OsteopetrosisNCT00145587
Stem Cell Transplantation for Children Affected With Osteopetrosis
A study testing Stem Cell Transplantation, Miltenyi Biotec CliniMACS and Systemic chemotherapy and antibodies in people with Osteopetrosis, run by St. Jude Children's Research Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Osteopetrosis
- What is being tested?
- Stem Cell Transplantation, Miltenyi Biotec CliniMACS and Systemic chemotherapy and antibodies
- Type of treatment
- Injection or infusion, Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2004to Feb 2009
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Clinical diagnosis of malignant osteopetrosis as documented by bone marrow biopsy and radiographic imaging
- A suitable hematopoietic stem cell donor is available
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
About this study
Official title: 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.
Read the 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
- Being tested
- Stem Cell Transplantation, Miltenyi Biotec CliniMACS, Systemic chemotherapy and antibodies
- Keywords
- Osteopetrosis, Autosomal recessive bone disease, Haploidentical stem cell transplantation, Allogeneic stem cell transplantation, T-cell depletion methodology, Miltenyi Biotec CliniMACS stem cell selection device
- Medical subject headings
- Osteopetrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stem Cell TransplantationProcedure or surgery
Also called Haploidentical stem cell transplant, Allogeneic stem cell transplant
An infusion of HLA partially matched family member donor stem cells processed through the use of the investigational Miltenyi Biotec CliniMACS device.
Miltenyi Biotec CliniMACSDevice
Also called T-cell depletion
Stem cell selection device
Systemic chemotherapy and antibodiesDrug
Also called Transplantation for Osteopetrosis
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.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Other | Not described Receives: Procedure: Stem Cell Transplantation; Device: Miltenyi Biotec CliniMACS; Drug: Systemic chemotherapy and antibodies |
What is being measured
The primary outcome is the main question the study is designed to answer.
Engraftment
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.
Measured: 100 days post-transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2005 (estimated)
- Study startJul 2004
- Primary completionFeb 2009
- Study completionFeb 2009
Why it stopped: Due to the principal investigator having left the institution.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for OsteopetrosisStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kimberly A Kasow, DO, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00145587
- Sponsor's protocol ID
- OPBMT2
- Status last verified
- Jan 2011
- First submitted
- 1 Sep 2005
- Last updated
- 30 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Allogeneic Hematopoietic Stem Cell Transplantation for Children Affected With Malignant Osteopetrosis: A Pilot Study
- ClinicalTrials.gov ID
- NCT00145587
- Acronym / sponsor ID
- OPBMT2
- Conditions
- Osteopetrosis
- Keywords
- 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 type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to the principal investigator having left the institution.
- Enrolment
- 15 participants (actual)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Study start
- Jul 2004
- Primary completion
- Feb 2009 (actual)
- Study completion
- Feb 2009 (actual)
- First posted
- 5 Sep 2005 (estimated)
- Results
- Posted 22 Aug 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Other | Procedure: Stem Cell Transplantation, Device: Miltenyi Biotec CliniMACS, Drug: Systemic chemotherapy and antibodies |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Clinical diagnosis of malignant osteopetrosis as documented by bone marrow biopsy and radiographic imaging
- A suitable hematopoietic stem cell donor is available
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Stem Cell TransplantationAlso: Haploidentical stem cell transplant, Allogeneic stem cell transplantAn infusion of HLA partially matched family member donor stem cells processed through the use of the investigational Miltenyi Biotec CliniMACS device. | Procedure or surgery | 1 |
| Miltenyi Biotec CliniMACSAlso: T-cell depletionStem cell selection device | Device | 1 |
| Systemic chemotherapy and antibodiesAlso: Transplantation for OsteopetrosisHaploidentical 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. | Drug | 1 |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- St. Jude Children's Research HospitalLink provided by the sponsor.
Related trials for Osteopetrosis
Active, not recruitingPhase 2
MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
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RecruitingPhase 1/2
Gene-Modified Stem Cell Therapy for Children With Autosomal Recessive Osteopetrosis (ARO)
Osteopetrosis
RecruitingObservational study
Longitudinal Study of Neurodegenerative Disorders
MLD, Krabbe Disease
RecruitingObservational study
Data Collection Study of Patients With Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT With RIC
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RecruitingPhase 2
Reduced Intensity Conditioning for Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT
Primary Immunodeficiency (PID), Congenital Bone Marrow Failure Syndromes
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kimberly A Kasow, DO principal investigator
St. Jude Children's Research Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Stem Cell Transplantation, Miltenyi Biotec CliniMACS and Systemic chemotherapy and antibodies in people with Osteopetrosis, run by St. Jude Children's Research Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 30 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Aug 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Engraftment (time frame: 100 days post-transplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2017.