Stem Cell Transplant for Bone Marrow Failure Syndromes - Full Text View

Sponsor:	Masonic Cancer Center, University of Minnesota
Information provided by:	Masonic Cancer Center, 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: Fludarabine monophosphate Procedure: Total lymphoid irradiation Drug: Busulfan Biological: anti-thymocyte globulin	Phase II Phase III

Study Type:	Interventional
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

Resource links provided by NLM:

Genetics Home Reference related topics: cyclic neutropenia Diamond-Blackfan anemia severe congenital neutropenia Shwachman-Diamond syndrome

MedlinePlus related topics: Anemia Bone Marrow Transplantation

Drug Information available for: Busulfan Fludarabine Fludarabine monophosphate

U.S. FDA Resources

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 ] [ Designated as safety issue: No ]
Calculated from day 1 of transplant to last contact.

Secondary Outcome Measures:

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.

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

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.

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 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

Contacts and Locations

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

Locations

United States, Minnesota
University of Minnesota Medical Center
Minneapolis, Minnesota, United States, 55455

Sponsors and Collaborators

Masonic Cancer Center, University of Minnesota

Investigators

Principal Investigator:

Paul Orchard, MD

University of Minnesota Medical Center

More Information

No publications provided

Responsible Party:	Paul Orchard, M.D., Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:	NCT00176878 History of Changes
Obsolete Identifiers:	NCT00005895
Other Study ID Numbers:	MT2000-18, 9504M09637
Study First Received:	September 12, 2005
Results First Received:	June 18, 2009
Last Updated:	September 30, 2010
Health Authority:	United States: Institutional Review Board

Keywords provided by Masonic Cancer Center, University of Minnesota:

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

Additional relevant MeSH terms:

Anemia
Neutropenia
Pancytopenia
Bone Marrow Diseases
Lipomatosis
Exocrine Pancreatic Insufficiency
Anemia, Diamond-Blackfan
Hematologic Diseases
Agranulocytosis
Leukopenia
Leukocyte Disorders
Skin Diseases
Lipid Metabolism Disorders
Metabolic Diseases
Pancreatic Diseases

Digestive System Diseases
Anemia, Hypoplastic, Congenital
Anemia, Aplastic
Red-Cell Aplasia, Pure
Genetic Diseases, Inborn
Antilymphocyte Serum
Busulfan
Fludarabine monophosphate
Fludarabine
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on February 09, 2012