view the recipient's body as foreign, and the donated cells/bone marrow attack the body. Grades 2-4 equate to mild to severe disease. Symptoms typically appear within weeks after transplant.
  • The Incidence of Grade 3-4 Acute Graft Versus Host Disease (Acute GVHD) [ Time Frame: 100 days ]
    The number of patients who experienced grades 3-4 Acute GVHD. Acute GVHD is when the donated bone marrow or peripheral blood stem cells view the recipient's body as foreign, and the donated cells/bone marrow attack the body. IGrades 3-4 equate to moderate to severe disease. Symptoms typically appear within weeks after transplant.
  • The Incidence of Chronic Graft Versus Host Disease (Chronic GVHD) [ Time Frame: 6 months ]
    The number of patients who experienced Chronic GVHD. Chronic GVHD is when the donated bone marrow or peripheral blood stem cells view the recipient's body as foreign, and the donated cells/bone marrow attack the body. Chronic GVHD can appear at any time after allogeneic transplant or several years after transplant.
  • The Incidence of Chronic Graft Versus Host Disease (Chronic GVHD) [ Time Frame: 1 year ]
    The number of patients who experienced Chronic GVHD. Chronic GVHD is when the donated bone marrow or peripheral blood stem cells view the recipient's body as foreign, and the donated cells/bone marrow attack the body. Chronic GVHD can appear at any time after allogeneic transplant or several years after transplant.
  • Change in the Patient's Quality of Life as Compared to the Pre-Transplant Assessment [ Time Frame: pre-transplant ]
    The measure for quality of life used in this study is the Karnofsky Performance Score. The Karnofsky Performance Score runs from 100 to 0, where 100 is "perfect" health and 0 is death.
  • Change in the Patient's Quality of Life as Compared to the Pre-Transplant Assessment [ Time Frame: 1 year ]
    The measure for quality of life used in this study is the Karnofsky Performance Score. The Karnofsky Performance Score runs from 100 to 0, where 100 is "perfect" health and 0 is death.
  • Change in the Patient's Quality of Life as Compared to the Pre-Transplant Assessment [ Time Frame: 2 years ]
    The measure for quality of life used in this study is the Karnofsky Performance Score. The Karnofsky Performance Score runs from 100 to 0, where 100 is "perfect" health and 0 is death.
  • Change in the Patient's Quality of Life as Compared to the Pre-Transplant Assessment [ Time Frame: 5 years ]
    The measure for quality of life used in this study is the Karnofsky Performance Score. The Karnofsky Performance Score runs from 100 to 0, where 100 is "perfect" health and 0 is death.
  • Determine Physical Characteristics and Biologic Effects of Mixed Populations of Donor and Host Red Blood Cells [ Time Frame: During study ]
  • Determine the Concentration of Campath in the Serum [ Time Frame: Day 0 ]
  • Overall Survival [ Time Frame: 100 days ]
    Number of patients alive 100 days after transplant.
  • Overall Survival [ Time Frame: 1 year ]
    Number of patients alive 1 year after transplant.
  • Disease Free Survival [ Time Frame: 100 days ]
    Number of patients alive without disease 100 days after transplant.
  • Disease Free Survival [ Time Frame: 1 year ]
    Number of patients alive without disease 1 year after transplant.


Original Secondary Outcome:

  • Determine the incidence of chimerism at 100 days, 6 months and 1 year.
  • Determine the incidence of grade 2-4 and 3-4 acute GVHD at 100 days.
  • Determine the incidence of chronic GVHD at 6 months and 1 year.
  • Determine the physical characteristics and biologic effects of mixed populations of donor and host red blood cells (RBCs).
  • Compare the quality of life (QOL) at 1, 2 and 5 years with the pre-transplant assessment.
  • Determine overall and disease free survival at 100 days and 1 year.


Information By: Masonic Cancer Center, University of Minnesota

Dates:
Date Received: September 12, 2005
Date Started: June 2002
Date Completion: January 2019
Last Updated: March 28, 2017
Last Verified: March 2017