Stem Cell Transplantation for Children Affected With Osteopetrosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00145587
Recruitment Status : Terminated (Due to the principal investigator having left the institution.)
First Posted : September 5, 2005
Results First Posted : August 22, 2011
Last Update Posted : May 30, 2017
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

September 1, 2005
September 5, 2005
June 22, 2011
August 22, 2011
May 30, 2017
July 2004
February 2009   (Final data collection date for primary outcome measure)
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.
To determine the feasibility of engraftment by 100 days after transplantation for children with osteopetrosis who receive a haploidentical hematopoietic stem cell graft.
Complete list of historical versions of study NCT00145587 on Archive Site
Not Provided
  • To study the outcome (good and bad) of stem cell transplantation in children with malignant osteopetrosis one year after transplant who receive either a matched sibling donor transplant or a haploidentical stem cell transplant.
  • To study the genetics of patients, parents and siblings of children with malignant osteopetrosis
Not Provided
Not Provided
Stem Cell Transplantation for Children Affected With Osteopetrosis
Allogeneic Hematopoietic Stem Cell Transplantation for Children Affected With Malignant Osteopetrosis: A Pilot Study
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.

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
Not Applicable
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • 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
  • Procedure: Stem Cell Transplantation
  • Device: Miltenyi Biotec CliniMACS
  • Drug: Systemic chemotherapy and antibodies
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
February 2009
February 2009   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
Child, Adult, Senior
Contact information is only displayed when the study is recruiting subjects
United States
Not Provided
Not Provided
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital
Not Provided
Principal Investigator: Kimberly A Kasow, DO St. Jude Children's Research Hospital
St. Jude Children's Research Hospital
January 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP