Stem Cell Transplantation for Children Affected With Osteopetrosis - Full Text View

Purpose

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

Genetics Home Reference related topics:

Melnick-Needles syndrome

Drug Information available for:

Cyclophosphamide Melphalan Thiotepa Fludarabine Fludarabine monophosphate Rituximab Cyclosporine Cyclosporin Melphalan hydrochloride Sarcolysin Busulfan Muromonab CD3

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

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

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

Primary Outcome Measures:

To determine the feasibility of engraftment by 100 days after transplantation for children with osteopetrosis who receive a haploidentical hematopoietic stem cell graft. [ Time Frame: July 2009 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	28
Study Start Date:	July 2004
Estimated Study Completion Date:	July 2010
Estimated Primary Completion Date:	July 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.

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 PTLPD. In addition to T-cell depletion of the donor product, cyclosporine will be provided as prophylaxis for GVHD.

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.

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

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00145587

Contacts


Contact: Kimberly A Kasow, DO	1-866-278-5833	Kimberly.kasow@stjude.org

Locations


United States, Tennessee
	St. Jude Children's Research Hospital	Recruiting
	Memphis, Tennessee, United States, 38105
	Contact: Kimberly A Kasow, DO 866-278-5833 Kimberly.kasow@stjude.org
	Principal Investigator: Kimberly A Kasow, DO

Sponsors and Collaborators

St. Jude Children's Research Hospital

Investigators


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

More Information

St. Jude Children's Research Hospital This link exits the ClinicalTrials.gov site

Responsible Party:	St. Jude Children's Research Hospital ( Kimberly A Kasow, DO / Principal Investigator )
Study ID Numbers:	OPBMT2
First Received:	September 1, 2005
Last Updated:	May 1, 2008
ClinicalTrials.gov Identifier:	NCT00145587
Health Authority:	United States: Food and Drug Administration

Keywords provided by St. Jude Children's Research Hospital:

Osteopetrosis

Autosomal recessive bone disease

Haploidentical stem cell transplantation

Allogeneic stem cell transplantation

T-cell depletion methodology

Miltenyi Biotec CliniMACS stem cell selection device

Study placed in the following topic categories:

Melphalan

Cyclosporine

Rituximab

Osteochondrodysplasias

Cyclophosphamide

Fludarabine monophosphate

Cyclosporins

Bone Diseases

Albers-Schonberg disease

Muromonab-CD3

Thiotepa

Osteopetrosis

Antibodies

Musculoskeletal Diseases

Busulfan

Bone Diseases, Developmental

Fludarabine

Additional relevant MeSH terms:

Osteosclerosis

ClinicalTrials.gov processed this record on October 31, 2008

Sponsored by:	St. Jude Children's Research Hospital
Information provided by:	St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:	NCT00145587