Sickle Cell DiseasePhase 1NCT00152113
Haploidentical Stem Cell Transplant for Patients With Sickle Cell Disease and Prior Stroke or Abnormal Transcranial Ultrasound
A Phase 1 study testing Hematopoietic Stem Cell Transplantation, CliniMACS and See intervention description in people with Sickle Cell Disease, run by St. Jude Children's Research Hospital at 1 site in United States.
Trial summary
Sickle cell disease is a life-long blood condition that can cause damage to the brain and other organs of the body. Children may develop severe, debilitating clinical states, with stroke or abnormal blood flow to the brain. Read more about this study
- Who is it for?
- Ages 2 to 16 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Hematopoietic Stem Cell Transplantation, CliniMACS and See intervention description
- 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
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2005to Jan 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 2 to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Hemoglobin SS or S-Beta Thalassemia Sickle Cell Disease.
- Partially-matched family member with hemoglobin AA (normal) or hemoglobin AS (sickle trait) phenotype.
- Stroke (persistent neurologic deficit lasting > 24 hours and present on MRI) or abnormal transcranial Doppler (TCD) ultrasonography requiring chronic transfusion therapy. A TCD is deemed abnormal when the velocity is greater than or equal to 200 cm/sec. Chronic transfusion therapy is defined as "packed red blood cell transfusions administered approximately every 3-5 weeks to decrease the percentage of sickle hemoglobin (Hemoglobin S) to prevent complications of sickle cell disease. This is used most commonly to treat/prevent stroke, acute chest syndrome, and/or pain crises.
Who cannot join
- Karnofsky or Lansky score < 60%
- Acute hepatitis or evidence of moderate or severe portal fibrosis on biopsy. (Biopsy will be obtained if patient on chronic transfusion therapy > 6 months or ferritin > 1000 ng/ml) International normalized ratio (INR) less than 2 times normal. ALT and AST less than 3 times the upper limit of normal.
- Severe renal impairment (as evidenced by GFR < 30% predicted normal)
- Ejection fraction or shortening fraction below lower limit of normal for age.
- Pregnancy
- Lactating and pregnant females are excluded
- Positive HLA crossmatch with donor.
- No sickle cell chronic lung disease > Stage 2
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: Hematopoietic Stem Cell Transplantation for Patients With Sickle Cell Disease and Prior Stroke or Abnormal Transcranial Doppler Ultrasound Using Reduced-Intensity Conditioning and T-Cell Depleted HSC From Partially Matched Family Donors
Sickle cell disease is a life-long blood condition that can cause damage to the brain and other organs of the body. Children may develop severe, debilitating clinical states, with stroke or abnormal blood flow to the brain. Treatment generally includes chronic blood transfusions which may cause iron overload, potentially leading to severe and sometimes fatal complications.
Hematopoietic stem cell transplant using cells obtained from a sibling or an unrelated volunteer donor who is a perfect HLA "match" (same tissue type) for the recipient has shown to help, and possibly cure, sickle cell disease. Unfortunately, only about 10-20% of sickle cell patients have a HLA matched sibling donor, and the likelihood of locating an appropriate HLA matched unrelated donor through the various donor registries is limited.
Read more
Stem cells from partially HLA matched family members (also called haploidentical transplant) is an option currently being explored for this patient population. This type of transplant has been used and found to be successful in some patients, mostly those with cancers of the blood. However, there can be significant complications with haploidentical transplant, primarily infection, failure of the graft to grow (graft failure), and a disorder called graft-versus-host disease. In addition, few patients with sickle cell disease have undergone this procedure. Therefore, the risks and benefits of haploidentical transplants for patients with sickle cell disorder are not as well established as those using an HLA identical sibling or unrelated donor.
The primary objective of this study is to assess the safety of haploidentical stem cell transplantation for children and adolescents with severe sickle cell disease and stroke or abnormal transcranial Doppler ultrasound requiring chronic transfusion therapy. The treatment plan will be considered safe if there is not excessive toxicity. Toxicity for this protocol is defined as graft failure/graft rejection, severe acute GVHD, or regimen related death within 100 days after the last cellular product administered.
Of note, the protocol was closed to accrual in September 2007 as we had met the stopping rules related to graft integrity (graft failure and graft rejection). Participants currently enrolled continue to be followed per protocol.
Read the detailed description
Secondary objectives for this protocol include the following:
- To estimate 1-year overall and event free survival after transplantation. An event is defined as toxicity (graft failure, death, grade III/IV acute GHVD), or a sickle-related event (stroke, acute chest syndrome, pain crisis).
- To obtain preliminary information regarding donor engraftment among different cell subsets, including unsorted mononuclear cell, and lymphoid fractions during the first year after transplant.
- To observe the rate of acute and chronic GVHD during the first year after transplant.
- To assess the proportion of research participants who experience poor graft integrity and therefore require additional donor stem cells or lymphocytes.
- To document the effect of stem cell transplant on the central nervous system as defined by radiological imaging and neuropsychological testing.
- To investigate immune reconstitution after transplantation
- Conditions
- Sickle Cell Disease
- Being tested
- Hematopoietic Stem Cell Transplantation, CliniMACS, See intervention description
- Keywords
- Sickle Cell Anemia, Stem Cell Transplantation, Haploidentical stem cell transplant, T cell depletion, CliniMACS device
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hematopoietic Stem Cell TransplantationProcedure or surgery
Allogeneic stem cell transplant Haploidentical stem cell transplant Mismatched family member donor stem cell transplant T cell selection CD34 enrichment
CliniMACSDevice
See intervention descriptionDrug
Hydroxyurea and azathioprine were administered for a 3 month period prior to the initiation of the transplant procedure in an effort to help prevent rejection of the donor product. Approximately 10 days prior to the transplant procedure, all participants received the same preparative regimen consisting of Busulfan, cyclophosphamide, low-dose thiotepa, and OKT3. MMF was administered for GVHD prophylaxis. Two separate infusions of donor stem cells were administered with fixed doses of CD3 and CD34 cells. These haploidentical stem cells were processed using the investigational CliniMACS device.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Other | Not described Receives: Procedure: Hematopoietic Stem Cell Transplantation; Device: CliniMACS; Drug: See intervention description |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the safety of haploidentical stem cell transplantation for children and adolescents with severe sickle cell disease and stroke or abnormal transcranial Doppler ultrasound requiring chronic transfusion therapy.
Measured: September 2007
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2005 (estimated)
- Study startApr 2005
- Primary completionDec 2008
- Study completionJan 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Wing Leung, M.D., Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00152113
- Sponsor's protocol ID
- SCDHAP
- Status last verified
- Feb 2009
- First submitted
- 7 Sep 2005
- Last updated
- 26 Apr 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Dallas MH, Triplett B, Shook DR, Hartford C, Srinivasan A, Laver J, Ware R, Leung W. Long-term outcome and evaluation of organ function in pediatric patients undergoing haploidentical and matched related hematopoietic cell transplantation for sickle cell disease. Biol Blood Marrow Transplant. 2013 May;19(5):820-30. doi: 10.1016/j.bbmt.2013.02.010. Epub 2013 Feb 14.
PubMed 23416852
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hematopoietic Stem Cell Transplantation for Patients With Sickle Cell Disease and Prior Stroke or Abnormal Transcranial Doppler Ultrasound Using Reduced-Intensity Conditioning and T-Cell Depleted HSC From Partially Matched Family Donors
- ClinicalTrials.gov ID
- NCT00152113
- Acronym / sponsor ID
- SCDHAP
- Conditions
- Sickle Cell Disease
- Keywords
- Sickle Cell Anemia, Stem Cell Transplantation, Haploidentical stem cell transplant, T cell depletion, CliniMACS device
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Study start
- Apr 2005
- Primary completion
- Dec 2008 (actual)
- Study completion
- Jan 2009 (actual)
- First posted
- 9 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Sickle cell disease is a life-long blood condition that can cause damage to the brain and other organs of the body. Children may develop severe, debilitating clinical states, with stroke or abnormal blood flow to the brain. Treatment generally includes chronic blood transfusions which may cause iron overload, potentially leading to severe and sometimes fatal complications.
Hematopoietic stem cell transplant using cells obtained from a sibling or an unrelated volunteer donor who is a perfect HLA "match" (same tissue type) for the recipient has shown to help, and possibly cure, sickle cell disease. Unfortunately, only about 10-20% of sickle cell patients have a HLA matched sibling donor, and the likelihood of locating an appropriate HLA matched unrelated donor through the various donor registries is limited.
Stem cells from partially HLA matched family members (also called haploidentical transplant) is an option currently being explored for this patient population. This type of transplant has been used and found to be successful in some patients, mostly those with cancers of the blood. However, there can be significant complications with haploidentical transplant, primarily infection, failure of the graft to grow (graft failure), and a disorder called graft-versus-host disease. In addition, few patients with sickle cell disease have undergone this procedure. Therefore, the risks and benefits of haploidentical transplants for patients with sickle cell disorder are not as well established as those using an HLA identical sibling or unrelated donor.
The primary objective of this study is to assess the safety of haploidentical stem cell transplantation for children and adolescents with severe sickle cell disease and stroke or abnormal transcranial Doppler ultrasound requiring chronic transfusion therapy. The treatment plan will be considered safe if there is not excessive toxicity. Toxicity for this protocol is defined as graft failure/graft rejection, severe acute GVHD, or regimen related death within 100 days after the last cellular product administered.
Of note, the protocol was closed to accrual in September 2007 as we had met the stopping rules related to graft integrity (graft failure and graft rejection). Participants currently enrolled continue to be followed per protocol.
Detailed description
Secondary objectives for this protocol include the following:
- To estimate 1-year overall and event free survival after transplantation. An event is defined as toxicity (graft failure, death, grade III/IV acute GHVD), or a sickle-related event (stroke, acute chest syndrome, pain crisis).
- To obtain preliminary information regarding donor engraftment among different cell subsets, including unsorted mononuclear cell, and lymphoid fractions during the first year after transplant.
- To observe the rate of acute and chronic GVHD during the first year after transplant.
- To assess the proportion of research participants who experience poor graft integrity and therefore require additional donor stem cells or lymphocytes.
- To document the effect of stem cell transplant on the central nervous system as defined by radiological imaging and neuropsychological testing.
- To investigate immune reconstitution 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: Hematopoietic Stem Cell Transplantation, Device: CliniMACS, Drug: See intervention description |
Who may qualify
- Ages
- 2 to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Hemoglobin SS or S-Beta Thalassemia Sickle Cell Disease.
- Partially-matched family member with hemoglobin AA (normal) or hemoglobin AS (sickle trait) phenotype.
- Stroke (persistent neurologic deficit lasting > 24 hours and present on MRI) or abnormal transcranial Doppler (TCD) ultrasonography requiring chronic transfusion therapy. A TCD is deemed abnormal when the velocity is greater than or equal to 200 cm/sec. Chronic transfusion therapy is defined as "packed red blood cell transfusions administered approximately every 3-5 weeks to decrease the percentage of sickle hemoglobin (Hemoglobin S) to prevent complications of sickle cell disease. This is used most commonly to treat/prevent stroke, acute chest syndrome, and/or pain crises.
Key exclusion criteria (8 listed)
- Karnofsky or Lansky score < 60%
- Acute hepatitis or evidence of moderate or severe portal fibrosis on biopsy. (Biopsy will be obtained if patient on chronic transfusion therapy > 6 months or ferritin > 1000 ng/ml) International normalized ratio (INR) less than 2 times normal. ALT and AST less than 3 times the upper limit of normal.
- Severe renal impairment (as evidenced by GFR < 30% predicted normal)
- Ejection fraction or shortening fraction below lower limit of normal for age.
- Pregnancy
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 |
|---|---|---|
| Hematopoietic Stem Cell TransplantationAllogeneic stem cell transplant Haploidentical stem cell transplant Mismatched family member donor stem cell transplant T cell selection CD34 enrichment | Procedure or surgery | 1 |
| CliniMACS | Device | 1 |
| See intervention descriptionHydroxyurea and azathioprine were administered for a 3 month period prior to the initiation of the transplant procedure in an effort to help prevent rejection of the donor product. Approximately 10 days prior to the transplant procedure, all participants received the same preparative regimen consisting of Busulfan, cyclophosphamide, low-dose thiotepa, and OKT3. MMF was administered for GVHD prophylaxis. Two separate infusions of donor stem cells were administered with fixed doses of CD3 and CD34 cells. These haploidentical stem cells were processed using the investigational CliniMACS device. | Drug | 1 |
Primary outcome
To assess the safety of haploidentical stem cell transplantation for children and adolescents with severe sickle cell disease and stroke or abnormal transcranial Doppler ultrasound requiring chronic transfusion therapy.
Time frame: September 2007
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2017.
- Derived from this study: PubMed 23416852Dallas MH, Triplett B, Shook DR, Hartford C, Srinivasan A, Laver J, Ware R, Leung W. Long-term outcome and evaluation of organ function in pediatric patients undergoing haploidentical and matched related hematopoietic cell transplantation for sickle cell disease. Biol Blood Marrow Transplant. 2013 May;19(5):820-30. doi: 10.1016/j.bbmt.2013.02.010. Epub 2013 Feb 14.
- St. Jude Children's Research HospitalLink provided by the sponsor.
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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.
Wing Leung, M.D. 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 Phase 1 study testing Hematopoietic Stem Cell Transplantation, CliniMACS and See intervention description in people with Sickle Cell Disease, 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 3 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 26 Apr 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To assess the safety of haploidentical stem cell transplantation for children and adolescents with severe sickle cell disease and stroke or abnormal transcranial Doppler ultrasound requiring chronic transfusion therapy. (time frame: September 2007). 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 NCT00152113, 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 26 Apr 2017; AzTrials last refreshed its copy on 6 Nov 2026.