Sickle Cell DiseasePhase 1/2NCT03077542
Nonmyeloablative Haploidentical Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Sickle Cell Disease
A Phase 1/2 study testing haploidentical stem cell transplant, Sirolimus and Alemtuzumab in people with Sickle Cell Disease, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
Background: Peripheral blood stem cell transplantation procedures are used for people with sickle cell disease. Researchers want to improve the success and reduce the complications for these procedures. This might allow more people to have a transplant. Read more about this study
- Who is it for?
- Ages 2 to 100 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- haploidentical stem cell transplant, Sirolimus and Alemtuzumab
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Apr 2017to 31 Aug 2026
- 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 2 to 100 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with any type of sickle cell disease who are at high risk for disease-related cerebrovascular morbidity or early mortality, defined by having severe end-organ damage (A, B, C, D, or E):
- A neurologic 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 an 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
- Tricuspid regurgitant jet velocity (TRV) of >= 2.7 m/s at baseline (without vaso- occlusive crisis) and/or pulmonary hypertension; OR
- Sickle hepatopathy defined as either ferritin >1000 mcg/L and platelet count < 250,000/uL (without vaso-occlusive crisis) OR direct bilirubin > 0.4 mg/dL and platelet count <250,000/uL (without vaso- occlusive crisis)
- Any acute chest syndrome episode resulting in intensive care admission requiring non- mechanical ventilatory support: simple nasal cannula, face mask that requires oxygen content (venti mask, non-rebreather), continuous positive airway pressure (CPAP), Bilevel positive airway pressure (BiPAP), high flow nasal cannula (HFNC) or invasive mechanical ventilatory support (delivered by endotracheal tube or tracheostomy).
- 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 or an abnormality on examination that could not be explained by the location of the brain lesion(s).
Show all 24Show fewer
- Non-disease specific:
- Age greater than or equal to 18 years
- Haploidentical relative donor available
- Ability to comprehend and willing to sign an informed consent
- Negative serum beta-HCG
- Ejection fraction greater than or equal to 35%
- Glomerular filtration rate >60 mL/min/1.73m^2 by cystatin C-based or iothalamate-based or other equivalent GFR testing
- Adjusted DLCO greater than or equal to 35%
- EXCLUSION CRITERIA RECIPIENT: (any of the following would exclude the subject from participating)
- Available 6/6 HLA-matched sibling donor
- ECOG performance status of 3 or more (See Appendix A)
- 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.
- Patients with fever or suspected minor infection should await resolution of symptoms before starting the conditioning regimen.
- Major anticipated illness or organ failure incompatible with survival from PBSC transplant
- Pregnant or breast-feeding
- Donor specific anti-HLA antibodies (DSAs) greater than or equal to 2000 Mean Fluorescence Intensity (MFI)
- Patients seronegative for EBV who have EBV seropositive donors
- Haploidentical relative donor deemed suitable and eligible, and willing to donate, per clinical evaluations 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 do le that not all related donors will enroll onto this study.
Who cannot join
- None
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Background:
Peripheral blood stem cell transplantation procedures are used for people with sickle cell disease. Researchers want to improve the success and reduce the complications for these procedures. This might allow more people to have a transplant.
Read more
Objective:
To see if a new transplant regime is effective, safe and well tolerated in people with sickle cell disease.
Eligibility:
Adults at least 18 years old with sickle cell disease and certain complications.
A relative who is a half tissue match.
Design:
Participants will be screened with medical history, physical exam, and blood tests. Recipients will also have:
- Heart, lung, and mental health tests
- Chest x-rays
- Bone marrow taken from the pelvic bone
- Eyes and teeth checked
Recipients will have a large central line inserted into a vein for up to 6 months.
Donors will have their veins tested and have an IV inserted for 1 day or on rare occasions 2 days.
Donors will get a drug to activate bone marrow. It will be injected for about 6 days.
Donors will have at least 1 five-hour procedure where bone marrow stem cells will be collected. Blood will be taken from a vein in one arm or in rare cases from a groin vein and put through a machine. Some blood will be saved and the rest will be returned. Stem cells will be taken from the saved blood in a lab and frozen until ready to give to the recipient.
Recipients will have:
- Stems cells collected and frozen
- Hygiene lessons
- Bone density scans
- Low-dose radiation
- Drugs for their immune system
- Donor cells infused through their central line
- Transfusions
After about 30 days, recipients will leave the hospital. They must stay near NIH for 3 months after the transplant and have frequent visits. After returning home, they will have 8 visits over 5 years, then be contacted yearly.
Read the detailed description
Nonmyeloablative allogeneic peripheral blood stem cell (PBSC) transplants are currently being investigated in phase I/II trials assessing engraftment, efficacy, and toxicity at a number of transplant centers. Our ongoing protocol for patients with severe congenital anemias, particularly sickle cell disease (SCD), and an HLA-matched sibling donor has had excellent preliminary results. None of the patients who engrafted had sickle-related events or any evidence of graft versus host disease (GVHD). There was no significant toxicity associated with the conditioning regimen. An additional protocol is ongoing for patients with high risk of graft rejection which employs pentostatin and oral cyclophosphamide (PC) pre-transplant to further deplete recipient lymphocytes in an attempt to decrease the rate of graft rejection. Four of 4 patients transplanted remain free of SCD.
Our main limitation has been a lack of HLA-matched sibling donors in the majority of patients. We performed a study in which patients with severe SCD who lacked a suitable donor underwent a search for a matched unrelated donor or umbilical cord donor. The vast majority of patients were not found to have an appropriate alternative donor. We therefore seek to develop a safe nonmyeloablative regimen to be applied to the haploidentical setting so that family members can serve as donors and greatly expand the donor pool.
We developed a nonmyeloablative haploidentical PBSC transplant protocol which included 3 cohorts, with stopping rules built in for regimen failure, defined as graft rejection or severe GVHD. All included 400 cGy total body irradiation (TBI) in divided doses 1 and 2 days prior to transplant, alemtuzumab, and sirolimus. The first cohort included no cyclophosphamide. The 2nd included one dose of cyclophosphamide given at 50mg/kg on day 3 post-transplant, and the 3rd included 100mg/kg cyclophosphamide given in divided doses on days 3 and 4 post-transplant. The engraftment rate and percentage of patients who remained free of SCD improved with each successive cohort. However, the graft rejection rate in the 3rd cohort remained high at 50%. To attempt to reduce the rate of graft rejection in the haploidentical setting, this protocol will add PC to the conditioning regimen.
In this protocol, we propose PBSC transplantation in patients with SCD considered at high risk for complications from or ineligible for standard bone marrow transplantation, with allogeneic peripheral blood stem cells from a haploidentical donor using a novel immunosuppressive regimen without myeloablation in an attempt to further decrease the transplant-related morbidity/mortality. The low intensity nonmyeloablative conditioning regimen will consist of a relatively low radiation dose for therapeutic radiation, Alemtuzumab (Campath ), Sirolimus (Rapamune ), Cyclophosphamide (Cytoxan ), and pentostatin (Nipent ) as a strategy to provide adequate immunosuppression to allow sufficient engraftment for clinical remission with a lower risk of GVHD development. T-cell replete, donor-derived, granulocyte colony-stimulating factor (G-CSF)- mobilized PBSC will be used to establish hematopoietic and lymphoid reconstitution.
The primary endpoint of this study is the percentage of patients at 100 days post-transplant who have not rejected their grafts, and who are without severe GVHD (defined as grade 3 and higher acute GVHD and moderate to severe chronic GVHD). Other endpoints include degree of donor-host chimerism necessary for long-term graft survival and disease amelioration, incidence of acute and chronic GVHD, incidence of graft rejection, transplant-related morbidity, as well as disease-free and overall survival.
- Conditions
- Sickle Cell Disease
- Being tested
- haploidentical stem cell transplant, Sirolimus, Alemtuzumab, Pentostatin, Cyclophosphamide
- Keywords
- Peripheral Blood Stem Cells, Host-Donor Chimerism, Graft-Versus-Host Disease, Haploidentical, Donor Apheresis
- Medical subject headings
- Anemia, Sickle Cell, Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
haploidentical stem cell transplantProcedure or surgery
haploidentical stem cell transplant
SirolimusDrug
Also called Rapamune
conditioning regimen
AlemtuzumabDrug
Also called Campth
conditioning regimen
PentostatinDrug
Also called Nipent
conditioning regimen
CyclophosphamideDrug
Also called Cytoxan
conditioning regimen
HydroxyureaDrug
Also called HU, Hydrea, Droxia
conditioning regimen
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).
| Study group | Role | What they receive |
|---|---|---|
| Participants with Sickle Cell Disease with Nonmyeloablative Haplo Transplants | Experimental | Participants will receive pentostatin on days -21, -17, -13, and -9 and oral cyclophosphamide from days -21 to -8. Alemtuzumab to be infused on days -7 to -3, followed by 400 cGy TBI on day -1. Donor-derived peripheral blood stem cells will be given on Day 0 then cyclophosphamide will be given at 50 mg/kg on day +3. Sirolimus loading dose of 5mg PO q4h x three doses at one day after the completion of cyclophosphamide (on day +4) and continued the following day at 5mg PO q24h to maintain trough levels between 5-15 ng/ml. Receives: Procedure: haploidentical stem cell transplant; Drug: Sirolimus; Drug: Alemtuzumab; Drug: Pentostatin; Drug: Cyclophosphamide; Drug: Hydroxyurea |
| 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.
Percentage of Participants Who Have Not Rejected Their Stem Cell Graft and Who Are Without Severe Graft-versus-host Disease Following Stem Cell Transplant
The percentage of sickle cell participants at 100 days post-transplant who have not rejected their grafts and who are without severe graft-versus-host disease (GVHD). Severe GVHD is defined as grade 3 or higher for acute GVHD and moderate to severe for chronic GVHD according to NIH Consensus Criteria.
Stem cell graft rejection is defined as
Measured: 100 days post transplant
Secondary outcomes (10)
Chimeric Value That is Required to Maintain Graft Survival and Hematologic Normalcy.
The level of chimerism required to maintain both graft survival as well as hematologic normalcy. Hematologic normalcy may be defined as: being free from acute complications of sickle cell disease.
The chimeric status of patients will be measured on days +14 (or when subject starts to engraft), +30, +60 and +100, and periodically after day +100, by microsatellite analysis of the peripheral blood.
Engraftment of donor cells was assessed with the use of methods that detect informative polymorphisms in regions known to contain short tandem repeats. Peripheral-blood CD3+ T cells and CD14+CD15+ myeloid cells were selected for analysis with the use of immunomagnetic beads (Dynal).
Measured: Up to Year 5
Incidence of Donor Type Hemoglobin Post-transplant in SCD Patients Who Have Not Been Transfused in the Previous 3 Months.
Incidence of donor type hemoglobin at 1 year post-transplant in SCD patients who have not been transfused in the previous 3 months.
Measured: 1 year
Number of Participants Who Developed Acute GVHD Grades I, II, III, IV
Number of participants who developed Acute Graft vs Host Disease (GVHD) Grades I, II, III, IV as defined by CIMBTR criteria for Organ Stages of Acute GVHD.
Grades are defined as:
Grade I: Skin = Maculopapular rash< 25% of body surface area (BSA); Liver = Total Bilirubin 2-3 mg/dL; Lower GI = stool output/day is 500-999 mL/day.
Grade II: Skin = rash on 25-50 percent body surface area; Liver = Total Bilirubin 3.1-6.0 mg/dL; Lower GI = Diarrhea 1001-1500 mL/day.
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: Day 100
Number of Participants Who Developed Moderate or Severe Chronic Graft vs Host Disease (GVHD)
Number of Participants Who Developed Moderate or Severe Chronic Graft vs Host Disease (GVHD) up to 5 years.
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 Year 5
Number of Participant That Are Disease-free Survival Following Stem Cell Transplant
Number of participant that are disease-free survival following stem cell transplant. Disease-free survival is defined as alive and free of acute complications related to sickle cell disease.
Measured: Up to Year 5
Number of Participant Overall Survival Following Stem Cell Transplant
Number of Participant Overall Survival up to year 5 following stem cell transplant. Overall survival is defined as being alive following stem cell transplant.
Measured: Up to Year 5
Incidence of Graft Failure Following Stem Cell Transplant
Incidence of graft failure following stem cell transplant. Graft failure is defined as the absence of or insufficient donor chimerism associated with the return of acute complications of sickle cell disease.
Measured: Up to 5 Years
Participant Graft Rejection Rate Following Stem Cell Transplant
Participant graft rejection rate following stem cell transplant. Graft rejection is defined as donor myeloid chimerism and donor lymphoid chimerism <5%.
Measured: Up to 5 years
Number of Participants That Experienced Transplant-related Mortality
Number of participants that experienced transplant-related mortality. Transplant-related mortality is defined as death that is at least possibly related to the transplant (GVHD, toxicity, infection, other causes).
Measured: 1 year
Number of Participants That Experienced Regimen Failure by Type of Haploidentical Donor
Determine whether the type of haploidentical donor impacts the incidence of regimen failure. Number of participants that experienced regimen failure and type of haploidentical donor. Determine whether specific haploidentical donors (i.e. parent versus sibling versus child) will decrease the incidence of regimen failure. Haploidentical donor analyses include mother versus father, parent versus sibling, and parent versus child.
Measured: Up to Year 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2017
- Study start6 Apr 2017
- Primary completion27 Jul 2023
- Study completion31 Aug 2026 (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.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by 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
- Single group
- Masking
- None (open label)
- Enrolment
- 57 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
- NCT03077542
- Sponsor's protocol ID
- 170069
- Other IDs
- 17-H-0069
- Status last verified
- Apr 2026
- First submitted
- 10 Mar 2017
- Last updated
- 23 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Kern KC, Inam Z, Hsieh MM, Tisdale JF, Fitzhugh CD, Limerick EM, Gebremeskel ASK, White T, Jordan LC, Lynch JK. Hematopoietic Stem Cell Transplant and Brain Volume Changes in Adults With Sickle Cell Disease. Neurology. 2026 Jun 9;106(11):e218050. doi: 10.1212/WNL.0000000000218050. Epub 2026 May 14.
PubMed 42133908Limerick E, Hsieh M, Queen J, Grecco ML, Varga J, Brooks J, Coles W, Jeffries N, Fitzhugh CD. Nonmyeloablative pentostatin-cyclophosphamide preconditioning improves rates of engraftment in adults undergoing haploidentical HCT for sickle cell disease. PLoS One. 2026 Mar 23;21(3):e0332282. doi: 10.1371/journal.pone.0332282. eCollection 2026.
PubMed 41871072Leonard 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 23 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nonmyeloablative Haploidentical Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT03077542
- Acronym / sponsor ID
- 170069
- Conditions
- Sickle Cell Disease
- Keywords
- Peripheral Blood Stem Cells, Host-Donor Chimerism, Graft-Versus-Host Disease, Haploidentical, Donor Apheresis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 57 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 6 Apr 2017 (actual)
- Primary completion
- 27 Jul 2023 (actual)
- Study completion
- 31 Aug 2026 (estimated)
- First posted
- 13 Mar 2017 (actual)
- Results
- Posted 7 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Peripheral blood stem cell transplantation procedures are used for people with sickle cell disease. Researchers want to improve the success and reduce the complications for these procedures. This might allow more people to have a transplant.
Objective:
To see if a new transplant regime is effective, safe and well tolerated in people with sickle cell disease.
Eligibility:
Adults at least 18 years old with sickle cell disease and certain complications.
A relative who is a half tissue match.
Design:
Participants will be screened with medical history, physical exam, and blood tests. Recipients will also have:
- Heart, lung, and mental health tests
- Chest x-rays
- Bone marrow taken from the pelvic bone
- Eyes and teeth checked
Recipients will have a large central line inserted into a vein for up to 6 months.
Donors will have their veins tested and have an IV inserted for 1 day or on rare occasions 2 days.
Donors will get a drug to activate bone marrow. It will be injected for about 6 days.
Donors will have at least 1 five-hour procedure where bone marrow stem cells will be collected. Blood will be taken from a vein in one arm or in rare cases from a groin vein and put through a machine. Some blood will be saved and the rest will be returned. Stem cells will be taken from the saved blood in a lab and frozen until ready to give to the recipient.
Recipients will have:
- Stems cells collected and frozen
- Hygiene lessons
- Bone density scans
- Low-dose radiation
- Drugs for their immune system
- Donor cells infused through their central line
- Transfusions
After about 30 days, recipients will leave the hospital. They must stay near NIH for 3 months after the transplant and have frequent visits. After returning home, they will have 8 visits over 5 years, then be contacted yearly.
Detailed description
Nonmyeloablative allogeneic peripheral blood stem cell (PBSC) transplants are currently being investigated in phase I/II trials assessing engraftment, efficacy, and toxicity at a number of transplant centers. Our ongoing protocol for patients with severe congenital anemias, particularly sickle cell disease (SCD), and an HLA-matched sibling donor has had excellent preliminary results. None of the patients who engrafted had sickle-related events or any evidence of graft versus host disease (GVHD). There was no significant toxicity associated with the conditioning regimen. An additional protocol is ongoing for patients with high risk of graft rejection which employs pentostatin and oral cyclophosphamide (PC) pre-transplant to further deplete recipient lymphocytes in an attempt to decrease the rate of graft rejection. Four of 4 patients transplanted remain free of SCD.
Our main limitation has been a lack of HLA-matched sibling donors in the majority of patients. We performed a study in which patients with severe SCD who lacked a suitable donor underwent a search for a matched unrelated donor or umbilical cord donor. The vast majority of patients were not found to have an appropriate alternative donor. We therefore seek to develop a safe nonmyeloablative regimen to be applied to the haploidentical setting so that family members can serve as donors and greatly expand the donor pool.
We developed a nonmyeloablative haploidentical PBSC transplant protocol which included 3 cohorts, with stopping rules built in for regimen failure, defined as graft rejection or severe GVHD. All included 400 cGy total body irradiation (TBI) in divided doses 1 and 2 days prior to transplant, alemtuzumab, and sirolimus. The first cohort included no cyclophosphamide. The 2nd included one dose of cyclophosphamide given at 50mg/kg on day 3 post-transplant, and the 3rd included 100mg/kg cyclophosphamide given in divided doses on days 3 and 4 post-transplant. The engraftment rate and percentage of patients who remained free of SCD improved with each successive cohort. However, the graft rejection rate in the 3rd cohort remained high at 50%. To attempt to reduce the rate of graft rejection in the haploidentical setting, this protocol will add PC to the conditioning regimen.
In this protocol, we propose PBSC transplantation in patients with SCD considered at high risk for complications from or ineligible for standard bone marrow transplantation, with allogeneic peripheral blood stem cells from a haploidentical donor using a novel immunosuppressive regimen without myeloablation in an attempt to further decrease the transplant-related morbidity/mortality. The low intensity nonmyeloablative conditioning regimen will consist of a relatively low radiation dose for therapeutic radiation, Alemtuzumab (Campath ), Sirolimus (Rapamune ), Cyclophosphamide (Cytoxan ), and pentostatin (Nipent ) as a strategy to provide adequate immunosuppression to allow sufficient engraftment for clinical remission with a lower risk of GVHD development. T-cell replete, donor-derived, granulocyte colony-stimulating factor (G-CSF)- mobilized PBSC will be used to establish hematopoietic and lymphoid reconstitution.
The primary endpoint of this study is the percentage of patients at 100 days post-transplant who have not rejected their grafts, and who are without severe GVHD (defined as grade 3 and higher acute GVHD and moderate to severe chronic GVHD). Other endpoints include degree of donor-host chimerism necessary for long-term graft survival and disease amelioration, incidence of acute and chronic GVHD, incidence of graft rejection, transplant-related morbidity, as well as disease-free and overall survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Participants with Sickle Cell Disease with Nonmyeloablative Haplo Transplants | Experimental | Procedure: haploidentical stem cell transplant, Drug: Sirolimus, Drug: Alemtuzumab, Drug: Pentostatin, Drug: Cyclophosphamide, Drug: HydroxyureaParticipants will receive pentostatin on days -21, -17, -13, and -9 and oral cyclophosphamide from days -21 to -8. Alemtuzumab to be infused on days -7 to -3, followed by 400 cGy TBI on day -1. Donor-derived peripheral blood stem cells will be given on Day 0 then cyclophosphamide will be given at 50 mg/kg on day +3. Sirolimus loading dose of 5mg PO q4h x three doses at one day after the completion of cyclophosphamide (on day +4) and continued the following day at 5mg PO q24h to maintain trough levels between 5-15 ng/ml. |
| 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
- 2 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (24 listed)
- Patients with any type of sickle cell disease who are at high risk for disease-related cerebrovascular morbidity or early mortality, defined by having severe end-organ damage (A, B, C, D, or E):
- A neurologic 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 an 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
- Tricuspid regurgitant jet velocity (TRV) of >= 2.7 m/s at baseline (without vaso- occlusive crisis) and/or pulmonary hypertension; OR
- Sickle hepatopathy defined as either ferritin >1000 mcg/L and platelet count < 250,000/uL (without vaso-occlusive crisis) OR direct bilirubin > 0.4 mg/dL and platelet count <250,000/uL (without vaso- occlusive crisis)
- Any acute chest syndrome episode resulting in intensive care admission requiring non- mechanical ventilatory support: simple nasal cannula, face mask that requires oxygen content (venti mask, non-rebreather), continuous positive airway pressure (CPAP), Bilevel positive airway pressure (BiPAP), high flow nasal cannula (HFNC) or invasive mechanical ventilatory support (delivered by endotracheal tube or tracheostomy).
Key exclusion criteria (1 listed)
- None
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 |
|---|---|---|
| haploidentical stem cell transplanthaploidentical stem cell transplant | Procedure or surgery | Participants with Sickle Cell Disease with Nonmyeloablative Haplo Transplants |
| SirolimusAlso: Rapamuneconditioning regimen | Drug | Participants with Sickle Cell Disease with Nonmyeloablative Haplo Transplants |
| AlemtuzumabAlso: Campthconditioning regimen | Drug | Participants with Sickle Cell Disease with Nonmyeloablative Haplo Transplants |
| PentostatinAlso: Nipentconditioning regimen | Drug | Participants with Sickle Cell Disease with Nonmyeloablative Haplo Transplants |
| CyclophosphamideAlso: Cytoxanconditioning regimen | Drug | Participants with Sickle Cell Disease with Nonmyeloablative Haplo Transplants |
| HydroxyureaAlso: HU, Hydrea, Droxiaconditioning regimen | Drug | Participants with Sickle Cell Disease with Nonmyeloablative Haplo Transplants |
| 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 |
Primary outcome
Percentage of Participants Who Have Not Rejected Their Stem Cell Graft and Who Are Without Severe Graft-versus-host Disease Following Stem Cell Transplant
Time frame: 100 days post transplant
The percentage of sickle cell participants at 100 days post-transplant who have not rejected their grafts and who are without severe graft-versus-host disease (GVHD). Severe GVHD is defined as grade 3 or higher for acute GVHD and moderate to severe for chronic GVHD according to NIH Consensus Criteria. Stem cell graft rejection is defined as
10 secondary outcomes
Chimeric Value That is Required to Maintain Graft Survival and Hematologic Normalcy.
Time frame: Up to Year 5
Incidence of Donor Type Hemoglobin Post-transplant in SCD Patients Who Have Not Been Transfused in the Previous 3 Months.
Time frame: 1 year
Number of Participants Who Developed Acute GVHD Grades I, II, III, IV
Time frame: Day 100
Number of Participants Who Developed Moderate or Severe Chronic Graft vs Host Disease (GVHD)
Time frame: Up to Year 5
Number of Participant That Are Disease-free Survival Following Stem Cell Transplant
Time frame: Up to Year 5
Number of Participant Overall Survival Following Stem Cell Transplant
Time frame: Up to Year 5
Incidence of Graft Failure Following Stem Cell Transplant
Time frame: Up to 5 Years
Participant Graft Rejection Rate Following Stem Cell Transplant
Time frame: Up to 5 years
Number of Participants That Experienced Transplant-related Mortality
Time frame: 1 year
Number of Participants That Experienced Regimen Failure by Type of Haploidentical Donor
Time frame: Up to Year 5
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42133908Kern KC, Inam Z, Hsieh MM, Tisdale JF, Fitzhugh CD, Limerick EM, Gebremeskel ASK, White T, Jordan LC, Lynch JK. Hematopoietic Stem Cell Transplant and Brain Volume Changes in Adults With Sickle Cell Disease. Neurology. 2026 Jun 9;106(11):e218050. doi: 10.1212/WNL.0000000000218050. Epub 2026 May 14.
- Derived from this study: PubMed 41871072Limerick E, Hsieh M, Queen J, Grecco ML, Varga J, Brooks J, Coles W, Jeffries N, Fitzhugh CD. Nonmyeloablative pentostatin-cyclophosphamide preconditioning improves rates of engraftment in adults undergoing haploidentical HCT for sickle cell disease. PLoS One. 2026 Mar 23;21(3):e0332282. doi: 10.1371/journal.pone.0332282. eCollection 2026.
- 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
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 haploidentical stem cell transplant, Sirolimus and Alemtuzumab 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 24 inclusion and 1 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 23 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 7 Aug 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?
Percentage of Participants Who Have Not Rejected Their Stem Cell Graft and Who Are Without Severe Graft-versus-host Disease Following Stem Cell Transplant (time frame: 100 days post transplant). 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 NCT03077542, which also lists 3 linked publications.
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 23 Apr 2026.