Stem Cell Transplantation for Children Affected With Osteopetrosis

April 24, 2017 updated by: St. Jude Children's Research Hospital

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • St. Jude Children's Research Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: 1
Device: Miltenyi Biotec CliniMACS
Stem cell selection device
Other Names:
  • T-cell depletion
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:
  • Allogeneic stem cell transplant
  • Haploidentical stem cell transplant
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 Names:
  • Transplantation for Osteopetrosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
100 days post-transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

St. Jude Children's Research Hospital

Investigators

  • Principal Investigator: Kimberly A Kasow, DO, St. Jude Children's Research Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2004

Primary Completion (Actual)

February 1, 2009

Study Completion (Actual)

February 1, 2009

Study Registration Dates

First Submitted

September 1, 2005

First Submitted That Met QC Criteria

September 2, 2005

First Posted (Estimate)

September 5, 2005

Study Record Updates

Last Update Posted (Actual)

May 30, 2017

Last Update Submitted That Met QC Criteria

April 24, 2017

Last Verified

January 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OPBMT2

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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