Reduced Intensity AlloTransplant For Osteopetrosis

University of Minnesota (UMN)

Status and phase

Terminated

Phase 2

Conditions

Osteopetrosis

Treatments

Procedure: Stem Cell or Umbilical Cord Blood Transplantation

Procedure: Total Lymphoid Irradiation

Drug: Campath, Busulfan, Clofarabine

Study type

Interventional

Funder types

Other

Identifiers

NCT00638820

MT2007-06 (Other Identifier)

0704M06581

Details and patient eligibility

About

We believe that hematopoietic stem cell transplantation (HSCT) will help subjects with Osteopetrosis generate functioning osteoclasts, and by so doing assist in the resolution of the abnormal bone architecture, and the anemia and bone marrow failure that is also characteristic of this disease. However, we have found in past studies that approximately 30% of Osteopetrosis patients do not engraft. Therefore, in this study, we plan to use a different combination of pre-transplant drugs to try to make transplants safer for this disease, as well as to provide a second infusion of stem cells in patients with matched related or unrelated donors. The purpose of this research is to find a safer and more effective means of performing stem cell transplantation in patients with Osteopetrosis, using chemotherapy and radiation designed to bring about engraftment and lessen transplant mortality.

Full description

This transplant protocol will test the following: 1) the ability to achieve engraftment with the reduced intensity protocol, 2) the mortality associated with transplant by day 100, 3) patient outcomes, based on differential imaging and biologic evaluations prior to transplantation and at designated points after transplantation (day 100, 6 months, 1, 2 and 5 years). Additional biologic studies will include microarray analysis, Campath levels just prior to the administration of the graft, and establishment of mesenchymal stem cell lines. In older patients, studies to evaluation osteoclast differentiation and function will also be offered.

Enrollment

3 patients

Sex

All

Ages

Under 45 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients eligible for transplantation under this protocol will be <45 years of age, and will be diagnosed with severe osteopetrosis. This will be defined as having the following manifestations of the disease.
Bones that are uniformly markedly dense based on skeletal survey
No history that would suggest autosomal dominant inheritance
Evidence of hematologic changes that are attributed to the underlying disease, including the need for ongoing transfusions, OR
the presence of progressive anemia or thrombocytopenia, OR a white blood cell differential with a predominance of immature forms and evidence of extramedullary hematopoiesis, OR
persistence of serious infectious complications that are thought to be due to the abnormal architecture of the bone that are resistant to surgical and medical interventions.

Exclusion criteria

Patients >45 years of age
Evidence of hepatic failure
pulmonary dysfunction sufficient to substantially increase the risk of transplant
Renal dysfunction with glomerular filtration rate (GFR) <30% of predicted.
Cardiac compromise sufficient to substantially increase the risk of transplantation
Severe, stable neurologic impairment.
Human immunodeficiency virus (HIV) positivity.
Pregnant or lactating females