Stem Cell Transplantation for Children Affected With Osteopetrosis

NCT ID: NCT00145587

Last Updated: 2017-05-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-07-31
• Study Completion Date: 2009-02-28

Brief 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.

Detailed 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

Conditions

Osteopetrosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Group Type: OTHER

Stem Cell Transplantation

Intervention Type: PROCEDURE

An infusion of HLA partially matched family member donor stem cells processed through the use of the investigational Miltenyi Biotec CliniMACS device.

Miltenyi Biotec CliniMACS

Intervention Type: DEVICE

Stem cell selection device

Systemic chemotherapy and antibodies

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: PROCEDURE

Miltenyi Biotec CliniMACS

Stem cell selection device

Intervention Type: DEVICE

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.

Intervention Type: DRUG

Other Intervention Names

Haploidentical stem cell transplant; Allogeneic stem cell transplant; T-cell depletion; Transplantation for Osteopetrosis

Eligibility Criteria

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Jude Children's Research Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kimberly A Kasow, DO

Role: PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Locations

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Countries

United States

Related Links

http://www.stjude.org

St. Jude Children's Research Hospital

Other Identifiers

OPBMT2

Identifier Type: -

Identifier Source: org_study_id