Sickle Cell DiseasePhase 2NCT00957931
Allo-HCT MUD for Non-malignant Red Blood Cell (RBC) Disorders: Sickle Cell, Thal, and DBA: Reduced Intensity Conditioning, Co-tx MSCs
A Phase 2 study testing Bone marrow transplantation and Mesenchymal Stromal Cells in people with Sickle Cell Disease and Thalassemia, run by Stanford University at 2 sites in United States.
Trial summary
The main purpose of this project is to cure patients with high risk Sickle cell disease and other red cell disorders including thalassemia and diamond-blackfan anemia by bone marrow transplantation. Read more about this study
- Who is it for?
- Ages 1 year to 25 years
- Conditions the study is for
- Sickle Cell Disease, Thalassemia, Diamond-Blackfan Anemia
- What is being tested?
- Bone marrow transplantation and Mesenchymal Stromal Cells
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 2 sitesUnited States
- Study dates
- Mar 2009to Aug 2013
- 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 1 year to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients with sickle cell disease (SCD) 1-25 years of age with an HLA-identical, but unrelated, donor or 1 human leukocyte antigen (HLA) allele mismatched bone marrow or up to 2 HLA antigen mismatched umbilical cord blood (UCB) donor with one or more of the following:
- Stroke, central nervous system (CNS) hemorrhage or a neurologic event lasting longer than 24 hours.
- Acute chest syndrome with a history of recurrent hospitalizations or exchange transfusions.
- Recurrent vaso-occlusive pain, 3 or more episodes per year for 3 years or more years; or recurrent priapism.
- Impaired neuropsychological function and/or abnormal cerebral MRI scan or abnormal transcranial Doppler (TCD).
- Stage I or II sickle lung disease.
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- Sickle nephropathy (moderate or severe proteinuria or a glomerular filtration rate (GFR) 30-50% of the predicted normal value).
- Bilateral proliferative retinopathy and major visual impairment in at least one eye.
- Osteonecrosis of multiple joints with documented destructive changes.
- Requirement for chronic transfusions but with RBC alloimmunization >2 antibodies during long term transfusion therapy.
- Failure of hydroxyurea (HU) therapy.
- Patients aged 0-21 years with transfusion dependent alpha- or beta-thalassemia who have an HLA-identical or 1 HLA allele mismatched bone marrow or up to 2 HLA mismatched UCB donor.
- Patients aged 0-21 years with Diamond-Blackfan anemia who have an HLA-identical or 1 HLA allele mismatched bone marrow or up to 2 HLA mismatched UCB donor. Diamond- Blackfan anemia patients will only be eligible if they have failed steroid therapy.
Who cannot join
- Patients with one or more of the following:
- Karnofsky or Lansky performance score <70 (See Appendices I and II).
- Stage III-IV lung disease (Appendix III).
- GFR<30% predicted normal values.
- Pregnant or lactating females.
- Active serious infection whereby patient has been on intravenous antibiotics for one week prior to study entry.
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- Any patient with AIDS or HIV seropositivity.
- Any patient with invasive aspergillus infection within one year of study entry.
- Psychologically incapable of undergoing bone marrow transplant (BMT) with associated strict isolation or documented history of medical non-compliance.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Children's Hospital of Alabama
Birmingham, Alabama, 35233
University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: Pilot Study MUD HCT:Pts High Risk Sickle Cell,Other Non-Malignant RBC Disorders- Reduced Intensity Preparative Regimen, HAPLO-Identical Mesenchymal Stromal Cells
The main purpose of this project is to cure patients with high risk Sickle cell disease and other red cell disorders including thalassemia and diamond-blackfan anemia by bone marrow transplantation. The patients enrolled in this study will be those who lack matched sibling donors and therefore have no other option but to undergo bone marrow transplantation using matched but unrelated bone marrow or umbilical cord blood from the national marrow donor program registry. Since bone marrow transplantation for these disorders using matched unrelated donors has two major problems i.e. engraftment, or , the process of new marrow being accepted and allowed to grow in the the patient; and graft-versus-host disease, or the process where the new marrow "rejects" the host or the patient, this study has been devised with methods to overcome these two problems and thus make transplantation from unrelated donors both successful in terms of engraftment and safe in terms of side effects, both acute and long term.
In order to accomplish these two goals, two important things will be done. Firstly, patients will get three medicines which are considered reduced intensity because they are not known to cause the serious organ damage seen with conventional chemotherapy. These medicines, however, do cause intense immune suppression so these can cause increased infections. Secondly, in addition to transplantation of bone marrow from unrelated donors, patients will also transplanted with mesenchymal stromal cells derived from the bone marrow of their parents. Mesenchymal stromal cells are adult stem cells that are normally found in the bone marrow and are thought to create the right background for the blood cells to grow. They have been shown in many animal and human studies to improve engraftment. In addition, they have a special property by which they prevent and are now even considered to treat graft versus host disease. Therefore, by using a reduced intensity chemotherapy regimen before transplant and transplanting mesenchymal stromal cells, we hope to improve engraftment while at the same time decrease the potential for severe side effects associated with a conventional transplant which uses extremely high doses of chemotherapy.
- Conditions
- Sickle Cell Disease, Thalassemia, Diamond-Blackfan Anemia
- Being tested
- Bone marrow transplantation, Mesenchymal Stromal Cells
- Medical subject headings
- Anemia, Sickle Cell, Thalassemia, Anemia, Diamond-Blackfan
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bone marrow transplantationProcedure or surgery
Bone marrow transplantation using matched unrelated donors, reduced intensity conditioning regimen, and co-transplanting mesenchymal stromal cells derived from parental bone marrow.
Mesenchymal Stromal CellsBiological
| Study group | Role | What they receive |
|---|---|---|
| Mesenchymal stromal cells | Experimental | Not described Receives: Procedure: Bone marrow transplantation; Biological: Mesenchymal Stromal Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Count of Participants With Stable Engraftment Post Hematopoietic Cell Transplantation (HCT)
Stable engraftment was defined as absolute neutrophil count (ANC) >500 cells /µL for 3 consecutive days and platelet count >50,000 for one week without transfusion; subsequently stable engraftment was measured by percentage of donor cells.
Measured: Up to 1 year
Secondary outcomes (4)
Overall Survival 6 Months Following HCT
Overall survival is reported at the count of participants alive 6 months following HCT.
Measured: 6 months
Overall Survival 1 Year Following HCT
Overall survival is reported at the count of participants alive 1 year following HCT.
Measured: 1 year
Count of Participants With Disease-free Survival 6 Months Following HCT
Disease-free survival is defined as alive without underlying disease.
Measured: 6 months
Count of Participants With Disease-free Survival 1 Year Following HCT
Disease-free survival is defined as alive without underlying disease.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2009 (estimated)
- Study startMar 2009
- Primary completionAug 2013
- Study completionAug 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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe 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
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Minnesota, University of Alabama at Birmingham
- Responsible party
- Principal investigator, Sandhya Kharbanda, Stanford University
- Investigators
- Sandhya Kharbanda, M.D., Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00957931
- Sponsor's protocol ID
- MSC01
- Status last verified
- Jul 2018
- First submitted
- 12 Aug 2009
- Last updated
- 6 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Kharbanda S, Smith AR, Hutchinson SK, McKenna DH, Ball JB, Lamb LS Jr, Agarwal R, Weinberg KI, Wagner JE Jr. Unrelated donor allogeneic hematopoietic stem cell transplantation for patients with hemoglobinopathies using a reduced-intensity conditioning regimen and third-party mesenchymal stromal cells. Biol Blood Marrow Transplant. 2014 Apr;20(4):581-6. doi: 10.1016/j.bbmt.2013.12.564. Epub 2013 Dec 24.
PubMed 24370862
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study MUD HCT:Pts High Risk Sickle Cell,Other Non-Malignant RBC Disorders- Reduced Intensity Preparative Regimen, HAPLO-Identical Mesenchymal Stromal Cells
- ClinicalTrials.gov ID
- NCT00957931
- Acronym / sponsor ID
- MSC01
- Conditions
- Sickle Cell Disease, Thalassemia, Diamond-Blackfan Anemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- University of Minnesota, University of Alabama at Birmingham
- Study start
- Mar 2009 (actual)
- Primary completion
- Aug 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 13 Aug 2009 (estimated)
- Results
- Posted 6 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main purpose of this project is to cure patients with high risk Sickle cell disease and other red cell disorders including thalassemia and diamond-blackfan anemia by bone marrow transplantation. The patients enrolled in this study will be those who lack matched sibling donors and therefore have no other option but to undergo bone marrow transplantation using matched but unrelated bone marrow or umbilical cord blood from the national marrow donor program registry. Since bone marrow transplantation for these disorders using matched unrelated donors has two major problems i.e. engraftment, or , the process of new marrow being accepted and allowed to grow in the the patient; and graft-versus-host disease, or the process where the new marrow "rejects" the host or the patient, this study has been devised with methods to overcome these two problems and thus make transplantation from unrelated donors both successful in terms of engraftment and safe in terms of side effects, both acute and long term.
In order to accomplish these two goals, two important things will be done. Firstly, patients will get three medicines which are considered reduced intensity because they are not known to cause the serious organ damage seen with conventional chemotherapy. These medicines, however, do cause intense immune suppression so these can cause increased infections. Secondly, in addition to transplantation of bone marrow from unrelated donors, patients will also transplanted with mesenchymal stromal cells derived from the bone marrow of their parents. Mesenchymal stromal cells are adult stem cells that are normally found in the bone marrow and are thought to create the right background for the blood cells to grow. They have been shown in many animal and human studies to improve engraftment. In addition, they have a special property by which they prevent and are now even considered to treat graft versus host disease. Therefore, by using a reduced intensity chemotherapy regimen before transplant and transplanting mesenchymal stromal cells, we hope to improve engraftment while at the same time decrease the potential for severe side effects associated with a conventional transplant which uses extremely high doses of chemotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Mesenchymal stromal cells | Experimental | Procedure: Bone marrow transplantation, Biological: Mesenchymal Stromal Cells |
Who may qualify
- Ages
- 1 year to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (13 listed)
- Patients with sickle cell disease (SCD) 1-25 years of age with an HLA-identical, but unrelated, donor or 1 human leukocyte antigen (HLA) allele mismatched bone marrow or up to 2 HLA antigen mismatched umbilical cord blood (UCB) donor with one or more of the following:
- Patients aged 0-21 years with transfusion dependent alpha- or beta-thalassemia who have an HLA-identical or 1 HLA allele mismatched bone marrow or up to 2 HLA mismatched UCB donor.
- Patients aged 0-21 years with Diamond-Blackfan anemia who have an HLA-identical or 1 HLA allele mismatched bone marrow or up to 2 HLA mismatched UCB donor. Diamond- Blackfan anemia patients will only be eligible if they have failed steroid therapy.
Key exclusion criteria (9 listed)
- Patients with one or more of the following:
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 |
|---|---|---|
| Bone marrow transplantationBone marrow transplantation using matched unrelated donors, reduced intensity conditioning regimen, and co-transplanting mesenchymal stromal cells derived from parental bone marrow. | Procedure or surgery | Mesenchymal stromal cells |
| Mesenchymal Stromal Cells | Biological | Mesenchymal stromal cells |
Primary outcome
Count of Participants With Stable Engraftment Post Hematopoietic Cell Transplantation (HCT)
Time frame: Up to 1 year
Stable engraftment was defined as absolute neutrophil count (ANC) >500 cells /µL for 3 consecutive days and platelet count >50,000 for one week without transfusion; subsequently stable engraftment was measured by percentage of donor cells.
4 secondary outcomes
Overall Survival 6 Months Following HCT
Time frame: 6 months
Overall Survival 1 Year Following HCT
Time frame: 1 year
Count of Participants With Disease-free Survival 6 Months Following HCT
Time frame: 6 months
Count of Participants With Disease-free Survival 1 Year Following HCT
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24370862Kharbanda S, Smith AR, Hutchinson SK, McKenna DH, Ball JB, Lamb LS Jr, Agarwal R, Weinberg KI, Wagner JE Jr. Unrelated donor allogeneic hematopoietic stem cell transplantation for patients with hemoglobinopathies using a reduced-intensity conditioning regimen and third-party mesenchymal stromal cells. Biol Blood Marrow Transplant. 2014 Apr;20(4):581-6. doi: 10.1016/j.bbmt.2013.12.564. Epub 2013 Dec 24.
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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.
Sandhya Kharbanda, M.D. principal investigator
Stanford University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bone marrow transplantation and Mesenchymal Stromal Cells in people with Sickle Cell Disease and Thalassemia, run by Stanford University at 2 sites 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 13 inclusion and 9 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 6 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 6 Aug 2018). 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?
Count of Participants With Stable Engraftment Post Hematopoietic Cell Transplantation (HCT) (time frame: Up to 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00957931, which also lists 1 linked publication.
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 6 Aug 2018.