Sickle Cell DiseaseNCT04207320
Haploidentical Hematopoietic Stem Cell Transplantation (HSCT) for Patients With Severe Sickle Cell Disease
A study testing αβ+ T-cell depletion with Miltenyi CliniMACS system in people with Sickle Cell Disease, run by University of Chicago at 1 site in United States.
Trial summary
The purpose of this study is to develop a safe and curative stem cell transplant approach to treating sickle cell disease by assessing the safety of haploidentical hematopoietic stem cell transplantation using αβ+ T-cell depletion for children and adolescents with severe sickle cell disease (SCD). Read more about this study
- Who is it for?
- Ages 2 to 25 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- αβ+ T-cell depletion with Miltenyi CliniMACS system
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Apr 2020to 22 May 2023
- Phase
- Interventional
- 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 2 to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Hemoglobin SS, SC, S-β0 Thalassemia, or SO-Arab Sickle Cell Disease
- Between the ages of 2 and 25 years (Stage 1: 10-25 years; Stage II: 2-25 years)
- Lack a fully matched family donor or fully matched unrelated donor register in the National Marrow Donor Program
- Partially-matched family member with hemoglobin AA (normal) or hemoglobin AS (sickle trait) phenotype
- SCD with Severe Phenotype, defined by the following criteria: Neurologic manifestations of sickle disease including cerebral vascular accident (CVA), transient ischemic event (TIA) or abnormal MRI findings suggestive of silent infarct; Two or more episodes of acute chest syndrome (ACS) requiring admission for transfusional or respiratory support including supplemental oxygen within [two years] of enrollment in study despite hydroxyurea therapy. Patients who cannot tolerate hydroxyurea and who experience multiple episodes of ACS will also be eligible; History of severe vaso-occlusive (VOC) disease requiring hospitalization and intravenous narcotics on 3 or more occasions per year over the two years prior to enrollment despite hydroxyurea therapy. Patients who cannot tolerate hydroxyurea and who experience multiple episodes of VOC will also be eligible; Other severe phenotype as evidenced by end organ dysfunction related to sickle cell disease.
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 has been on chronic transfusion therapy > 6 months or has a ferritin > 1000 ng/ml) or AST or ALT >5 times the upper limit of normal
- Severe renal impairment (as evidenced by creatinine clearance of <50ml/minute glomerular filtration rate (GFR) < 50% predicted normal)
- Cardiac function that demonstrates shortening fraction less than 26% by cardiac echocardiogram or pulmonary hypertension.
- Pregnant Female.
- Lactating female.
- Pulmonary function with baseline O2 saturation <85% or Diffusing Capacity for Carbon Monoxide (DLCO) on pulmonary function testing (PFT) with a DLCO <40%.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Hematopoietic Stem Cell Transplantation for Patients With Severe Sickle Cell Disease Using Myeloablative Conditioning and αβ+ T-cell Depleted Hematopoietic Stem Cells From Partially Matched Familial Donors
The purpose of this study is to develop a safe and curative stem cell transplant approach to treating sickle cell disease by assessing the safety of haploidentical hematopoietic stem cell transplantation using αβ+ T-cell depletion for children and adolescents with severe sickle cell disease (SCD).
- Conditions
- Sickle Cell Disease
- Being tested
- αβ+ T-cell depletion with Miltenyi CliniMACS system
- 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.
αβ+ T-cell depletion with Miltenyi CliniMACS systemDevice
Haploidentical CD34+ megadose hematopoietic stem cell transplant in which cells are purified using the Miltenyi CliniMACS system designed for αβ+ T-cell receptor selection using immunomagnetic beads.
| Study group | Role | What they receive |
|---|---|---|
| Stage I | Experimental | Stage I will include eligible subjects between the ages of 10-25 years. Receives: Device: αβ+ T-cell depletion with Miltenyi CliniMACS system |
| Stage II | Experimental | Stage II will include eligible subjects between the ages of 2-25 years. Receives: Device: αβ+ T-cell depletion with Miltenyi CliniMACS system |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety, as Measured by Incidence of Graft Failure, Grade III/IV Irreversible End Organ Toxicity, Grade III/IV aGvHD, or Death Within 100 Days Post-Hap-HSCT
Graft Function: efficacy is defined as stable donor engraftment (>5% total nucleated cell DNA) and donor erythropoiesis that corrects the SCD hematologic phenotype (<50% HbS in the peripheral blood).
Organ Toxicity: grade III/IV irreversible end organ toxicity based on NCI grading
Graft Versus Host disease: grade III/IV aGvHD or death within 100 days post- Hap-HSCT
Measured: 100 days post-Hap-HSCT
Secondary outcomes (5)
Estimate 1-year Overall and Event-free Survival After Hap-HSCT
Proportion of patients at 1 year who have not died or had graft failure
Measured: 1 year post transplant
Observe the Incidence of Grades I Through IV Acute GvHD
Proportion of subjects with grades I through IV acute GvHD
Measured: 100 days post transplant
Observe Incidence of Severe Acute GvHD as Defined by Grades III Through IV
Proportion of subjects with grades III through IV acute GvHD
Measured: 100 days post transplant
Observe the Incidence of Grades I Through IV Chronic GvHD
Proportion of subjects with grades I through IV chronic GvHD
Measured: 1 year post transplant
Observe Incidence of Severe Chronic GvHD as Defined by Grades III and IV
Proportion of subjects with grades III through IV chronic GvHD
Measured: 1 year post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2019
- Study start7 Apr 2020
- Primary completion22 May 2023
- Study completion22 May 2023
Why it stopped: Study terminated by PI
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 Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by University of ChicagoThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- John Cunningham, MD, Principal investigator, University of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04207320
- Sponsor's protocol ID
- IRB19-0640
- Status last verified
- Nov 2024
- First submitted
- 11 Dec 2019
- Last updated
- 4 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hematopoietic Stem Cell Transplantation for Patients With Severe Sickle Cell Disease Using Myeloablative Conditioning and αβ+ T-cell Depleted Hematopoietic Stem Cells From Partially Matched Familial Donors
- ClinicalTrials.gov ID
- NCT04207320
- Acronym / sponsor ID
- IRB19-0640
- Conditions
- Sickle Cell Disease
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study terminated by PI
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Study start
- 7 Apr 2020 (actual)
- Primary completion
- 22 May 2023 (actual)
- Study completion
- 22 May 2023 (actual)
- First posted
- 20 Dec 2019 (actual)
- Results
- Posted 4 Dec 2024
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 study is to develop a safe and curative stem cell transplant approach to treating sickle cell disease by assessing the safety of haploidentical hematopoietic stem cell transplantation using αβ+ T-cell depletion for children and adolescents with severe sickle cell disease (SCD).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Stage I | Experimental | Device: αβ+ T-cell depletion with Miltenyi CliniMACS systemStage I will include eligible subjects between the ages of 10-25 years. |
| Stage II | Experimental | Device: αβ+ T-cell depletion with Miltenyi CliniMACS systemStage II will include eligible subjects between the ages of 2-25 years. |
Who may qualify
- Ages
- 2 to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Hemoglobin SS, SC, S-β0 Thalassemia, or SO-Arab Sickle Cell Disease
- Between the ages of 2 and 25 years (Stage 1: 10-25 years; Stage II: 2-25 years)
- Lack a fully matched family donor or fully matched unrelated donor register in the National Marrow Donor Program
- Partially-matched family member with hemoglobin AA (normal) or hemoglobin AS (sickle trait) phenotype
- SCD with Severe Phenotype, defined by the following criteria: Neurologic manifestations of sickle disease including cerebral vascular accident (CVA), transient ischemic event (TIA) or abnormal MRI findings suggestive of silent infarct; Two or more episodes of acute chest syndrome (ACS) requiring admission for transfusional or respiratory support including supplemental oxygen within [two years] of enrollment in study despite hydroxyurea therapy. Patients who cannot tolerate hydroxyurea and who experience multiple episodes of ACS will also be eligible; History of severe vaso-occlusive (VOC) disease requiring hospitalization and intravenous narcotics on 3 or more occasions per year over the two years prior to enrollment despite hydroxyurea therapy. Patients who cannot tolerate hydroxyurea and who experience multiple episodes of VOC will also be eligible; Other severe phenotype as evidenced by end organ dysfunction related to sickle cell disease.
Key exclusion criteria (7 listed)
- Karnofsky or Lansky score < 60%
- Acute hepatitis or evidence of moderate or severe portal fibrosis on biopsy. (Biopsy will be obtained if patient has been on chronic transfusion therapy > 6 months or has a ferritin > 1000 ng/ml) or AST or ALT >5 times the upper limit of normal
- Severe renal impairment (as evidenced by creatinine clearance of <50ml/minute glomerular filtration rate (GFR) < 50% predicted normal)
- Cardiac function that demonstrates shortening fraction less than 26% by cardiac echocardiogram or pulmonary hypertension.
- Pregnant Female.
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 |
|---|---|---|
| αβ+ T-cell depletion with Miltenyi CliniMACS systemHaploidentical CD34+ megadose hematopoietic stem cell transplant in which cells are purified using the Miltenyi CliniMACS system designed for αβ+ T-cell receptor selection using immunomagnetic beads. | Device | Stage I, Stage II |
Primary outcome
Safety, as Measured by Incidence of Graft Failure, Grade III/IV Irreversible End Organ Toxicity, Grade III/IV aGvHD, or Death Within 100 Days Post-Hap-HSCT
Time frame: 100 days post-Hap-HSCT
Graft Function: efficacy is defined as stable donor engraftment (>5% total nucleated cell DNA) and donor erythropoiesis that corrects the SCD hematologic phenotype (<50% HbS in the peripheral blood). Organ Toxicity: grade III/IV irreversible end organ toxicity based on NCI grading Graft Versus Host disease: grade III/IV aGvHD or death within 100 days post- Hap-HSCT
5 secondary outcomes
Estimate 1-year Overall and Event-free Survival After Hap-HSCT
Time frame: 1 year post transplant
Observe the Incidence of Grades I Through IV Acute GvHD
Time frame: 100 days post transplant
Observe Incidence of Severe Acute GvHD as Defined by Grades III Through IV
Time frame: 100 days post transplant
Observe the Incidence of Grades I Through IV Chronic GvHD
Time frame: 1 year post transplant
Observe Incidence of Severe Chronic GvHD as Defined by Grades III and IV
Time frame: 1 year post transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
John Cunningham, MD principal investigator
University of Chicago
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing αβ+ T-cell depletion with Miltenyi CliniMACS system in people with Sickle Cell Disease, run by University of Chicago 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 5 inclusion and 7 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 4 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Dec 2024). 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?
Safety, as Measured by Incidence of Graft Failure, Grade III/IV Irreversible End Organ Toxicity, Grade III/IV aGvHD, or Death Within 100 Days Post-Hap-HSCT (time frame: 100 days post-Hap-HSCT). 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 4 Dec 2024.