OsteopetrosisPhase 2NCT00638820
Reduced Intensity AlloTransplant For Osteopetrosis
A Phase 2 study testing Stem Cell or Umbilical Cord Blood Transplantation, Campath, Busulfan, Clofarabine and Total Lymphoid Irradiation in people with Osteopetrosis, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial summary
We believe that hematopoietic stem cell transplantation (HSCT) will help subjects with Osteopetrosis generate functioning osteoclasts, and by so doing assist in the resolution of the abnormal bone architecture, and the anemia and bone marrow failure that is also characteristic of this disease. Read more about this study
- Who is it for?
- Ages Up to 45 years
- Conditions the study is for
- Osteopetrosis
- What is being tested?
- Stem Cell or Umbilical Cord Blood Transplantation, Campath, Busulfan, Clofarabine and Total Lymphoid Irradiation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2007to May 2008
- Phase
- Phase 2
- 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 Up to 45 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients eligible for transplantation under this protocol will be <45 years of age, and will be diagnosed with severe osteopetrosis. This will be defined as having the following manifestations of the disease.
- Bones that are uniformly markedly dense based on skeletal survey
- No history that would suggest autosomal dominant inheritance
- Evidence of hematologic changes that are attributed to the underlying disease, including the need for ongoing transfusions, OR
- the presence of progressive anemia or thrombocytopenia, OR a white blood cell differential with a predominance of immature forms and evidence of extramedullary hematopoiesis, OR
- persistence of serious infectious complications that are thought to be due to the abnormal architecture of the bone that are resistant to surgical and medical interventions.
Who cannot join
- Patients >45 years of age
- Evidence of hepatic failure
- pulmonary dysfunction sufficient to substantially increase the risk of transplant
- Renal dysfunction with glomerular filtration rate (GFR) <30% of predicted.
- Cardiac compromise sufficient to substantially increase the risk of transplantation
- Severe, stable neurologic impairment.
- Human immunodeficiency virus (HIV) positivity.
- Pregnant or lactating females
Trial locations and contacts
1 site in 1 country.
United States1 site
University of MInnesota, Fairview
Minneapolis, Minnesota, 55455
About this study
Official title: Reduced Intensity Allogeneic Transplantation For Severe Osteopetrosis Incorporating A Second Cd34 Selected Graft
We believe that hematopoietic stem cell transplantation (HSCT) will help subjects with Osteopetrosis generate functioning osteoclasts, and by so doing assist in the resolution of the abnormal bone architecture, and the anemia and bone marrow failure that is also characteristic of this disease. However, we have found in past studies that approximately 30% of Osteopetrosis patients do not engraft. Therefore, in this study, we plan to use a different combination of pre-transplant drugs to try to make transplants safer for this disease, as well as to provide a second infusion of stem cells in patients with matched related or unrelated donors. The purpose of this research is to find a safer and more effective means of performing stem cell transplantation in patients with Osteopetrosis, using chemotherapy and radiation designed to bring about engraftment and lessen transplant mortality.
Read the detailed description
This transplant protocol will test the following: 1) the ability to achieve engraftment with the reduced intensity protocol, 2) the mortality associated with transplant by day 100, 3) patient outcomes, based on differential imaging and biologic evaluations prior to transplantation and at designated points after transplantation (day 100, 6 months, 1, 2 and 5 years). Additional biologic studies will include microarray analysis, Campath levels just prior to the administration of the graft, and establishment of mesenchymal stem cell lines. In older patients, studies to evaluation osteoclast differentiation and function will also be offered.
- Conditions
- Osteopetrosis
- Being tested
- Stem Cell or Umbilical Cord Blood Transplantation, Campath, Busulfan, Clofarabine, Total Lymphoid Irradiation
- Keywords
- osteopetrosis
- 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 or Umbilical Cord Blood TransplantationProcedure or surgery
Also called Bone Marrow Transplant
Stem Cell (unrelated or matched related donor grafts (both peripheral blood and marrow) infusion on Day 0 and 42; Umbilical Cord Blood on Day 0 and 42
Campath, Busulfan, ClofarabineDrug
Also called Busulfex, Clolar,Alemtuzumab
- 12 Campath-1H 0.3 mg/kg intravenously (IV) over 2 hours
- 11 Campath-1H 0.3 mg/kg intravenously over 2 hours
- 10 Campath-1H 0.3 mg/kg intravenously over 2 hours
- 9 Busulfan <12 kg: 2.2 mg/kg/dose IV every 12 hours >12 kg: 1.6 mg/kg/dose IV every 12 hours
- 8 Busulfan <12 kg: 2.2 mg/kg/dose IV every 12 hours >12 kg: 1.6 mg/kg/dose IV every 12 hours
- 7 "Rest"
- 6 Clofarabine 40 mg/m2 intravenously over 2 hours
- 5 Clofarabine 40 mg/m2 intravenously over 2 hours
- 4 Clofarabine 40 mg/m2 intravenously over 2 hours
- 3 Clofarabine 40 mg/m2 intravenously over 2 hours
- 2 Clofarabine 40 mg/m2 intravenously over 2 hours
Total Lymphoid IrradiationProcedure or surgery
Also called Therapuetic radation, radiation therapy
Dose 500 cGy via anteroposterior (AP) and posteroanterior (PA) fields (250 cGy AP and 250 cGy PA).
| Study group | Role | What they receive |
|---|---|---|
| Intent-To-Treat | Experimental | Patients enrolled and received study treatment. Receives: Procedure: Stem Cell or Umbilical Cord Blood Transplantation; Drug: Campath, Busulfan, Clofarabine; Procedure: Total Lymphoid Irradiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients Achieving Donor Cell Engraftment
Number of patients with persistent presence of donor-derived cells at Day 100
Measured: Day 100
Secondary outcomes (3)
Number of Patients With Transplant Related Death
Number of participants died during study by Day 100 and reason for death was related to transplant.
Measured: Day 100
Number of Patients With Transplant Related Toxicity
Number of patients experiencing adverse effects due to transplant categorized by body system using Common Terminology Criteria for Adverse Events coding from the National Cancer Institute, Version 3.0.
Measured: Day 100
Differential Imaging and Biologic Evaluations
These outcome measures were not assessed due to early study termination.
Measured: Day 100, 6 months, 1, 2 and 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2008 (estimated)
- Study startSep 2007
- Primary completionMay 2008
- Study completionMay 2008
Why it stopped: Excess toxicity
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 Masonic Cancer Center, University of MinnesotaThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Investigators
- Paul Orchard, MD, Principal investigator, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00638820
- Sponsor's protocol ID
- 0704M06581
- Other IDs
- MT2007-06
- Status last verified
- Dec 2017
- First submitted
- 11 Mar 2008
- Last updated
- 28 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reduced Intensity Allogeneic Transplantation For Severe Osteopetrosis Incorporating A Second Cd34 Selected Graft
- ClinicalTrials.gov ID
- NCT00638820
- Acronym / sponsor ID
- 0704M06581
- Conditions
- Osteopetrosis
- Keywords
- osteopetrosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Excess toxicity
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- Sep 2007
- Primary completion
- May 2008 (actual)
- Study completion
- May 2008 (actual)
- First posted
- 19 Mar 2008 (estimated)
- Results
- Posted 3 Feb 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
We believe that hematopoietic stem cell transplantation (HSCT) will help subjects with Osteopetrosis generate functioning osteoclasts, and by so doing assist in the resolution of the abnormal bone architecture, and the anemia and bone marrow failure that is also characteristic of this disease. However, we have found in past studies that approximately 30% of Osteopetrosis patients do not engraft. Therefore, in this study, we plan to use a different combination of pre-transplant drugs to try to make transplants safer for this disease, as well as to provide a second infusion of stem cells in patients with matched related or unrelated donors. The purpose of this research is to find a safer and more effective means of performing stem cell transplantation in patients with Osteopetrosis, using chemotherapy and radiation designed to bring about engraftment and lessen transplant mortality.
Detailed description
This transplant protocol will test the following: 1) the ability to achieve engraftment with the reduced intensity protocol, 2) the mortality associated with transplant by day 100, 3) patient outcomes, based on differential imaging and biologic evaluations prior to transplantation and at designated points after transplantation (day 100, 6 months, 1, 2 and 5 years). Additional biologic studies will include microarray analysis, Campath levels just prior to the administration of the graft, and establishment of mesenchymal stem cell lines. In older patients, studies to evaluation osteoclast differentiation and function will also be offered.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intent-To-Treat | Experimental | Procedure: Stem Cell or Umbilical Cord Blood Transplantation, Drug: Campath, Busulfan, Clofarabine, Procedure: Total Lymphoid IrradiationPatients enrolled and received study treatment. |
Who may qualify
- Ages
- Up to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Patients eligible for transplantation under this protocol will be <45 years of age, and will be diagnosed with severe osteopetrosis. This will be defined as having the following manifestations of the disease.
- Bones that are uniformly markedly dense based on skeletal survey
- No history that would suggest autosomal dominant inheritance
- Evidence of hematologic changes that are attributed to the underlying disease, including the need for ongoing transfusions, OR
- the presence of progressive anemia or thrombocytopenia, OR a white blood cell differential with a predominance of immature forms and evidence of extramedullary hematopoiesis, OR
Key exclusion criteria (8 listed)
- Patients >45 years of age
- Evidence of hepatic failure
- pulmonary dysfunction sufficient to substantially increase the risk of transplant
- Renal dysfunction with glomerular filtration rate (GFR) <30% of predicted.
- Cardiac compromise sufficient to substantially increase the risk of transplantation
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 or Umbilical Cord Blood TransplantationAlso: Bone Marrow TransplantStem Cell (unrelated or matched related donor grafts (both peripheral blood and marrow) infusion on Day 0 and 42; Umbilical Cord Blood on Day 0 and 42 | Procedure or surgery | Intent-To-Treat |
| Campath, Busulfan, ClofarabineAlso: Busulfex, Clolar,Alemtuzumab* 12 Campath-1H 0.3 mg/kg intravenously (IV) over 2 hours * 11 Campath-1H 0.3 mg/kg intravenously over 2 hours * 10 Campath-1H 0.3 mg/kg intravenously over 2 hours * 9 Busulfan <12 kg: 2.2 mg/kg/dose IV every 12 hours >12 kg: 1.6 mg/kg/dose IV every 12 hours * 8 Busulfan <12 kg: 2.2 mg/kg/dose IV every 12 hours >12 kg: 1.6 mg/kg/dose IV every 12 hours * 7 "Rest" * 6 Clofarabine 40 mg/m2 intravenously over 2 hours * 5 Clofarabine 40 mg/m2 intravenously over 2 hours * 4 Clofarabine 40 mg/m2 intravenously over 2 hours * 3 Clofarabine 40 mg/m2 intravenously over 2 hours * 2 Clofarabine 40 mg/m2 intravenously over 2 hours | Drug | Intent-To-Treat |
| Total Lymphoid IrradiationAlso: Therapuetic radation, radiation therapyDose 500 cGy via anteroposterior (AP) and posteroanterior (PA) fields (250 cGy AP and 250 cGy PA). | Procedure or surgery | Intent-To-Treat |
Primary outcome
Number of Patients Achieving Donor Cell Engraftment
Time frame: Day 100
Number of patients with persistent presence of donor-derived cells at Day 100
3 secondary outcomes
Number of Patients With Transplant Related Death
Time frame: Day 100
Number of Patients With Transplant Related Toxicity
Time frame: Day 100
Differential Imaging and Biologic Evaluations
Time frame: Day 100, 6 months, 1, 2 and 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Osteopetrosis
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
Primary Immunodeficiency (PID), Congenital Bone Marrow Failure Syndromes
Active, not recruitingPhase 2
MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
Mucopolysaccharidosis Disorders, Hurler Syndrome
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.
Paul Orchard, MD principal investigator
Masonic Cancer Center, University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Stem Cell or Umbilical Cord Blood Transplantation, Campath, Busulfan, Clofarabine and Total Lymphoid Irradiation in people with Osteopetrosis, run by Masonic Cancer Center, University of Minnesota 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 6 inclusion and 8 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 28 Dec 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Feb 2010). 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?
Number of Patients Achieving Donor Cell Engraftment (time frame: Day 100). 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 28 Dec 2017.