Stem Cell Transplantation for Children Affected With Osteopetrosis

Osteopetrosis Clinical Trial

Official title:

Allogeneic Hematopoietic Stem Cell Transplantation for Children Affected With Malignant Osteopetrosis: A Pilot Study

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00145587
• Other study ID #: OPBMT2
• Status: Terminated
• Phase: N/A
• First received: September 1, 2005
• Last updated: July 26, 2012
• Start date: July 2004
• Est. completion date: February 2009

Study information

• Verified date: January 2011
• Source: St. Jude Children's Research Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Malignant infantile osteopetrosis (MIOP) is a rare fatal genetic disorder that is characterized by the bone's inability to regulate remodeling. The only curative therapy is hematopoietic stem cell transplantation. Stem cells provided from an HLA identical matched sibling donor is the standard of care, but not feasible for the majority of patients. In addition, due to the potentially rapid progression of this disease, the time to identify a suitable HLA matched unrelated donor is not optimal. Therefore this study is designed to test the hypothesis that children with osteopetrosis can properly engraft hematopoietic stem cells that are donated from a partially matched parental donor, or "haploidentical" stem cell donor that are processed on the investigational device, CliniMACS selection system.

Description:

The primary objective of this trial will be answered strictly by those patients enrolled who receive a haploidentical stem cell donor graft.

Patients with a matched sibling donor will be offered participation in this clinical trial and will receive a standard myeloablative conditioning regimen followed by the infusion of an unmanipulated bone marrow graft. However, data from these transplant recipients will be reported in a descriptive manner only.

Secondary Objectives in this trial include the following:

• To describe the outcome of children with MIOP who receive hematopoietic stem cells from a matched sibling donor or a haploidentical donor utilizing a uniform approach one year from transplant

• To estimate the fraction of children with MIOP who have a genetic defect correlating to the osteopetrosis phenotype

• To assess carrier-state of the genetic mutation in parents with an affected child

• To assess carrier-state of the genetic mutation in siblings of affected children

• To estimate the effect of age at the time of hematopoietic stem cell transplantation on the overall outcome of children with MIOP

• To describe the kinetics of select cytokine expression before and after transplantation

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 15
• Est. completion date: February 2009
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Clinical diagnosis of malignant osteopetrosis as documented by bone marrow biopsy and radiographic imaging

• A suitable hematopoietic stem cell donor is available

Exclusion Criteria:

• Participant has the Carbonic Anhydrase II (CAII) deficiency osteopetrosis variant

• Symptomatic cardiac disease or evidence of significant cardiac dysfunction by ECHO (shortening fraction <30%)

• Creatinine clearance = 40ml/min/1.73m^2

• Bilirubin = 3mg/dL

• SGPT = 500 U/L

• Evidence of current severe infection which would preclude ablative chemotherapy or a successful transplantation

• Karnofsky or Lansky score < 70 noting expected abnormalities

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Osteopetrosis

Intervention

Procedure:
• Stem Cell Transplantation
An infusion of HLA partially matched family member donor stem cells processed through the use of the investigational Miltenyi Biotec CliniMACS device.

Device:
• Miltenyi Biotec CliniMACS
Stem cell selection device

Drug:
• Systemic chemotherapy and antibodies
Haploidentical stem cell transplant recipients will receive a reduced intensity conditioning regimen consisting of OKT-3, Fludarabine, Thiotepa , and Melphalan followed by an infusion of a T-cell depleted donor stem cell product. Rituximab will be administered within 24 hours of the infusion in an effort to prevent post transplantation lymphoproliferative disorders (PTLPD). In addition to T-cell depletion of the donor product, cyclosporine will be provided as prophylaxis for (GVHD)Graft versus Host Disease Recipients of a matched sibling donor product will receive a myeloablative conditioning regimen consisting of busulfan and cyclophosphamide. Cyclosporine will be administered for GVHD prophylaxis.

Locations

Country	Name	City	State
United States	St. Jude Children's Research Hospital	Memphis	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
St. Jude Children's Research Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Engraftment	To determine the need for blood or platelet transfusions and the presence of donor cells being present in the transplant recipient's bone marrow or peripheral blood by 100 day after transplantation for children with malignant infantile osteopetrosis who have received a haploidentical stem cell graft.	100 days post-transplant	Yes

External Links

•   St. Jude Children's Research Hospital