Stem Cell Transplant for Bone Marrow Failure Syndromes
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.
Procedure: Stem cell transplant
Drug: Fludarabine monophosphate
Procedure: Total lymphoid irradiation
Biological: anti-thymocyte globulin
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Bone Marrow Transplantation for Non-Malignant Congenital Bone Marrow Failure Disorders|
- Number of Patients Alive (Survival) at 2 Years [ Time Frame: 2 years ] [ Designated as safety issue: No ]Calculated from day 1 of transplant to last contact.
- Number of Patients Alive at Three Years (Survival) [ Time Frame: 3 years ] [ Designated as safety issue: No ]Number of subjects who survived 3 years post-transplant.
- Number of Patients With Succcessful Engraftment After Transplantation [ Time Frame: 42 Days ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: Yes ]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 ] [ Designated as safety issue: Yes ]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 ] [ Designated as safety issue: No ]Number of patients who exhibited disease recurrence at 2 years.
|Study Start Date:||June 2000|
|Study Completion Date:||March 2009|
|Primary Completion Date:||March 2009 (Final data collection date for primary outcome measure)|
Experimental: Bone Marrow Failure Disorders
Patients with Diamond-Blackfan Anemia, Kostmann's Neutropenia, Shwachman-Diamond Syndrome
Procedure: Stem cell transplant
Stem cell transplant on Day 0 - healthy marrow from an unrelated individual. A minimum of 1.0 x 10^9/kg nucleated cells/kg ideal body weight will be collected with a goal of 2.0 x 10^9/kg.
Other Name: BMTDrug: Fludarabine monophosphate
fludarabine 175 mg/m^2 (total) on Days -6 through -3.
Other Name: FludaraProcedure: Total lymphoid irradiation
Dose 500 cGy radiation therapy to specific areas of the body
Other Name: TLIDrug: Busulfan
Busulfan 8 mg/kg (total) on Days - 8 and -7 (orally or through the catheter),
Other Name: BusulfexBiological: anti-thymocyte globulin
anti-thymocyte globulin (ATG) 15 mg/kg on days -2 and -1 via catheter
Other Name: ATG
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.
|United States, Minnesota|
|University of Minnesota Medical Center|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||Paul Orchard, MD||University of Minnesota Medical Center|