Stem Cell Transplant for Bone Marrow Failure Syndromes

Diamond-Blackfan Anemia Clinical Trial

Official title:

Bone Marrow Transplantation for Non-Malignant Congenital Bone Marrow Failure Disorders

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00176878
• Other study ID #: MT2000-18
• Secondary ID: 9504M09637
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: September 12, 2005
• Last updated: December 3, 2017
• Start date: June 2000
• Est. completion date: March 2009

Study information

• Verified date: December 2017
• Source: Masonic Cancer Center, University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00005895

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: March 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 35 Years

Eligibility

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

Related Conditions & MeSH terms

• Anemia, Diamond-Blackfan
• Bone Marrow Diseases
• Diamond-Blackfan Anemia
• Exocrine Pancreatic Insufficiency
• Kostmann's Neutropenia
• Neutropenia
• Pancytopenia
• Shwachman-Diamond Syndrome
• Syndrome

Intervention

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.

Drug:
• Fludarabine monophosphate
fludarabine 175 mg/m^2 (total) on Days -6 through -3.

Procedure:
• Total lymphoid irradiation
Dose 500 cGy radiation therapy to specific areas of the body

Drug:
• Busulfan
Busulfan 8 mg/kg (total) on Days - 8 and -7 (orally or through the catheter),

Biological:
• anti-thymocyte globulin
anti-thymocyte globulin (ATG) 15 mg/kg on days -2 and -1 via catheter

Locations

Country	Name	City	State
United States	University of Minnesota Medical Center	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients Alive (Survival) at 2 Years	Calculated from day 1 of transplant to last contact.	2 years
Secondary	Number of Patients Alive at Three Years (Survival)	Number of subjects who survived 3 years post-transplant.	3 years
Secondary	Number of Patients With Succcessful Engraftment After Transplantation	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.	42 Days
Secondary	Number of Patients With Grade 2-4 Acute Graft Versus Host Disease	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.	100 Days
Secondary	Number of Patients With Chronic Graft Versus Host Disease	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.	2 years
Secondary	Number of Patients With Disease Recurrence	Number of patients who exhibited disease recurrence at 2 years.	2 years