Allogeneic Transplantation For Severe Osteopetrosis

Severe Osteopetrosis Clinical Trial

Official title:

Allogeneic Hematopoietic Stem Cell Transplantation For Severe Osteopetrosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00775931
• Other study ID #: MT2008-20
• Secondary ID: 0808M42261
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: August 2008
• Est. completion date: June 2013

Study information

• Verified date: July 2019
• Source: Masonic Cancer Center, University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this research is to explore what we believe may be 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. Prior multi-institutional data in past studies found that approximately 30% of Osteopetrosis patients do not engraft. Therefore, in this study, we utilize a reduced intensity design 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.

Description:

This revised transplant protocol will test the following: 1) the ability to achieve engraftment with the reduced intensity protocol and a second infusion of stem cells on day 42, 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, and evaluation of blood parameters and genes that may be important in the disease process. In older patients, studies to evaluation osteoclast differentiation and function will also be offered.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 45 Years

Eligibility

Inclusion Criteria:

• Patients eligible for transplantation under this protocol will be < or = 45 years of age, and will be diagnosed with severe osteopetrosis. This will be defined as having the following manifestations of the disease.

1. Bones that are uniformly markedly dense based on skeletal survey

2. No history that would suggest autosomal dominant inheritance

3. 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 significantly 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

Related Conditions & MeSH terms

• Osteopetrosis
• Severe Osteopetrosis

Intervention

Procedure:
• umbilical cord blood transplantation
Umbilical cord blood will be collected, processed and shipped according to existing protocols. 2 cord blood units will be utilized if available. The choice of units will be based on the HLA typing standards of the University of Minnesota Blood and Marrow Program. If 2 units are not available, a single unit may be used. If a single unit is used, the unit should provide at least 10 x 107 nucleated cells/kg recipient body weight.

Drug:
• Campath-1H
Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19.

Radiation:
• Total Lymphoid Irradiation
Dose 500 cGy via anteroposterior (AP) and posteroanterior(PA) fields (250 cGy AP and 250 cGy PA).

Drug:
• Cyclophosphamide
Cyclophosphamide (50 mg/kg/dose) will be given IV on day -4, -3, -2 and -1 over 2 hours. The total dose to be given over 4 days is 200 mg/kg for cord blood grafts-receiving patients only.
• Busulfan
patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients.
• Fludarabine monophosphate
Fludarabine (35 mg/m2 daily for 5 days, 175 mg/m2 total) will be administered IV over 30 minutes on days -6, -5, -4, -3, and -2 for donor grafts-receiving patients only.

Procedure:
• marrow graft transplantation
Related donor marrow will be collected, processed and shipped according to existing protocols of the National Marrow Donor Program or other URD registry, with the goal of achieving a cell dose of = 6.0 x 108 nucleated cells/kg. The proportion of cells that are CD34+ will be determined prior to the administration of the graft. This will allow a portion of the graft (2 x 106 CD34+ cells) to be frozen for a subsequent infusion on day +42.

Locations

Country	Name	City	State
United States	University of MInnesota, Fairview	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 Who Achieved Donor Cell Engraftment		Day 100
Secondary	Transplant Related Mortality at 100 Days		day 100
Secondary	Transplant Related Toxicity		Day 100 post transplant
Secondary	Incidence of Grade II - IV Acute Graft-versus-host Disease		by Day 100 after transplant