Sickle Cell-thalassemia DiseasePhase 1NCT02165007
Haploidentical Hematopoietic Stem Cell Transplantation
A Phase 1 study testing peripheral blood stem cell graft that are CD34+ selected in people with Sickle Cell-thalassemia Disease and Thalassemia, run by Catherine Bollard at 1 site in United States.
Trial summary
The study is designed as a Pilot/Phase 1 trial of reduced intensity Haploidentical HSCT in patients with sickle cell disease and thalassemia. The purpose of the study is to assess the safety and toxicity of reduced intensity conditioning haploidentical hematopoietic stem cell transplantation. Read more about this study
- Who is it for?
- Ages Up to 22 years
- Conditions the study is for
- Sickle Cell-thalassemia Disease, Thalassemia
- What is being tested?
- peripheral blood stem cell graft that are CD34+ selected
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2015to Oct 2024
- 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 Up to 22 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- First allogeneic transplant
- Age up to 22 years
- Patients with severe sickle cell disease (stroke, elevated TCD velocities, >2 acute chest syndrome, ongoing chronic red cell transfusion > 6 months)
- Patients with transfusion dependent thalassemia and evidence of iron overload
- Patients must have a related donor that is HLA-matched at >/=4 of 8 but <8/8 HLA-A, -B, -C and -DRB1
- Cardiac function: Shortening fraction >25%; ejection fraction >40%
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- Estimated creatinine clearance greater than 50 mL/minute
- Pulmonary function: DLCO ≥40% (adjusted for hemoglobin) and FEV1≥50% in patients 7 years and older with normal cognitive function and able to perform the test adequately. If not able to complete the testing a CT chest will be required., oxygen saturation>91%
- Liver function: direct (conjugated) bilirubin < 2x the upper limit of normal and ALT/AST < 2.5x the upper normal limit.
- Signed informed consent.
Who cannot join
- Life expectancy less than 6 months
- Patients with uncontrolled bacterial, viral or fungal infections (undergoing appropriate treatment and with progression of clinical symptoms) within 1 month prior to conditioning. Patients with febrile illness or suspected minor infection should await clinical resolution prior to starting conditioning.
- Pregnant or breastfeeding patients
- Patients seropositive for the human immunodeficiency virus (HIV)
- Patient with active Hepatitis B or C determined by serology and/or NAAT
- Active hepatitis, bridging fibrosis or cirrhosis on liver biopsy (biopsy required for patients on chronic transfusion therapy for > 1 year and evidence of iron overload with ferritin >1000 ng/mL)
- Patients with suitable 8/8 HLA matched related and unrelated donors
- Patients who have an intolerance to or have received alemtuzumab in the prior 6 months will be excluded from enrollment unless alemtuzumab is replaced with rabbit ATG in the conditioning regimen
Trial locations and contacts
1 site in 1 country.
United States1 site
Childrens National Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR CHILDREN WITH SICKLE CELL DISEASE AND THALASSEMIA USING CD34+ POSITIVE SELECTED GRAFTS
The study is designed as a Pilot/Phase 1 trial of reduced intensity Haploidentical HSCT in patients with sickle cell disease and thalassemia. The purpose of the study is to assess the safety and toxicity of reduced intensity conditioning haploidentical hematopoietic stem cell transplantation.
Read the detailed description
Research subjects will undergo reduced intensity conditioning (Hydroxyurea, ATG, Fludarabine, Thiotepa, Melphalan) followed by infusion of a peripheral blood stem cell graft collected from haploidentical family donors that are CD34+ positively selected using the CliniMACS device. Sirolimus will be used for GVHD prophylaxis and given for 9 months post-transplant and then tapered off by one year
The use of the CliniMACS device for CD34 selection will be performed at CNMC through cross-reference of the master file for CliniMACS CD34+ Reagent by Milteyni Biotech (BB-MF 8061).
CliniMACs is an electromechanical device intended to isolate certain cell subsets from mixed cell populations. When used in combination with the CliniMACs CD34 reagent, it is possible to prepare extremely pure populations of CD34+ cells with upwards of 5 logs depletion of contaminating T cells within a closed and sterile system.
We intend to use this system to select cells from HLA haploidentical related donors who have been mobilized with G-CSF prior to stem cell collection. Since previous investigations of this strategy in adult patients have not translated into enhanced long term survival, we intend to limit this protocol to patients under the age of 22 as they have more rapid immune reconstitution.
- Conditions
- Sickle Cell-thalassemia Disease, Thalassemia
- Being tested
- peripheral blood stem cell graft that are CD34+ selected
- Medical subject headings
- Thalassemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
peripheral blood stem cell graft that are CD34+ selectedDrug
Also called Reduced intensity conditioning, Sirolimus
The preparatory regimen will consist of Hydroxyurea from Days -50 to -22, Alemtuzumab from days -21 to -19 (test dose Alemtuzumab on day -22), Fludarabine days -8 to -4, Thiotepa Day -4, Melphalan day -3 to -2 (Table 4a). In patients with intolerance to or have received alemtuzumab in the prior 6 months, alemtuzumab will be replaced with rabbit ATG on days -10 through -7, followed by infusion of a peripheral blood stem cell graft collected from haploidentical family donors that are CD34+ positively selected using the CliniMACS device. Sirolimus will be used for GVHD prophylaxis and given for 9 months post-transplant and then tapered off by one year.
| Study group | Role | What they receive |
|---|---|---|
| peripheral blood stem cell graft that are CD34+ selected | Experimental | peripheral blood stem cell graft that are CD34+ selected. All patients will undergo reduced intensity conditioning regimen which followed by infusion of a peripheral blood stem cell graft collected from haploidentical family donors that are CD34+ positively selected using the CliniMACS device and Sirolimus will be used for GVHD prophylaxis and given for 9 months post-transplant and then tapered off by one year (see intervention). Receives: Drug: peripheral blood stem cell graft that are CD34+ selected |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of transplant related adverse outcomes
The primary endpoint of this trial is safety. Transplant related adverse outcomes and non-hematological toxicity will be measured through Day +60 on this objective to include:
- Non-hematological severe (Grade IV and V) organ specific toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0)
- Rates of non-engraftment
- Severe acute (Grade III-IV)
- Veno-occlusive disease of the liver
- Idiopathic pneumonia syndrome
- Seizures/Posterior reversible encephalopathy syndrome (PRES)
Measured: 60 days
Secondary outcomes (1)
Overall survival
Overall survival upto 2 years
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2014 (estimated)
- Study startJan 2015
- Primary completionJan 2024
- Study completionOct 2024
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-thalassemia DiseaseStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Catherine Bollard
- Sponsor type
- University, hospital or other
- Collaborators
- Children's National Research Institute
- Responsible party
- Sponsor-investigator, Catherine Bollard, Children's National Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02165007
- Sponsor's protocol ID
- HAPSICKLE
- Status last verified
- Dec 2024
- First submitted
- 13 Jun 2014
- Last updated
- 19 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Leonard A, Furstenau D, Abraham A, Darbari DS, Nickel RS, Limerick E, Fitzhugh C, Hsieh M, Tisdale JF. Reduction in vaso-occlusive events following stem cell transplantation in patients with sickle cell disease. Blood Adv. 2023 Jan 24;7(2):227-234. doi: 10.1182/bloodadvances.2022008137.
PubMed 36240296
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR CHILDREN WITH SICKLE CELL DISEASE AND THALASSEMIA USING CD34+ POSITIVE SELECTED GRAFTS
- ClinicalTrials.gov ID
- NCT02165007
- Acronym / sponsor ID
- HAPSICKLE
- Conditions
- Sickle Cell-thalassemia Disease, Thalassemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Catherine BollardUniversity, hospital or other
- Collaborators
- Children's National Research Institute
- Study start
- Jan 2015
- Primary completion
- Jan 2024 (actual)
- Study completion
- Oct 2024 (actual)
- First posted
- 17 Jun 2014 (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.
The study is designed as a Pilot/Phase 1 trial of reduced intensity Haploidentical HSCT in patients with sickle cell disease and thalassemia. The purpose of the study is to assess the safety and toxicity of reduced intensity conditioning haploidentical hematopoietic stem cell transplantation.
Detailed description
Research subjects will undergo reduced intensity conditioning (Hydroxyurea, ATG, Fludarabine, Thiotepa, Melphalan) followed by infusion of a peripheral blood stem cell graft collected from haploidentical family donors that are CD34+ positively selected using the CliniMACS device. Sirolimus will be used for GVHD prophylaxis and given for 9 months post-transplant and then tapered off by one year
The use of the CliniMACS device for CD34 selection will be performed at CNMC through cross-reference of the master file for CliniMACS CD34+ Reagent by Milteyni Biotech (BB-MF 8061).
CliniMACs is an electromechanical device intended to isolate certain cell subsets from mixed cell populations. When used in combination with the CliniMACs CD34 reagent, it is possible to prepare extremely pure populations of CD34+ cells with upwards of 5 logs depletion of contaminating T cells within a closed and sterile system.
We intend to use this system to select cells from HLA haploidentical related donors who have been mobilized with G-CSF prior to stem cell collection. Since previous investigations of this strategy in adult patients have not translated into enhanced long term survival, we intend to limit this protocol to patients under the age of 22 as they have more rapid immune reconstitution.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| peripheral blood stem cell graft that are CD34+ selected | Experimental | Drug: peripheral blood stem cell graft that are CD34+ selectedperipheral blood stem cell graft that are CD34+ selected. All patients will undergo reduced intensity conditioning regimen which followed by infusion of a peripheral blood stem cell graft collected from haploidentical family donors that are CD34+ positively selected using the CliniMACS device and Sirolimus will be used for GVHD prophylaxis and given for 9 months post-transplant and then tapered off by one year (see intervention). |
Who may qualify
- Ages
- Up to 22 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- First allogeneic transplant
- Age up to 22 years
- Patients with severe sickle cell disease (stroke, elevated TCD velocities, >2 acute chest syndrome, ongoing chronic red cell transfusion > 6 months)
- Patients with transfusion dependent thalassemia and evidence of iron overload
- Patients must have a related donor that is HLA-matched at >/=4 of 8 but <8/8 HLA-A, -B, -C and -DRB1
Key exclusion criteria (8 listed)
- Life expectancy less than 6 months
- Patients with uncontrolled bacterial, viral or fungal infections (undergoing appropriate treatment and with progression of clinical symptoms) within 1 month prior to conditioning. Patients with febrile illness or suspected minor infection should await clinical resolution prior to starting conditioning.
- Pregnant or breastfeeding patients
- Patients seropositive for the human immunodeficiency virus (HIV)
- Patient with active Hepatitis B or C determined by serology and/or NAAT
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 |
|---|---|---|
| peripheral blood stem cell graft that are CD34+ selectedAlso: Reduced intensity conditioning, SirolimusThe preparatory regimen will consist of Hydroxyurea from Days -50 to -22, Alemtuzumab from days -21 to -19 (test dose Alemtuzumab on day -22), Fludarabine days -8 to -4, Thiotepa Day -4, Melphalan day -3 to -2 (Table 4a). In patients with intolerance to or have received alemtuzumab in the prior 6 months, alemtuzumab will be replaced with rabbit ATG on days -10 through -7, followed by infusion of a peripheral blood stem cell graft collected from haploidentical family donors that are CD34+ positively selected using the CliniMACS device. Sirolimus will be used for GVHD prophylaxis and given for 9 months post-transplant and then tapered off by one year. | Drug | peripheral blood stem cell graft that are CD34+ selected |
Primary outcome
Incidence of transplant related adverse outcomes
Time frame: 60 days
The primary endpoint of this trial is safety. Transplant related adverse outcomes and non-hematological toxicity will be measured through Day +60 on this objective to include: * Non-hematological severe (Grade IV and V) organ specific toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0) * Rates of non-engraftment * Severe acute (Grade III-IV) * Veno-occlusive disease of the liver * Idiopathic pneumonia syndrome * Seizures/Posterior reversible encephalopathy syndrome (PRES)
1 secondary outcome
Overall survival
Time frame: 2 years
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 19 Dec 2024.
- Derived from this study: PubMed 36240296Leonard A, Furstenau D, Abraham A, Darbari DS, Nickel RS, Limerick E, Fitzhugh C, Hsieh M, Tisdale JF. Reduction in vaso-occlusive events following stem cell transplantation in patients with sickle cell disease. Blood Adv. 2023 Jan 24;7(2):227-234. doi: 10.1182/bloodadvances.2022008137.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 peripheral blood stem cell graft that are CD34+ selected in people with Sickle Cell-thalassemia Disease and Thalassemia, run by Catherine Bollard 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 10 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 19 Dec 2024. 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?
Incidence of transplant related adverse outcomes (time frame: 60 days). 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 NCT02165007, 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 19 Dec 2024; AzTrials last refreshed its copy on 30 Oct 2026.