A Phase 2 interventional study of hydroxyurea, azathioprine, alemtuzumab, thioptepa, low dose total body irradiation and sirolimus and hydroxyurea, azathioprine, alemtuzumab, thiotepa, plerixafor, low dose total body irradiation, cyclophosphamide and sirolimus in Sickle Cell Disease, sponsored by St. Jude Children's Research Hospital. Active, not recruiting at 1 site in United States. Open to participants aged 2 Years to 25 Years. Per ClinicalTrials.gov, last updated 2026-09-01.
Sponsored by St. Jude Children's Research Hospital · Phase 2, Interventional, and Treatment
This study is being done to test a transplant method that may have fewer side effects (or less toxic, less harmful) than conventional high dose chemotherapy conditioning-based transplants for children and young adults with Sickle Cell Disease (SCD). Patients less than or equal to 25 years old with SCD who would likely benefit from allogeneic hematopoietic cell transplantation (HCT) will be included in this study. Patients with a suitable HLA matched sibling donor (MSD) will be enrolled on the MSD arm while patients without an eligible MSD who have a suitable haploidentical (HAPLO) donor available will be enrolled on the HAPLO arm of the study.
Primary Objective
To assess the donor T-cell chimerism at 1-year post transplant in each respective arm (MSD, HAPLO) of the trial.
Secondary Objectives
Exploratory Objectives
This is a prospective single center phase II study of a reduced intensity conditioning based hematopoietic cell transplant for patients with sickle cell disease. In this study, patients with SCD who would be expected to benefit from an allogeneic HCT will receive an unmanipulated peripheral blood derived hematopoietic stem and progenitor cell (HSPC) graft from either an MSD or HAPLO donor after a reduced intensity conditioning regimen comprising of alemtuzumab, thiotepa and low dose total body irradiation. All patients will receive a pre-conditioning phase comprising of hydroxyurea and azathioprine to reduce the risk of graft rejection. GVHD prophylaxis will consist of sirolimus. Patients on the HAPLO arm will also receive two doses of post-transplant cyclophosphamide. All patients will receive regularly scheduled low dose donor lymphocyte infusions till donor lymphocyte chimerism reaches at least 90% donor. The main objective of this study is to improve graft function and immune reconstitution after a reduced intensity conditioning based transplant.
1,104 studies on the registry are indexed under Anemia, Sickle Cell; 236 are open to participants now.
This study's enrollment of 46 is above the median of 40 across 750 interventional studies indexed under Anemia, Sickle Cell.
Browse Anemia, Sickle Cell studies →St. Jude Children's Research Hospital is the lead sponsor of 434 studies on the registry; 99 are open to participants now.
Of its 60 completed or terminated interventional studies of FDA-regulated products, 35 (58%) have results posted.
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Inclusion Criteria for Transplant Recipient
Patients with SCD (any genotype) who meet any ONE of the following criteria:
Exclusion Criteria for Transplant Recipient
HLA antibody presence and specificity will be determined by solid phase immunoassays. An anti-donor specific HLA antibody test will be considered positive when the mean fluorescence intensity (MFI) is:
A participant with presence of anti-donor specific HLA antibodies may be provisionally enrolled on the study if desensitization (see Appendix H) is begun concurrently with pre-conditioning. Response to desensitization will be defined as:
Inclusion Criteria for Donor
Patients with a suitable HLA matched sibling donor (MSD) will be enrolled on the MSD arm.
Drug: hydroxyurea, azathioprine, alemtuzumab, thioptepa, low dose total body irradiation and sirolimus
Patients without an eligible MSD who have a suitable haploidentical (HAPLO) donor available will be enrolled on the HAPLO arm of the study.
Drug: hydroxyurea, azathioprine, alemtuzumab, thiotepa, plerixafor, low dose total body irradiation, cyclophosphamide and sirolimus
The conditioning regimen will consist of hydroxyurea (30mg/Kg) and azathioprine (3mg/Kg) by mouth daily from day -60 to day -8, alemtuzumab subcutaneously daily for 5 days (0.03mg/kg on Day -7, 0.1mg/kg on Day -6, 0.3mg/kg on days -5 to -3), thiotepa intravenously (10mg/Kg) on day -3 and low dose total body irradiation (TBI) 200 cGY on day -2 with gonadal shielding (if possible). The HSCT graft will be G-CSF mobilized PBSCs with minimum CD34+ of 5 x10\^6/kg recipient weight. GVHD prophylaxis will be sirolimus with a loading dose 3 mg/m2 on day -1. Sirolimus dose will be adjusted to maintain a target trough level 5-15 ng/mL. Low dose donor lymphocyte infusions will begin on day +28 and continue till donor lymphocyte chimerism reaches at least 90% donor.
The conditioning regimen will consist of hydroxyurea (30mg/Kg) and azathioprine (3mg/Kg) by mouth daily from day -60 to day -8, alemtuzumab subcutaneously daily for 5 days (0.03mg/kg on Day -7, 0.1mg/kg on Day -6, 0.3mg/kg on days -5 to -3), thiotepa intravenously (10mg/Kg) on day -3, plerixafor (0.24mg/Kg) subcutaneously every 12 hours on days -3 and -2 and low dose total body irradiation (TBI) 200 cGY on days -2 and -1 with gonadal shielding (if possible). The HSCT graft will be G-CSF mobilized PBSCs with minimum CD34+ of 5 x10\^6/kg recipient weight. GVHD prophylaxis will be cyclophosphamide (50mg/Kg) intravenously on days +3 and +4 and sirolimus with a loading dose 3 mg/m2 starting on day +5. Sirolimus dose will be adjusted to maintain a target trough level 5-15 ng/mL. Low dose donor lymphocyte infusions will begin on day +28 and continue till donor lymphocyte chimerism reaches at least 90% donor.
Donor T-cell chimerism at 1-year post transplant in each respective arm (MSD, HAPLO) of the trial.
Number of participants who have achieved donor T-cell chimerism greater than 60% by 1-year post transplant will be reported. The rate of success will be checked for in each arm after the first 10 evaluable patients have been enrolled and followed for up to 1 year.
Time frame: 1 year after HCT
Overall survival and 1-year, 2-year and 3-year post-transplant graft versus host disease (GVHD)-free SCD-free survival.
Graft versus host disease (GVHD)-free SCD-free survival in each arm of the trial will be calculated at 1-year, 2-year and 3-year post-transplant and reported as a percentage of the enrolled patients.
Time frame: Up to 3 years after HCT
Graft rejection rate.
Primary and secondary graft rejection rate at 1-year, 2-year and 3-year post- transplant in each arm or the trial will be calculated and reported as a percentage of the enrolled patients.
Time frame: Up to 3 years after HCT
Incidence and severity of acute and chronic (GVHD).
The incidence and severity of acute and chronic (GVHD) in each arm or the trial will be calculated and reported as a percentage of the enrolled patients.
Time frame: Up to 3 years after HCT
Incidence of SCD recurrence after transplant.
The incidence of SCD recurrence after transplant in each arm or the trial will be calculated and reported as a percentage of the enrolled patients.
Time frame: Up to 3 years after HCT
Neutrophil and platelet recovery.
Number of patients who engraft their neutrophils and platelets by 6 months in each arm or the trial will be calculated and reported as a percentage of the enrolled patients.
Time frame: Up to 6 months after HCT
Plan to share: Yes — Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.
Supporting information: Study protocol, Sap
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