Sickle Cell DiseasePhase 1/2NCT07599176
Partial Stem Cell Transplant for Sickle Cell Disease From Matched Donors
A Phase 1/2 study testing Total Body Irradiation, Alemtuzumab and Abatacept in people with Sickle Cell Disease and Beta-thalassemia, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
This is a non-ablative (partial) stem cell transplant for patients with severe sickle cell disease or beta-thalassemia requiring red cell transfusions. The intensity of the transplant is slightly increased from our previous transplant regimens. Read more about this study
- Who is it for?
- Ages 4 to 65 years
- Conditions the study is for
- Sickle Cell Disease, Beta-thalassemia
- What is being tested?
- Total Body Irradiation, Alemtuzumab and Abatacept
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Jul 2026to 30 Jun 2035
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 4 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- RECIPIENT:
- Participants must fulfill one disease category (1 or 2) and 3
- Patients with sickle cell disease at high risk for disease related morbidity or mortality, defined by having an end-organ damage (A, B, C, D, OR E) or complication(s) not ameliorated by sickle cell-specific therapies (F):
- Stroke defined as a clinically significant neurologic event that is accompanied by an infarct on cerebral MRI ORb
- Abnormal trans-cranial Doppler examination (>=200 cm/s); OR
- Silent cerebral infarct defined as an infarct-like lesion based on an MRI signal abnormality at least 3 mm in one dimension and visible in two planes on FLAIR or T2- weighted images (or similar image with 3D imaging) and documented neurological examination performed by a neurologist demonstrating the participant has a normal neurologic examination, or an abnormality on examination that could not be explained by the location of the brain lesion(s); OR
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- Sickle cell related renal insufficiency defined by a creatinine level >=1.5 times the upper limit of normal and kidney biopsy consistent with sickle cell nephropathy OR nephrotic syndrome OR creatinine clearance <60mL/min/1.73m2 for patients <16 years of age or <50mL/min for patients >16 years of age OR requiring peritoneal or hemodialysis; OR
- Age (Years): <= 5 / Upper limit of normal serum creatinine (mg/dl): 0.8
- Age (Years): 5 < age <= 10 / Upper limit of normal serum creatinine (mg/dl): 1.0
- Age (Years): 10 < age <= 15 / Upper limit of normal serum creatinine (mg/dl): 1.2
- Age (Years): > 15 / Upper limit of normal serum creatinine (mg/dl): 1.3
- Tricuspid regurgitant jet velocity (TRV) of >=2.5 m/s in patients at least 3 weeks after a vaso-occlusive crisis; OR
- Recurrent severe priapism defined as at least two episodes of an erection lasting >=4 hours requiring medical intervention (e.g. aspiration, injection of vasoconstrictor, prior penile surgery.); OR
- Sickle hepatopathy defined as EITHER ferritin >1000mcg/L OR direct bilirubin >0.4 mg/dL at baseline; OR
- Vaso-occlusive crises: more than 1 hospital admission per year while on a therapeutic dose of sickle cell treatment /medication; OR
- Acute chest syndrome (ACS): any ACS while on sickle cell treatment /medication
- Patients with beta-thalassemia who have grade 2 or 3 iron overload, determined by the presence of 2 or more of the following:
- Portal fibrosis by liver biopsy
- Inadequate chelation history (defined as failure to maintain adequate compliance with chelation with deferoxamine initiated within 18 months of the first transfusion and administered at least 5 days each week)
- Hepatomegaly of greater than 2 cm below the costochondral margin or by other imaging scans
- Non disease specific
- Ages >=4 years and less than 65 years old
- Fully matched human leukocyte antigen (HLA) donors at A, B, C, and DR loci (8 of 8 or 10 of 10)
- Ability to comprehend and willing to sign an informed consent, assent obtained from minors when applicable. Negative serum or urine beta-HCG, when applicable
- Agree to use birth control throughout the study and 3 months after abatacept or sirolimus administration.
- Female subjects must agree to use a medically acceptable method of birth control such as oral contraceptive, intrauterine device, barrier and spermicide, or implant/injection from start of screening until immunosuppression is stopped.
- Male subjects must agree to use effective contraception (including condoms) from start of screening until immunosuppression is stopped.
- DONOR:
- Fully matched human leukocyte antigen (HLA) donors at A, B, C, and DR loci (8 of 8 or 10 of 10) are intended for this study.
- Donors age 4 or older and >=15 kg (or weight deemed acceptable by IR for line placement, DTM for apheresis, and pediatric consult service) eligible to donate hematopoietic stem cells, are eligible for this study.
- Donors will be evaluated in accordance with existing Standard NIH Policies and Procedures for determination of eligibility and suitability for clinical donation. Donors will sign on a separate protocol, 20-H-0099 NHLBI standard of care protocol for the mobilization and collection of HSCs. Note that participation in this study is offered to all eligible donors, but is not required for a donor to make a stem cell donation, so it is possible that not all donors will enroll onto this study.
Who cannot join
- RECIPIENT:
- Karnofsky or Lanksy performance status of <40
- Diffusing capacity of carbon monoxide <35% predicted: DLCO corrected for hemoglobin or KCO (corrected for lung volume). This criterion may be omitted in young children (e.g. near age 5) or other individuals who may have difficulty understanding or complying with instructions of testing.
- Baseline oxygen saturation of <85% or PaO2 <70
- Left ventricular ejection fraction: <35% estimated by ECHO
- Transaminases >5x upper limit of normal for age
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- Evidence of uncontrolled bacterial, viral, or fungal infections (currently taking medication and progression of clinical symptoms) within one month prior to starting the conditioning regimen
- Major anticipated illness or organ failure incompatible with survival from HCT
- Pregnant or breastfeeding
- DONOR:
- Pregnant or breastfeeding
- Cognitively impaired subjects
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
NIH Clinical Center Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
Official title: Matched Related Donor Non-myeloablative Hematopoietic Cell Transplantation With Alemtuzumab, 400 cGy TBI, and Abatacept for Sickle Cell Disease and Beta-Thalassemia
This is a non-ablative (partial) stem cell transplant for patients with severe sickle cell disease or beta-thalassemia requiring red cell transfusions. The intensity of the transplant is slightly increased from our previous transplant regimens. The goal is to aim for higher percentage of donor cells to stably remain in the recipients long term.
Read the detailed description
Study Description:
Our prior non-myeloablative conditioning regimen (03H0170) included 1mg/kg of alemtuzumab divided over 5 days, 300 cGy total body irradiation (TBI), and sirolimus for immune suppression. Sickle disease-free survival (DFS) and overall survival (OS) were 85% and 94% respectively, graft failure 15%, no transplant related mortality (TRM), and acute or chronic GVHD <5%. A large proportion of patients achieved robust (>=95%) donor myeloid chimerism at day 30, but this proportion decreased quickly to 67.2% at 1, 64.9% at 2, and 60% at 3, and 56.9% at 4 years post-transplant.
A subsequent protocol (000539H) added briquilimab, an antibody targeting CD117 (c-Kit), to alem-300 cGy TBI regimen, but did not reduce the gradual decline in donor myeloid chimerism as originally hypothesized, leading to protocol closure. Rates of graft failure was 20%, no TRM, acute GVHD was 5%, and no chronic GVHD. We now propose to increase TBI to 400 cGy to further deplete host lymphoid and myeloid cells to achieve a higher percentage of donor leukocyte engraftment without substantially increasing toxicity. Since we will continue to use filgrastim to mobilize and collect donor hematopoietic cells, we also add abatacept to preserve the low rates of GVHD.
Objectives:
Primary Objective:
To reduce the proportion of patients with graft failure or donor myeloid chimerism <95%
Secondary Objectives:
- To compare CD14/15 and CD3 chimerism to prior MRD HCT protocols (03-H-0170, 14-H-0077, and 000539H)
- To assess the usual transplant related parameters, such as count recovery, transfusion support, rates of GVHD, viral/bacterial infections, rates of transplant related and overall mortality, and compare to prior MRD HCT protocols
Tertiary Objectives:
- To compare changes in organ function
- To examine neuropsychological functioning, wellbeing, and pain before and after HCT
- To obtain reproductive health related changes before and after HCT
Endpoints:
Primary Endpoint: proportion of participants with graft failure or myeloid chimerism <95% at 1 year post HCT
Secondary Endpoints:
- Percent myeloid (CD14/15) chimerism at day 30, 60, 100, 1 year, 2 years, and 3 years post HCT
- Percent T cell (CD3) chimerism at day 30, 60, 100, 1 year, 2 years, and 3 years post HCT
- Day of neutrophil engraftment per CIBMTR definition
- Day of platelet engraftment per CIBMTR definition
- Rates of viral reactivation or infection to day 100 post HCT
- Rates of acute and chronic GVHD at 1 and 2 years post HCT, respectively
- Rates of graft failure or myeloid chimerism <95% at 1 year post HCT
- Transplant related mortality at 1, 2, and 3 years post HCT
- Non-transplant related mortality at 1, 2 and 3 years post HCT
Exploratory Endpoints:
-Quality of life, neuropsychologic function, reproductive health questionnaires, serial testing or imaging of organ function/status
- Conditions
- Sickle Cell Disease, Beta-thalassemia
- Being tested
- Total Body Irradiation, Alemtuzumab, Abatacept, Research blood draw
- Keywords
- Sickle Cell Disease, Beta-Thalassemia, Stem Cell Transplant, Chimerism
- Medical subject headings
- Anemia, Sickle Cell, beta-Thalassemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Total Body IrradiationRadiation
Total Body Irradiation 400 cGy
AlemtuzumabDrug
1 mg/kg
AbataceptDrug
10 mg/kg x 6
Research blood drawOther
About 5 tablespoons of blood will be collected from donors for research purposes.
| Study group | Role | What they receive |
|---|---|---|
| Matched related donors | Other | Donors for patients Receives: Other: Research blood draw |
| Transplant recipients | Experimental | Patients with symptomatic sickle cell disease or beta-thalassemia Receives: Radiation: Total Body Irradiation; Drug: Alemtuzumab; Drug: Abatacept; Other: Research blood draw |
What is being measured
The primary outcome is the main question the study is designed to answer.
Donor myeloid chimerism
percentage of donor myeloid chimerism
Measured: 1 year
Secondary outcomes (3)
Donor CD3 chimerism
percentage of donor myeloid chimerism
Measured: 1 year
Overall survival
percentage of patients surviving at 1 year
Measured: 1 year
Acute Graft versus Host Disease
percentage of patients with Grade 2-4 acute GVHD
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 posted20 May 2026
- Study start8 Jul 2026
- Primary completion30 Jun 2032 (estimated)
- Study completion30 Jun 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- John F Tisdale, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07599176
- Sponsor's protocol ID
- 10002545
- Other IDs
- 002545-H
- Status last verified
- 9 Oct 2026
- First submitted
- 16 May 2026
- Last updated
- 13 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: We are planning to collect and report data as a group.
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Matched Related Donor Non-myeloablative Hematopoietic Cell Transplantation With Alemtuzumab, 400 cGy TBI, and Abatacept for Sickle Cell Disease and Beta-Thalassemia
- ClinicalTrials.gov ID
- NCT07599176
- Acronym / sponsor ID
- 10002545
- Conditions
- Sickle Cell Disease, Beta-thalassemia
- Keywords
- Sickle Cell Disease, Beta-Thalassemia, Stem Cell Transplant, Chimerism
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 8 Jul 2026 (actual)
- Primary completion
- 30 Jun 2032 (estimated)
- Study completion
- 30 Jun 2035 (estimated)
- First posted
- 20 May 2026 (actual)
- 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.
This is a non-ablative (partial) stem cell transplant for patients with severe sickle cell disease or beta-thalassemia requiring red cell transfusions. The intensity of the transplant is slightly increased from our previous transplant regimens. The goal is to aim for higher percentage of donor cells to stably remain in the recipients long term.
Detailed description
Study Description:
Our prior non-myeloablative conditioning regimen (03H0170) included 1mg/kg of alemtuzumab divided over 5 days, 300 cGy total body irradiation (TBI), and sirolimus for immune suppression. Sickle disease-free survival (DFS) and overall survival (OS) were 85% and 94% respectively, graft failure 15%, no transplant related mortality (TRM), and acute or chronic GVHD <5%. A large proportion of patients achieved robust (>=95%) donor myeloid chimerism at day 30, but this proportion decreased quickly to 67.2% at 1, 64.9% at 2, and 60% at 3, and 56.9% at 4 years post-transplant.
A subsequent protocol (000539H) added briquilimab, an antibody targeting CD117 (c-Kit), to alem-300 cGy TBI regimen, but did not reduce the gradual decline in donor myeloid chimerism as originally hypothesized, leading to protocol closure. Rates of graft failure was 20%, no TRM, acute GVHD was 5%, and no chronic GVHD. We now propose to increase TBI to 400 cGy to further deplete host lymphoid and myeloid cells to achieve a higher percentage of donor leukocyte engraftment without substantially increasing toxicity. Since we will continue to use filgrastim to mobilize and collect donor hematopoietic cells, we also add abatacept to preserve the low rates of GVHD.
Objectives:
Primary Objective:
To reduce the proportion of patients with graft failure or donor myeloid chimerism <95%
Secondary Objectives:
- To compare CD14/15 and CD3 chimerism to prior MRD HCT protocols (03-H-0170, 14-H-0077, and 000539H)
- To assess the usual transplant related parameters, such as count recovery, transfusion support, rates of GVHD, viral/bacterial infections, rates of transplant related and overall mortality, and compare to prior MRD HCT protocols
Tertiary Objectives:
- To compare changes in organ function
- To examine neuropsychological functioning, wellbeing, and pain before and after HCT
- To obtain reproductive health related changes before and after HCT
Endpoints:
Primary Endpoint: proportion of participants with graft failure or myeloid chimerism <95% at 1 year post HCT
Secondary Endpoints:
- Percent myeloid (CD14/15) chimerism at day 30, 60, 100, 1 year, 2 years, and 3 years post HCT
- Percent T cell (CD3) chimerism at day 30, 60, 100, 1 year, 2 years, and 3 years post HCT
- Day of neutrophil engraftment per CIBMTR definition
- Day of platelet engraftment per CIBMTR definition
- Rates of viral reactivation or infection to day 100 post HCT
- Rates of acute and chronic GVHD at 1 and 2 years post HCT, respectively
- Rates of graft failure or myeloid chimerism <95% at 1 year post HCT
- Transplant related mortality at 1, 2, and 3 years post HCT
- Non-transplant related mortality at 1, 2 and 3 years post HCT
Exploratory Endpoints:
-Quality of life, neuropsychologic function, reproductive health questionnaires, serial testing or imaging of organ function/status
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Matched related donors | Other | Other: Research blood drawDonors for patients |
| Transplant recipients | Experimental | Radiation: Total Body Irradiation, Drug: Alemtuzumab, Drug: Abatacept, Other: Research blood drawPatients with symptomatic sickle cell disease or beta-thalassemia |
Who may qualify
- Ages
- 4 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (31 listed)
- Participants must fulfill one disease category (1 or 2) and 3
- Patients with sickle cell disease at high risk for disease related morbidity or mortality, defined by having an end-organ damage (A, B, C, D, OR E) or complication(s) not ameliorated by sickle cell-specific therapies (F):
- Age (Years): <= 5 / Upper limit of normal serum creatinine (mg/dl): 0.8
- Age (Years): 5 < age <= 10 / Upper limit of normal serum creatinine (mg/dl): 1.0
- Age (Years): 10 < age <= 15 / Upper limit of normal serum creatinine (mg/dl): 1.2
Key exclusion criteria (12 listed)
- Karnofsky or Lanksy performance status of <40
- Diffusing capacity of carbon monoxide <35% predicted: DLCO corrected for hemoglobin or KCO (corrected for lung volume). This criterion may be omitted in young children (e.g. near age 5) or other individuals who may have difficulty understanding or complying with instructions of testing.
- Baseline oxygen saturation of <85% or PaO2 <70
- Left ventricular ejection fraction: <35% estimated by ECHO
- Transaminases >5x upper limit of normal for age
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 |
|---|---|---|
| Total Body IrradiationTotal Body Irradiation 400 cGy | Radiation | Transplant recipients |
| Alemtuzumab1 mg/kg | Drug | Transplant recipients |
| Abatacept10 mg/kg x 6 | Drug | Transplant recipients |
| Research blood drawAbout 5 tablespoons of blood will be collected from donors for research purposes. | Other | Matched related donors, Transplant recipients |
Primary outcome
Donor myeloid chimerism
Time frame: 1 year
percentage of donor myeloid chimerism
3 secondary outcomes
Donor CD3 chimerism
Time frame: 1 year
Overall survival
Time frame: 1 year
Acute Graft versus Host Disease
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No. We are planning to collect and report data as a group.
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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.
John F Tisdale, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Total Body Irradiation, Alemtuzumab and Abatacept in people with Sickle Cell Disease and Beta-thalassemia, run by National Heart, Lung, and Blood Institute (NHLBI) 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 31 inclusion and 12 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: looking for participants now, as of the sponsor's last update on 13 Oct 2026. 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 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.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kelly S Norris, R.N. ((301) 529-7104, kelly.norris@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Donor myeloid chimerism (time frame: 1 year). 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 13 Oct 2026.