Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III, Phase II Supportive care, Treatment Active 35 and under Other 9504M09637 MT2000-18, NCT00176878

Trial Description

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.

Further Study Information

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 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

Trial Contact Information

Trial Lead Organizations/Sponsors

Orchard, Paul J., MD

Paul Orchard, MD

Principal Investigator

Paul Orchard, M.D.		Ph: 612-626-2961
		Email: orcha001@umn.edu

U.S.A.
Minnesota
	Minneapolis
	Masonic Cancer Center at University of Minnesota
		Paul Orchard, MD	Ph: 612-626-2961
			Email: orcha001@umn.edu

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00176878
Information obtained from ClinicalTrials.gov on September 16, 2008