Clinical Trial: Stem Cell Transplant for Bone Marrow Failure Syndromes

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Bone Marrow Transplantation for Non-Malignant Congenital Bone Marrow Failure Disorders

Brief Summary: The researchers hypothesize that it will be possible to perform unrelated bone marrow or cord blood transplants in a safer manner by using less intensive therapy yet still achieve an acceptable level of donor cell engraftment for non-malignant congenital bone marrow failure disorders.

Detailed Summary:

Prior to transplantation, subjects will receive the drugs busulfan (orally or through the catheter), as well as fludarabine and anti-thymocyte globulin (ATG) via the catheter. Busulfan, fludarabine and ATG will be given with Total Lymphoid Irradiation (TLI) to help the new donor bone marrow take and grow after transplantation.

Those patients receiving donor marrow will have the T cells (a type of white blood cell in the donor marrow) removed to lower the risk that the new marrow will react to their body, a condition called Graft-Versus-Host-Disease (GVHD). After bone marrow transplantation, subjects will receive drugs to help prevent GVHD, including cyclosporin and mycophenolate mofetil (MMF).

Blood samples are taken at day 28, day 60, day 100, 1 year and as required by medical status yearly for five years after transplant to evaluate how well the new marrow is growing. A bone marrow biopsy is required at day 21, at day 100 and 1 year.


Sponsor: Masonic Cancer Center, University of Minnesota

Current Primary Outcome: Number of Patients Alive (Survival) at 2 Years [ Time Frame: 2 years ]

Calculated from day 1 of transplant to last contact.


Original Primary Outcome: Outcome of BMT, e.g. survival and time to various complications will be analyzed with standard statistical methods

Current Secondary Outcome:

  • Number of Patients Alive at Three Years (Survival) [ Time Frame: 3 years ]
    Number of subjects who survived 3 years post-transplant.
  • Number of Patients With Succcessful Engraftment After Transplantation [ Time Frame: 42 Days ]
    Number of patients who received non-genotypic identical marrow or cord blood cells using a "non-myeloablative" preparative regimen and exhibited engraftment at Day 42.
  • Number of Patients With Grade 2-4 Acute Graft Versus Host Disease [ Time Frame: 100 Days ]
    Number of patients with Grade 2, 3 and 4 Acute (normally observed within the first 100 days) Graft Versus Host Disease. Acute GVHD is staged as follows: overall grade (skin-liver-gut) with each organ staged individually from a low of 1 to a high of 4. Patients with grade IV GVHD usually have a poor prognosis. Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening.
  • Number of Patients With Chronic Graft Versus Host Disease [ Time Frame: 2 years ]
    Number of patients who exhibited chronic (normally occurs after 100 days) Graft Versus Host Disease at 2 years post transplant. Chronic graft-versus-host-disease, over its long-term course, can also cause damage to the connective tissue and exocrine glands.
  • Number of Patients With Disease Recurrence [ Time Frame: 2 years ]
    Number of patients who exhibited disease recurrence at 2 years.


Original Secondary Outcome:

  • To provide the potential for curative therapy of Kostman's neutropenia, Shwachman's neutropenia, Diamond-Blackfan anemia and severe osteopetrosis by unrelated donor (URD) bone marrow or cord blood transplantation.
  • To evaluate the rate of engraftment after transplantation of non-genotypic identical marrow or cord blood cells using a using a “non-myeloablative” preparative regimen consisting of busulfan, fludarabine, ATG and irradiation.
  • To determine the incidence of acute and chronic graft-versus-host disease (GVHD), disease recurrence and three year survival in patients receiving transplantation with non-genotypic matched marrow or cord blood.
  • To characterize the pharmacokinetic parameters in patients receiving 2 mg/kg/dose of IV busulfan twice daily.


Information By: Masonic Cancer Center, University of Minnesota

Dates:
Date Received: September 12, 2005
Date Started: June 2000
Date Completion:
Last Updated: November 6, 2012
Last Verified: November 2012