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Stem Cell Transplant for Bone Marrow Failure Syndromes

This study has been completed.
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota Identifier:
First received: September 12, 2005
Last updated: November 6, 2012
Last verified: November 2012
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.

Condition Intervention Phase
Diamond-Blackfan Anemia
Kostmann's Neutropenia
Shwachman-Diamond Syndrome
Procedure: Stem cell transplant
Drug: Fludarabine monophosphate
Procedure: Total lymphoid irradiation
Drug: Busulfan
Biological: anti-thymocyte globulin
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Bone Marrow Transplantation for Non-Malignant Congenital Bone Marrow Failure Disorders

Resource links provided by NLM:

Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Number of Patients Alive (Survival) at 2 Years [ Time Frame: 2 years ]
    Calculated from day 1 of transplant to last contact.

Secondary Outcome Measures:
  • 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.

Enrollment: 10
Study Start Date: June 2000
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: BMT
Drug: Fludarabine monophosphate
fludarabine 175 mg/m^2 (total) on Days -6 through -3.
Other Name: Fludara
Procedure: Total lymphoid irradiation
Dose 500 cGy radiation therapy to specific areas of the body
Other Name: TLI
Drug: Busulfan
Busulfan 8 mg/kg (total) on Days - 8 and -7 (orally or through the catheter),
Other Name: Busulfex
Biological: anti-thymocyte globulin
anti-thymocyte globulin (ATG) 15 mg/kg on days -2 and -1 via catheter
Other Name: ATG

Detailed Description:

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.


Ages Eligible for Study:   up to 35 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients eligible for transplantation under this protocol will be <35 years of age, and will be diagnosed with:

    • a bone marrow failure syndrome unresponsive to available therapy, including but not limited to Diamond-Blackfan anemia, Shwachman Diamond syndrome or Kostmann's neutropenia but exclusive of aplastic anemia.
  • Diamond Blackfan Anemia:

    • Patients must show evidence of steroid resistance requiring equivalent of >6 transfusions yearly despite steroid therapy.
    • Evidence of developing aplasia or myelodysplasia will also be criteria for transplantation.
  • Kostmann's Neutropenia, Shwachman-Diamond syndrome:

    • Patients must have been previously diagnosed as having a clinical picture characteristic of Shwachman-Diamond syndrome (exocrine pancreatic insufficiency, growth retardation, metaphyseal dysostosis, neutropenia), or must have a bone marrow aspirate consistent with Kostmann's neutropenia, with no evidence of acute leukemia.
    • Patients must have failed therapy with granulocyte-colony stimulating factor (G-CSF), as determined by an inability to maintain an absolute neutrophil count (ANC) >750 cells/ml(3), or manifesting recurrent infections despite G-CSF administration resulting in life threatening infections or repeated hospitalizations (<4 /year).

Exclusion Criteria:

  • Patients >35 years of age
  • Karnofsky score <70%
  • Hepatic dysfunction as determined by bilirubin >3.0, ALT >150, or active hepatitis
  • Pulmonary function tests with forced volume vital capacity (FVC) and forced expiratory volume (FEV) <70%; O2 saturation <94%
  • Renal dysfunction with glomerular filtration rate (GFR) <30% of predicted.
  • Cardiac compromise, with left ejection fraction <45%.
  • Severe, stable neurologic impairment.
  • Human immunodeficiency virus (HIV) positivity.
  • Pregnant or lactating females
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Please refer to this study by its identifier: NCT00176878

United States, Minnesota
University of Minnesota Medical Center
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Principal Investigator: Paul Orchard, MD University of Minnesota Medical Center
  More Information

Responsible Party: Masonic Cancer Center, University of Minnesota Identifier: NCT00176878     History of Changes
Obsolete Identifiers: NCT00005895
Other Study ID Numbers: MT2000-18
9504M09637 ( Other Identifier: IRB, University of Minnesota )
Study First Received: September 12, 2005
Results First Received: June 18, 2009
Last Updated: November 6, 2012

Keywords provided by Masonic Cancer Center, University of Minnesota:
Stem cell transplant
T-cell depletion
bone marrow failure disorders

Additional relevant MeSH terms:
Bone Marrow Diseases
Exocrine Pancreatic Insufficiency
Anemia, Diamond-Blackfan
Pathologic Processes
Leukocyte Disorders
Hematologic Diseases
Skin Diseases
Lipid Metabolism Disorders
Metabolic Diseases
Pancreatic Diseases
Digestive System Diseases
Anemia, Hypoplastic, Congenital
Anemia, Aplastic
Red-Cell Aplasia, Pure
Genetic Diseases, Inborn
Fludarabine phosphate
Antilymphocyte Serum
Antineoplastic Agents
Antimetabolites, Antineoplastic processed this record on April 26, 2017