Stem Cell Transplant for Bone Marrow Failures - Full Text View

Sponsors and Collaborators:	Orchard, Paul J., MD Masonic Cancer Center, University of Minnesota
Information provided by:	University of Minnesota
ClinicalTrials.gov Identifier:	NCT00176878

Purpose

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: Busulfan, fludarabine and anti-thymocyte globulin (ATG) Procedure: Total lymphoid irradiation	Phase II Phase III

Genetics Home Reference related topics: Shwachman-Diamond syndrome

MedlinePlus related topics: Anemia Bone Marrow Transplantation

Drug Information available for: Fludarabine Fludarabine monophosphate Busulfan

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Parallel Assignment, Safety/Efficacy Study
Official Title:	Bone Marrow Transplantation for Non-Malignant Congenital Bone Marrow Failure Disorders

Further study details as provided by University of Minnesota:

Primary Outcome Measures:

Outcome of bone marrow transplantation (BMT), e.g. survival and time to various complications will be analyzed with standard statistical methods [ Time Frame: 10 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To provide the potential for curative therapy of Kostmann's neutropenia, Shwachman's neutropenia, Diamond-Blackfan anemia by unrelated donor (URD) bone marrow or cord blood transplantation [ Time Frame: 10 years ] [ Designated as safety issue: No ]
To evaluate the rate of engraftment after transplantation of non-genotypic identical marrow or cord blood cells using a "non-myeloablative" preparative regimen consisting of busulfan, fludarabine, ATG and irradiation [ Time Frame: 10 years ] [ Designated as safety issue: No ]
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 [ Time Frame: 5 years ] [ Designated as safety issue: No ]
To characterize the pharmacokinetic parameters in patients receiving 2 mg/kg/dose of intravenous (IV) busulfan twice daily [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	16
Study Start Date:	June 2000
Estimated Study Completion Date:	June 2010
Estimated Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Intervention Details:

This approach uses high doses of chemotherapy and irradiation in an attempt to kill the defective bone marrow, and allow it to be replaced by a healthy marrow from an unrelated individual

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

radiation therapy to specific areas of the body

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.

Eligibility

Ages Eligible for Study:	up to 35 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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 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 FVC and FEV <70%; O2 saturation <94%
Renal dysfunction with GFR <30% of predicted.
Cardiac compromise, with left ejection fraction <45%.
Severe, stable neurologic impairment.
HIV positivity.
Pregnant or lactating females

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00176878

Contacts

Contact: Paul Orchard, M.D.

612-626-2961

orcha001@umn.edu

Locations

United States, Minnesota
University of Minnesota Medical Center	Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Paul Orchard, MD 612-626-2961 orcha001@umn.edu

Sponsors and Collaborators

Orchard, Paul J., MD

Masonic Cancer Center, University of Minnesota

Investigators

Principal Investigator:

Paul Orchard, MD

University of Minnesota Medical Center

More Information

Responsible Party:	University of Minnesota ( Paul Orchard, M.D. )
Study ID Numbers:	9504M09637, MT2000-18
Study First Received:	September 12, 2005
Last Updated:	September 12, 2008
ClinicalTrials.gov Identifier:	NCT00176878
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Minnesota:

Stem cell transplant
T-cell depletion
TLI
bone marrow failure disorders

Study placed in the following topic categories:

Hematologic Diseases
Aase syndrome
Anemia
Agranulocytosis
Shwachman-Diamond syndrome
Pancytopenia
Leukocyte Disorders
Fludarabine monophosphate
Granulocytopenia
Shwachman syndrome
Antilymphocyte Serum

Red-Cell Aplasia, Pure
Neutropenia
Genetic Diseases, Inborn
Busulfan
Diamond Blackfan anemia
Anemia, Diamond-Blackfan
Anemia, Aplastic
Fludarabine
Aplastic anemia
Leukopenia
Bone Marrow Diseases

Additional relevant MeSH terms:

Disease
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Immunosuppressive Agents
Pharmacologic Actions

Pathologic Processes
Anemia, Hypoplastic, Congenital
Syndrome
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009