Sickle Cell DiseasePhase 1/2NCT06145282
Non-myeloablative Haploidentical HCT Study for Patients With Sickle Cell Disease, Including Compromised Organ Function
A Phase 1/2 study testing Briquilimab, Filgrastim and Abatacept in people with Sickle Cell Disease, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
Background: Sickle cell disease (SCD) is a genetic disorder where red blood cells, that carry oxygen, are stiff and become stuck in small blood vessels. As a result, affected patients can experience severe pain and serious organ damage. Read more about this study
- Who is it for?
- Ages 4 to 100 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Briquilimab, Filgrastim and Abatacept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Dec 2023to 26 Nov 2027
- Phase
- Phase 1/2
- 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 4 to 100 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Recipient:
- Participants must fulfill one disease category, either at least one organ damage or no other access to curative therapy.
- Adult patients with sickle cell disease at high risk for disease-related morbidity or mortality, according to A, B, C, D, or E or complication(s) not ameliorated by SICKLE CELL-SPECIFC THERAPIES (F):
- Stroke defined as a clinically significant neurologic event that is accompanied by an infarct on cerebral MRI OR an abnormal trans-cranial Doppler examination (>=200 m/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
- 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
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- Tricuspid regurgitant jet velocity (TRV) of >=2.5 m/s at least 3 weeks after a vaso-occlusive crisis and/or right heart catheterization-documented pulmonary hypertension; OR
- Sickle hepatopathy defined as EITHER ferritin >1000 mcg/L OR direct bilirubin >0.4 mg/dL at baseline AND a platelet count <250 K/microliter (without vaso-occlusive crisis); OR
- Any one of the below complications:
- Complication: Vaso-occlusive crises; Eligible for HCT: >1 hospital admission per year while on a therapeutic dose of a SCD treatment/medication
- Complication: Acute chest syndrome (ACS); Eligible for HCT: Any ACS while on SCD treatment/medication
- Pediatric patients with sickle cell disease at high risk for disease-related morbidity or mortality, defined as A, B, C, D, E, or F
- A neurological event resulting in focal neurologic deficits that lasted >= 24 hours (classical clinical definition of stroke, not requiring imaging studies of the brain) OR a focal neurological event resulting in abnormalities on T2-weighted or FLAIR images using a MRI scan, indicative of an acute infarct, with no other reasonable medical explanation (definition of a stroke supported with MRI imaging scans of the brain), OR both; OR
- Abnormal transcranial Doppler (TCD) measurement with a timed average maximum mean velocity of at least 200 cm/sec in the terminal portion of the internal carotid or proximal portion of middle cerebral artery or if the imaging TCD method is used > 185 cm/sec plus evidence of intracranial vasculopathy; 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
- Three acute severe vaso-occlusive pain episodes requiring hospitalization and recalcitrant to maximum medical therapy; OR
- At least one acute chest syndrome episode resulting in intensive care admission requiring nonmechanical ventilatory support: simple nasal cannula, face mask that requires oxygen content (venti mask, non-rebreather), simple nasal cannula, face mask oxygen (e.g. ventimask, nonrebreather), continuous positive airway pressure, synchronized inspiratory positive airway pressure, bilevel positive airway pressure, high flow nasal cannula or invasive mechanical ventilatory support (delivered by endotracheal tube or tracheostomy); OR
- Right heart catheterization confirmed pulmonary hypertension defined as pulmonary artery pressure >25 mmHg
- AND evidence of severe organ damage with at least one of the following who are typically excluded from other HCT protocols:
- Kidney damage: CrCl <60 mL/min/1.73m^2 cystatin C-based or iothalamate/iohexol-based or other equivalent GFR testing including patients on hemodialysis or peritoneal dialysis
- Heart damage: Ejection fraction 35-40%
- Liver damage: Bridging fibrosis, cirrhosis, direct bilirubin >= 2x the upper limit of normal and/or ALT >= 5x the upper limit of normal
- Lung damage: Adjusted diffusion capacity of carbon monoxide (DLCO) 35-40% OR who have no other option for curative therapy (including allogeneic HCT, gene therapy, or gene editing studies) on a different SCD HCT protocol.
- Non disease-specific:
- Male or female, age >=18 years (pediatric subjects >=16 years may be enrolled after 6 successful adult transplants)
- Haploidentical relative donor available
- Ability to comprehend and willing to sign an informed consent before the initiation of any study procedures
- Negative serum or urine b-HCG, when applicable
- Agree to use birth control for 12 months after drug product infusion.
- Female subjects must agree to use a medically acceptable method of birth control such as an oral contraceptive, intrauterine device, barrier and spermicide, or contraceptive implant/injection from start of screening through 12 months after drug product infusion.
- Male subjects must agree to use effective contraception (including condoms) from start of screening through 12 months after drug product infusion.
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Donor:
- Haploidentical relative donor deemed suitable and willing to donate, per clinical evaluations. Donors age 4 or older and >=20 kg, eligible to donate hematopoietic stem cells, and who are additionally willing to donate blood for research. Related donors will be evaluated in accordance with existing Standard NIH Policies and Procedures for determination of eligibility and suitability for clinical donation. Note that participation in this study is offered to all related donors, but is not required for a donor to make a stem cell donation, so it is possible that not all related donors will enroll onto this study.
Who cannot join
- Recipient:
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Available HLA-matched sibling donor
- ECOG performance status of 3 or more.
- DLCO <35% predicted (corrected for hemoglobin).
- Baseline oxygen saturation of <85% or PaO2 <70 mmHg
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- Left ventricular ejection fraction: <35% estimated by ECHO
- 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. HCT candidates with pre-transplant respiratory viral infections will undergo careful clinical assessment with the help of our transplant infectious disease team for lower respiratory tract disease, which may include thorough physical examination, imaging, and/or bronchoalveolar lavage. In case of lower respiratory tract disease or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity, the transplant will be delayed until resolution.
- Major anticipated illness or organ failure incompatible with survival from PBSC transplant.
- Pregnant or breastfeeding
- Donor specific anti-HLA antibodies (DSAs) >=2000 Mean Fluorescence Intensity (MFI)
- Patients seronegative for EBV who have EBV seropositive donors
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Non-myeloablative Phase I/II Haploidentical HCT Study for Patients With Sickle Cell Disease, Including Compromised Organ Function
Background:
Sickle cell disease (SCD) is a genetic disorder where red blood cells, that carry oxygen, are stiff and become stuck in small blood vessels. As a result, affected patients can experience severe pain and serious organ damage. SCD can be cured with a hematopoietic cell transplant (HCT), that is, when they receive blood stem cells from a family donor. But HCT can also have serious side effects, especially in people with organ damage. Researchers want to find ways to make HCT safer for everyone.
Read more
Objective:
To test a new combination of drugs (briquilimab, abatacept, and alemtuzumab), used along with radiation, in people undergoing HCT for SCD.
Eligibility:
People aged 16 and older with SCD. They must be eligible for HCT and have a family member who is a good donor match. Donors must be aged 4 and older.
Design:
Participants with SCD will be screened. They will have blood tests and tests of organs including their heart and lung function. Donors will have blood drawn.
Participants with SCD will have a tube inserted into a blood vessel in their chest (intravenously). This line will remain in place up to 2 months; it will be used to draw blood and administer the donor cells and other medications.
Briquilimab will be administered intravenously 1 time, along with other drugs used to prepare for HCT. Participants will receive abatacept 6 times, from just before they receive their donor cells until 6 months after. Participants will undergo radiation therapy and take other drugs that are standard for HCT. Most HCT recipients remain in the hospital for about 30 days after HCT.
Follow-up visits will continue for 5 years....
Read the detailed description
Study Description:
Haploidentical hematopoietic cell transplantation offers a widely available curative option for individuals with sickle cell disease. The goal is to reverse SCD while avoiding unacceptable graft rejection, graft-versus-host disease, infectious complications, and hyperinflammatory responses. We hypothesize that a moderate amount of immunosuppression will maximize efficacy while avoiding unacceptable toxicity.
Objectives:
Primary Objective:
-Evaluate the regimen success rate where success is defined as successful engraftment (persistent donor chimerism and free of acute SCD complications) and absence of acute grade 3 or higher GVHD or moderate to severe chronic GVHD evaluated at 1 year posttransplant.
Secondary Objectives:
- Event-free survival and overall survival.
- Incidence of recipient-type hemoglobin defined as HbS >10% when donors have HbAA and HbS >50% when donors have sickle cell trait (HbAS).
- The proportion of patients with myeloid chimerism >= 95% at 1 and 2 years post-HCT.
- Incidence of acute and chronic GVHD.
- Prevalence of donor type hemoglobin at 1-year post-transplant in SCD patients who have not been transfused in the previous 3 months.
- Incidence of viral reactivation and disease.
- Incidence of autoimmune and hyperinflammatory complications.
- Incidence of hematologic malignancies.
- Transplant-related mortality.
Exploratory Objective:
- Perform gene therapy research involving cell culture or genetic manipulation to produce normal or therapeutic hemoglobin on excess autologous CD34+ cells collected from recipients.
- Evaluate the impact of this non-myeloablative conditioning regimen on organs including the heart, lung, kidneys, liver, brain, neurocognitive function, and endocrine organs
- Evaluate the impact of this non-myeloablative conditioning regimen on quality of life.
Endpoints:
Primary Endpoint:
-The percentage of SCD patients at 1 year (+/- 3 months) posttransplant who have not experienced graft failure and who are without severe graft-versus-host disease (defined as grade 3 and higher acute GVHD and moderate to severe chronic GVHD).
Secondary Endpoints:
- Total hemoglobin and percent HbS levels
- Percent donor myeloid chimerism and donor CD3 chimerism
- Day of neutrophil engraftment
- Day of platelet engraftment
- RBC transfusion requirement
- Rates of acute and chronic GVHD
- Rates of viral reactivation and disease
- Rates of autoimmune and hyperinflammatory complications
- Transplant-related mortality
- Non-transplant-related mortality
- Rates of graft failure
- Rates of leukemia and related disorders
Exploratory Endpoint:
Completion of gene therapy research involving cell culture or genetic manipulation to produce normal or therapeutic hemoglobin on excess autologous CD34+ cells collected from recipients.
Organ function and quality of life
- Conditions
- Sickle Cell Disease
- Being tested
- Briquilimab, Filgrastim, Abatacept, Sirolimus, Cyclophosphamide
- Keywords
- Organ Damage, Hematopoietic Cell Transplant, Haploidentical, Sickle Cell Disease
- 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.
BriquilimabBiological
All stem cell recipient participants will receive the same dose of the investigational briquilimab antibody and abatacept added to the NIH-established regimen of alemtuzumab-TBI-sirolimus and infusion of filgrastim-mobilized peripheral blood hematopoietic cells from haploidentical related donors.
FilgrastimDrug
Also called Granulocyte colony-stimulating factor (G-CSF)
A haploidentical relative donor will receive filgrastim (G-CSF) 10 to 16 µg/kg/d subcutaneously or intravenously for up to 6 days with apheresis collections of peripheral blood hematopoietic progenitor cells (PBPC) after the 5th day (and after the 6th day if required).
AbataceptDrug
All stem cell recipient participants will receive the same dose of the investigational briquilimab antibody and abatacept added to the NIH-established regimen of alemtuzumab-TBI-sirolimus and infusion of filgrastim-mobilized peripheral blood hematopoietic cells from haploidentical related donors.
SirolimusDrug
All stem cell recipient participants will receive the same dose of the investigational briquilimab antibody and abatacept added to the NIH-established regimen of alemtuzumab-TBI-sirolimus and infusion of filgrastim-mobilized peripheral blood hematopoietic cells from haploidentical related donors.
CyclophosphamideDrug
Also called Cy
For cohort 1, stem cell recipient participants will receive a single dose of PT-Cy; 50 mg/kg, on day +3 post-HCT. For cohort 2, stem cell participants will receive two doses of PT-Cy; 50mg/kg, on days +3 and +4 (total 100 mg/kg) post-HCT.
| Study group | Role | What they receive |
|---|---|---|
| PBSC Transplant With 50 mg/kg Post-transplant Cyclophosphamide (PT- Cy) | Experimental | Stem cell recipients with Sickle Cell Disease will receive the same dose of the investigational briquilimab antibody and abatacept added to the NIH-established regimen of alemtuzumab-TBI-sirolimus and infusion of filgrastim-mobilized peripheral blood hematopoietic cells from haploidentical related donors. This group will receive a single dose of PT-Cy; 50 mg/kg, on day +3 post-HCT Receives: Biological: Briquilimab; Drug: Abatacept; Drug: Sirolimus; Drug: Cyclophosphamide |
| PBSC Transplant With 100 mg/kg Post-transplant Cyclophosphamide (PT- Cy) | Experimental | Stem cell recipients with Sickle Cell Disease will receive the same dose of the investigational briquilimab antibody and abatacept added to the NIH-established regimen of alemtuzumab-TBI-sirolimus and infusion of filgrastim-mobilized peripheral blood hematopoietic cells from haploidentical related donors. This group will receive a total of two doses of PT-Cy; 50mg/kg, on days +3 and +4 (total 100 mg/kg) post-HCT Receives: Biological: Briquilimab; Drug: Abatacept; Drug: Sirolimus; Drug: Cyclophosphamide |
| Human Leukocyte Antigens (HLA) Haploidentical Related Stem Cell Donor | Other | A haploidentical relative donor will receive filgrastim (G-CSF) 10 to 16 µg/kg/d subcutaneously or intravenously for up to 6 days with apheresis collections of peripheral blood hematopoietic progenitor cells (PBPC) after the 5th day (and after the 6th day if required). Receives: Drug: Filgrastim |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Successful Engraftment and Absence of Acute Grade 3 or Higher GVHD
Number of participants at 1 year post stem cell transplant who have not experienced graft failure and who are without severe graft-versus-host disease (defined as grade 3 and higher acute GVHD).
Graft failure is defined as the absence of or insufficient donor chimerism associated with the return of acute complications of sickle cell disease.
As defined by CIMBTR criteria for Organ Stages of Acute GVHD:
Grade III: Skin = Rash on >50% of body surface; Liver = Total Bilirubin 6.1 - 15.0 mg/dL; Lower GI = Diarrhea > 1500 mL/day.
Grade IV: Skin = Generalized erythroderma plus bullous formation; Liver = Total Bilirubin >15 mg/dL; Lower GI = Severe abdominal pain with or without ileus.
Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.
Measured: Up to 1 year
Number of Participants With Successful Engraftment and Absence of Moderate to Severe Chronic Graft-versus-host Disease
Number of participants at 1 year post stem cell transplant who have not experienced graft failure and who are without moderate to severe chronic graft-versus-host disease (GVHD)
Graft failure is defined as the absence of or insufficient donor chimerism associated with the return of acute complications of sickle cell disease.
CIMBTR criteria definition for Chronic GVHD: Moderate chronic GVHD involves EITHER 3 organs/sites with no clinically significant functional impairment OR a less than or equal to 1 organ/site with clinically significant functional impairment, but no major disability. Severe GVHD is associated with a major disability caused by chronic GVHD.
Measured: Up to 1 year
Secondary outcomes (3)
Event-free Survival and Overall Survival
Measured: length of study
Viral Reactivation and Disease
Measured: length of study
Autoimmune and Hyperinflammatory Complications
Measured: length of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2023
- Study start28 Dec 2023
- Primary completion27 Oct 2025
- Study completion26 Nov 2027 (estimated)
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 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
- 6 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Courtney F Joseph, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06145282
- Sponsor's protocol ID
- 10001635
- Other IDs
- 001635-H
- Status last verified
- Apr 2026
- First submitted
- 22 Nov 2023
- Last updated
- 29 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-myeloablative Phase I/II Haploidentical HCT Study for Patients With Sickle Cell Disease, Including Compromised Organ Function
- ClinicalTrials.gov ID
- NCT06145282
- Acronym / sponsor ID
- 10001635
- Conditions
- Sickle Cell Disease
- Keywords
- Organ Damage, Hematopoietic Cell Transplant, Haploidentical, Sickle Cell Disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 6 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 28 Dec 2023 (actual)
- Primary completion
- 27 Oct 2025 (actual)
- Study completion
- 26 Nov 2027 (estimated)
- First posted
- 24 Nov 2023 (actual)
- Results
- Posted 29 Apr 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Sickle cell disease (SCD) is a genetic disorder where red blood cells, that carry oxygen, are stiff and become stuck in small blood vessels. As a result, affected patients can experience severe pain and serious organ damage. SCD can be cured with a hematopoietic cell transplant (HCT), that is, when they receive blood stem cells from a family donor. But HCT can also have serious side effects, especially in people with organ damage. Researchers want to find ways to make HCT safer for everyone.
Objective:
To test a new combination of drugs (briquilimab, abatacept, and alemtuzumab), used along with radiation, in people undergoing HCT for SCD.
Eligibility:
People aged 16 and older with SCD. They must be eligible for HCT and have a family member who is a good donor match. Donors must be aged 4 and older.
Design:
Participants with SCD will be screened. They will have blood tests and tests of organs including their heart and lung function. Donors will have blood drawn.
Participants with SCD will have a tube inserted into a blood vessel in their chest (intravenously). This line will remain in place up to 2 months; it will be used to draw blood and administer the donor cells and other medications.
Briquilimab will be administered intravenously 1 time, along with other drugs used to prepare for HCT. Participants will receive abatacept 6 times, from just before they receive their donor cells until 6 months after. Participants will undergo radiation therapy and take other drugs that are standard for HCT. Most HCT recipients remain in the hospital for about 30 days after HCT.
Follow-up visits will continue for 5 years....
Detailed description
Study Description:
Haploidentical hematopoietic cell transplantation offers a widely available curative option for individuals with sickle cell disease. The goal is to reverse SCD while avoiding unacceptable graft rejection, graft-versus-host disease, infectious complications, and hyperinflammatory responses. We hypothesize that a moderate amount of immunosuppression will maximize efficacy while avoiding unacceptable toxicity.
Objectives:
Primary Objective:
-Evaluate the regimen success rate where success is defined as successful engraftment (persistent donor chimerism and free of acute SCD complications) and absence of acute grade 3 or higher GVHD or moderate to severe chronic GVHD evaluated at 1 year posttransplant.
Secondary Objectives:
- Event-free survival and overall survival.
- Incidence of recipient-type hemoglobin defined as HbS >10% when donors have HbAA and HbS >50% when donors have sickle cell trait (HbAS).
- The proportion of patients with myeloid chimerism >= 95% at 1 and 2 years post-HCT.
- Incidence of acute and chronic GVHD.
- Prevalence of donor type hemoglobin at 1-year post-transplant in SCD patients who have not been transfused in the previous 3 months.
- Incidence of viral reactivation and disease.
- Incidence of autoimmune and hyperinflammatory complications.
- Incidence of hematologic malignancies.
- Transplant-related mortality.
Exploratory Objective:
- Perform gene therapy research involving cell culture or genetic manipulation to produce normal or therapeutic hemoglobin on excess autologous CD34+ cells collected from recipients.
- Evaluate the impact of this non-myeloablative conditioning regimen on organs including the heart, lung, kidneys, liver, brain, neurocognitive function, and endocrine organs
- Evaluate the impact of this non-myeloablative conditioning regimen on quality of life.
Endpoints:
Primary Endpoint:
-The percentage of SCD patients at 1 year (+/- 3 months) posttransplant who have not experienced graft failure and who are without severe graft-versus-host disease (defined as grade 3 and higher acute GVHD and moderate to severe chronic GVHD).
Secondary Endpoints:
- Total hemoglobin and percent HbS levels
- Percent donor myeloid chimerism and donor CD3 chimerism
- Day of neutrophil engraftment
- Day of platelet engraftment
- RBC transfusion requirement
- Rates of acute and chronic GVHD
- Rates of viral reactivation and disease
- Rates of autoimmune and hyperinflammatory complications
- Transplant-related mortality
- Non-transplant-related mortality
- Rates of graft failure
- Rates of leukemia and related disorders
Exploratory Endpoint:
Completion of gene therapy research involving cell culture or genetic manipulation to produce normal or therapeutic hemoglobin on excess autologous CD34+ cells collected from recipients.
Organ function and quality of life
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| PBSC Transplant With 50 mg/kg Post-transplant Cyclophosphamide (PT- Cy) | Experimental | Biological: Briquilimab, Drug: Abatacept, Drug: Sirolimus, Drug: CyclophosphamideStem cell recipients with Sickle Cell Disease will receive the same dose of the investigational briquilimab antibody and abatacept added to the NIH-established regimen of alemtuzumab-TBI-sirolimus and infusion of filgrastim-mobilized peripheral blood hematopoietic cells from haploidentical related donors. This group will receive a single dose of PT-Cy; 50 mg/kg, on day +3 post-HCT |
| PBSC Transplant With 100 mg/kg Post-transplant Cyclophosphamide (PT- Cy) | Experimental | Biological: Briquilimab, Drug: Abatacept, Drug: Sirolimus, Drug: CyclophosphamideStem cell recipients with Sickle Cell Disease will receive the same dose of the investigational briquilimab antibody and abatacept added to the NIH-established regimen of alemtuzumab-TBI-sirolimus and infusion of filgrastim-mobilized peripheral blood hematopoietic cells from haploidentical related donors. This group will receive a total of two doses of PT-Cy; 50mg/kg, on days +3 and +4 (total 100 mg/kg) post-HCT |
| Human Leukocyte Antigens (HLA) Haploidentical Related Stem Cell Donor | Other | Drug: FilgrastimA haploidentical relative donor will receive filgrastim (G-CSF) 10 to 16 µg/kg/d subcutaneously or intravenously for up to 6 days with apheresis collections of peripheral blood hematopoietic progenitor cells (PBPC) after the 5th day (and after the 6th day if required). |
Who may qualify
- Ages
- 4 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (34 listed)
- Participants must fulfill one disease category, either at least one organ damage or no other access to curative therapy.
- Adult patients with sickle cell disease at high risk for disease-related morbidity or mortality, according to A, B, C, D, or E or complication(s) not ameliorated by SICKLE CELL-SPECIFC THERAPIES (F):
- Complication: Vaso-occlusive crises; Eligible for HCT: >1 hospital admission per year while on a therapeutic dose of a SCD treatment/medication
- Complication: Acute chest syndrome (ACS); Eligible for HCT: Any ACS while on SCD treatment/medication
- Pediatric patients with sickle cell disease at high risk for disease-related morbidity or mortality, defined as A, B, C, D, E, or F
Key exclusion criteria (12 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Available HLA-matched sibling donor
- ECOG performance status of 3 or more.
- DLCO <35% predicted (corrected for hemoglobin).
- Baseline oxygen saturation of <85% or PaO2 <70 mmHg
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 |
|---|---|---|
| BriquilimabAll stem cell recipient participants will receive the same dose of the investigational briquilimab antibody and abatacept added to the NIH-established regimen of alemtuzumab-TBI-sirolimus and infusion of filgrastim-mobilized peripheral blood hematopoietic cells from haploidentical related donors. | Biological | PBSC Transplant With 100 mg/kg Post-transplant Cyclophosphamide (PT- Cy), PBSC Transplant With 50 mg/kg Post-transplant Cyclophosphamide (PT- Cy) |
| FilgrastimAlso: Granulocyte colony-stimulating factor (G-CSF)A haploidentical relative donor will receive filgrastim (G-CSF) 10 to 16 µg/kg/d subcutaneously or intravenously for up to 6 days with apheresis collections of peripheral blood hematopoietic progenitor cells (PBPC) after the 5th day (and after the 6th day if required). | Drug | Human Leukocyte Antigens (HLA) Haploidentical Related Stem Cell Donor |
| AbataceptAll stem cell recipient participants will receive the same dose of the investigational briquilimab antibody and abatacept added to the NIH-established regimen of alemtuzumab-TBI-sirolimus and infusion of filgrastim-mobilized peripheral blood hematopoietic cells from haploidentical related donors. | Drug | PBSC Transplant With 100 mg/kg Post-transplant Cyclophosphamide (PT- Cy), PBSC Transplant With 50 mg/kg Post-transplant Cyclophosphamide (PT- Cy) |
| SirolimusAll stem cell recipient participants will receive the same dose of the investigational briquilimab antibody and abatacept added to the NIH-established regimen of alemtuzumab-TBI-sirolimus and infusion of filgrastim-mobilized peripheral blood hematopoietic cells from haploidentical related donors. | Drug | PBSC Transplant With 100 mg/kg Post-transplant Cyclophosphamide (PT- Cy), PBSC Transplant With 50 mg/kg Post-transplant Cyclophosphamide (PT- Cy) |
| CyclophosphamideAlso: CyFor cohort 1, stem cell recipient participants will receive a single dose of PT-Cy; 50 mg/kg, on day +3 post-HCT. For cohort 2, stem cell participants will receive two doses of PT-Cy; 50mg/kg, on days +3 and +4 (total 100 mg/kg) post-HCT. | Drug | PBSC Transplant With 100 mg/kg Post-transplant Cyclophosphamide (PT- Cy), PBSC Transplant With 50 mg/kg Post-transplant Cyclophosphamide (PT- Cy) |
Primary outcome
Number of Participants With Successful Engraftment and Absence of Acute Grade 3 or Higher GVHD
Time frame: Up to 1 year
Number of participants at 1 year post stem cell transplant who have not experienced graft failure and who are without severe graft-versus-host disease (defined as grade 3 and higher acute GVHD). Graft failure is defined as the absence of or insufficient donor chimerism associated with the return of acute complications of sickle cell disease. As defined by CIMBTR criteria for Organ Stages of Acute GVHD: Grade III: Skin = Rash on >50% of body surface; Liver = Total Bilirubin 6.1 - 15.0 mg/dL; Lower GI = Diarrhea > 1500 mL/day. Grade IV: Skin = Generalized erythroderma plus bullous formation; Liver = Total Bilirubin >15 mg/dL; Lower GI = Severe abdominal pain with or without ileus. Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.
Number of Participants With Successful Engraftment and Absence of Moderate to Severe Chronic Graft-versus-host Disease
Time frame: Up to 1 year
Number of participants at 1 year post stem cell transplant who have not experienced graft failure and who are without moderate to severe chronic graft-versus-host disease (GVHD) Graft failure is defined as the absence of or insufficient donor chimerism associated with the return of acute complications of sickle cell disease. CIMBTR criteria definition for Chronic GVHD: Moderate chronic GVHD involves EITHER 3 organs/sites with no clinically significant functional impairment OR a less than or equal to 1 organ/site with clinically significant functional impairment, but no major disability. Severe GVHD is associated with a major disability caused by chronic GVHD.
3 secondary outcomes
Event-free Survival and Overall Survival
Time frame: length of study
Viral Reactivation and Disease
Time frame: length of study
Autoimmune and Hyperinflammatory Complications
Time frame: length of study
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Courtney F Joseph, 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 Briquilimab, Filgrastim and Abatacept in people with Sickle Cell Disease, 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 34 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: under way, not looking for participants, as of the sponsor's last update on 29 Apr 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?
Yes. Results are posted in the registry (first posted 29 Apr 2026). 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?
Number of Participants With Successful Engraftment and Absence of Acute Grade 3 or Higher GVHD (time frame: Up to 1 year). The study lists 2 primary outcomes in all. 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 29 Apr 2026.