Severe OsteopetrosisPhase 2/3NCT00775931
Allogeneic Transplantation For Severe Osteopetrosis
A Phase 2/3 study testing umbilical cord blood transplantation, Campath-1H and Total Lymphoid Irradiation in people with Severe Osteopetrosis, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial summary
The purpose of this research is to explore what we believe may be 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 more about this study
- Who is it for?
- Ages 1 day to 45 years
- Conditions the study is for
- Severe Osteopetrosis
- What is being tested?
- umbilical cord blood transplantation, Campath-1H 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
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2008to Jun 2013
- Phase
- Phase 2/3
- 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 1 day 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 < or = 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 significantly 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: Allogeneic Hematopoietic Stem Cell Transplantation For Severe Osteopetrosis
The purpose of this research is to explore what we believe may be 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. Prior multi-institutional data in past studies found that approximately 30% of Osteopetrosis patients do not engraft. Therefore, in this study, we utilize a reduced intensity design 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.
Read the detailed description
This revised transplant protocol will test the following: 1) the ability to achieve engraftment with the reduced intensity protocol and a second infusion of stem cells on day 42, 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, and evaluation of blood parameters and genes that may be important in the disease process. In older patients, studies to evaluation osteoclast differentiation and function will also be offered.
- Conditions
- Severe Osteopetrosis
- Being tested
- umbilical cord blood transplantation, Campath-1H, Total Lymphoid Irradiation, Cyclophosphamide, Busulfan
- 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.
umbilical cord blood transplantationProcedure or surgery
Also called UCBT
Umbilical cord blood will be collected, processed and shipped according to existing protocols. 2 cord blood units will be utilized if available. The choice of units will be based on the HLA typing standards of the University of Minnesota Blood and Marrow Program. If 2 units are not available, a single unit may be used. If a single unit is used, the unit should provide at least 10 x 107 nucleated cells/kg recipient body weight.
Campath-1HDrug
Also called Alemtuzumab
Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19.
Total Lymphoid IrradiationRadiation
Also called TLI
Dose 500 cGy via anteroposterior (AP) and posteroanterior(PA) fields (250 cGy AP and 250 cGy PA).
CyclophosphamideDrug
Also called Cytoxan
Cyclophosphamide (50 mg/kg/dose) will be given IV on day -4, -3, -2 and -1 over 2 hours. The total dose to be given over 4 days is 200 mg/kg for cord blood grafts-receiving patients only.
BusulfanDrug
Also called Busulfex
patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients.
Fludarabine monophosphateDrug
Also called Fludara
Fludarabine (35 mg/m2 daily for 5 days, 175 mg/m2 total) will be administered IV over 30 minutes on days -6, -5, -4, -3, and -2 for donor grafts-receiving patients only.
marrow graft transplantationProcedure or surgery
Also called HSCT
Related donor marrow will be collected, processed and shipped according to existing protocols of the National Marrow Donor Program or other URD registry, with the goal of achieving a cell dose of ≥ 6.0 x 108 nucleated cells/kg. The proportion of cells that are CD34+ will be determined prior to the administration of the graft. This will allow a portion of the graft (2 x 106 CD34+ cells) to be frozen for a subsequent infusion on day +42.
| Study group | Role | What they receive |
|---|---|---|
| marrow graft transplant conditioning | Active comparator | Pre-transplant conditioning using Campath-1H, Busulfan, Fludarabine monophosphate, and total lymphoid irradiation followed by unrelated or matched related donor marrow graft transplantation (both peripheral blood and marrow) and a second CD34 cell infusion on Day 42. Receives: Drug: Campath-1H; Radiation: Total Lymphoid Irradiation; Drug: Busulfan; Drug: Fludarabine monophosphate; Procedure: marrow graft transplantation |
| cord blood transplant conditioning | Active comparator | Pre-transplant conditioning using Campath-1H, Busulfan and Cyclophosphamide followed by unrelated umbilical cord blood transplantation and a second smaller portion cord blood graft infusion on Day 42. Receives: Procedure: umbilical cord blood transplantation; Drug: Campath-1H; Drug: Cyclophosphamide; Drug: Busulfan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients Who Achieved Donor Cell Engraftment
Measured: Day 100
Secondary outcomes (3)
Transplant Related Mortality at 100 Days
Measured: day 100
Transplant Related Toxicity
Measured: Day 100 post transplant
Incidence of Grade II - IV Acute Graft-versus-host Disease
Measured: by Day 100 after transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2008 (estimated)
- Study startAug 2008
- Primary completionJun 2013
- Study completionJun 2013
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 Severe OsteopetrosisStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Paul Orchard, MD, Principal investigator, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00775931
- Sponsor's protocol ID
- MT2008-20
- Other IDs
- 0808M42261
- Status last verified
- Jul 2019
- First submitted
- 16 Oct 2008
- Last updated
- 31 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Allogeneic Hematopoietic Stem Cell Transplantation For Severe Osteopetrosis
- ClinicalTrials.gov ID
- NCT00775931
- Acronym / sponsor ID
- MT2008-20
- Conditions
- Severe Osteopetrosis
- Keywords
- osteopetrosis
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- Aug 2008
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 20 Oct 2008 (estimated)
- Results
- Posted 31 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research is to explore what we believe may be 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. Prior multi-institutional data in past studies found that approximately 30% of Osteopetrosis patients do not engraft. Therefore, in this study, we utilize a reduced intensity design 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.
Detailed description
This revised transplant protocol will test the following: 1) the ability to achieve engraftment with the reduced intensity protocol and a second infusion of stem cells on day 42, 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, and evaluation of blood parameters and genes that may be important in the disease process. In older patients, studies to evaluation osteoclast differentiation and function will also be offered.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| marrow graft transplant conditioning | Active comparator | Drug: Campath-1H, Radiation: Total Lymphoid Irradiation, Drug: Busulfan, Drug: Fludarabine monophosphate, Procedure: marrow graft transplantationPre-transplant conditioning using Campath-1H, Busulfan, Fludarabine monophosphate, and total lymphoid irradiation followed by unrelated or matched related donor marrow graft transplantation (both peripheral blood and marrow) and a second CD34 cell infusion on Day 42. |
| cord blood transplant conditioning | Active comparator | Procedure: umbilical cord blood transplantation, Drug: Campath-1H, Drug: Cyclophosphamide, Drug: BusulfanPre-transplant conditioning using Campath-1H, Busulfan and Cyclophosphamide followed by unrelated umbilical cord blood transplantation and a second smaller portion cord blood graft infusion on Day 42. |
Who may qualify
- Ages
- 1 day to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- Patients eligible for transplantation under this protocol will be < or = 45 years of age, and will be diagnosed with severe osteopetrosis. This will be defined as having the following manifestations of the disease.
- 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.
Key exclusion criteria (8 listed)
- Patients >45 years of age
- Evidence of hepatic failure
- Pulmonary dysfunction sufficient to significantly 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 |
|---|---|---|
| umbilical cord blood transplantationAlso: UCBTUmbilical cord blood will be collected, processed and shipped according to existing protocols. 2 cord blood units will be utilized if available. The choice of units will be based on the HLA typing standards of the University of Minnesota Blood and Marrow Program. If 2 units are not available, a single unit may be used. If a single unit is used, the unit should provide at least 10 x 107 nucleated cells/kg recipient body weight. | Procedure or surgery | cord blood transplant conditioning |
| Campath-1HAlso: AlemtuzumabCampath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. | Drug | cord blood transplant conditioning, marrow graft transplant conditioning |
| Total Lymphoid IrradiationAlso: TLIDose 500 cGy via anteroposterior (AP) and posteroanterior(PA) fields (250 cGy AP and 250 cGy PA). | Radiation | marrow graft transplant conditioning |
| CyclophosphamideAlso: CytoxanCyclophosphamide (50 mg/kg/dose) will be given IV on day -4, -3, -2 and -1 over 2 hours. The total dose to be given over 4 days is 200 mg/kg for cord blood grafts-receiving patients only. | Drug | cord blood transplant conditioning |
| BusulfanAlso: Busulfexpatients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients. | Drug | cord blood transplant conditioning, marrow graft transplant conditioning |
| Fludarabine monophosphateAlso: FludaraFludarabine (35 mg/m2 daily for 5 days, 175 mg/m2 total) will be administered IV over 30 minutes on days -6, -5, -4, -3, and -2 for donor grafts-receiving patients only. | Drug | marrow graft transplant conditioning |
| marrow graft transplantationAlso: HSCTRelated donor marrow will be collected, processed and shipped according to existing protocols of the National Marrow Donor Program or other URD registry, with the goal of achieving a cell dose of ≥ 6.0 x 108 nucleated cells/kg. The proportion of cells that are CD34+ will be determined prior to the administration of the graft. This will allow a portion of the graft (2 x 106 CD34+ cells) to be frozen for a subsequent infusion on day +42. | Procedure or surgery | marrow graft transplant conditioning |
Primary outcome
Number of Patients Who Achieved Donor Cell Engraftment
Time frame: Day 100
3 secondary outcomes
Transplant Related Mortality at 100 Days
Time frame: day 100
Transplant Related Toxicity
Time frame: Day 100 post transplant
Incidence of Grade II - IV Acute Graft-versus-host Disease
Time frame: by Day 100 after transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Severe Osteopetrosis
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 2/3 study testing umbilical cord blood transplantation, Campath-1H and Total Lymphoid Irradiation in people with Severe 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 8 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: finished, as of the sponsor's last update on 31 Jul 2019. 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 31 Jul 2019). 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 Who Achieved 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 31 Jul 2019; AzTrials last refreshed its copy on 31 Oct 2026.