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Stem Cell Transplantation for Children Affected With Osteopetrosis

This study has been terminated.
(Due to the principal investigator having left the institution.)
Information provided by (Responsible Party):
St. Jude Children's Research Hospital Identifier:
First received: September 1, 2005
Last updated: July 26, 2012
Last verified: January 2011
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.

Condition Intervention
Procedure: Stem Cell Transplantation
Device: Miltenyi Biotec CliniMACS
Drug: Systemic chemotherapy and antibodies

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Allogeneic Hematopoietic Stem Cell Transplantation for Children Affected With Malignant Osteopetrosis: A Pilot Study

Resource links provided by NLM:

Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • Engraftment [ Time Frame: 100 days post-transplant ]
    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.

Enrollment: 15
Study Start Date: July 2004
Study Completion Date: February 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1 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.
Other Names:
  • Haploidentical stem cell transplant
  • Allogeneic stem cell transplant
Device: Miltenyi Biotec CliniMACS
Stem cell selection device
Other Name: T-cell depletion
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.

Other Name: Transplantation for Osteopetrosis

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

Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
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Please refer to this study by its identifier: NCT00145587

United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Sponsors and Collaborators
St. Jude Children's Research Hospital
Principal Investigator: Kimberly A Kasow, DO St. Jude Children's Research Hospital
  More Information

Additional Information:
Responsible Party: St. Jude Children's Research Hospital Identifier: NCT00145587     History of Changes
Other Study ID Numbers: OPBMT2
Study First Received: September 1, 2005
Results First Received: June 22, 2011
Last Updated: July 26, 2012

Keywords provided by St. Jude Children's Research Hospital:
Autosomal recessive bone disease
Haploidentical stem cell transplantation
Allogeneic stem cell transplantation
T-cell depletion methodology
Miltenyi Biotec CliniMACS stem cell selection device

Additional relevant MeSH terms:
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Immunologic Factors
Physiological Effects of Drugs processed this record on April 26, 2017