Haploidentical Donor Hematopoietic Cell Transplant for Sickle Cell Disease

The purpose of this study it to evaluate a reduced toxicity conditioning regimen for haploidentical donor HCT followed by a GVHD prophylaxis regimen comprising of post-transplant cyclophosphamide, sirolimus and abatacept with the goal to improve the GVHD-free rejection-free survival (GRFS) to greater than 90% after haploidentical donor HCT in children and young adults with SCD.

Primary Objective:

- To assess the GVHD-free and rejection free survival (GRFS) after haploidentical donor HCT in children and young adults with SCD.

Secondary Objectives:

• Assess the overall survival (OS) and disease-free survival (DFS) after haploidentical donor HCT for SCD.
• Estimate incidence and severity of acute and chronic GVHD after haploidentical donor HCT for SCD.
• Assess the neutrophil and platelet engraftment kinetics after haploidentical donor HCT for SCD.

Study Overview

• Status: Not yet recruiting
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: Alemtuzumab; Drug: Thiotepa; Drug: Filgrastim; Drug: Cyclophosphamide 50mg; Drug: Abatacept; Drug: Hydroxyurea; Drug: Sirolimus; Drug: Azathioprine; Radiation: TBI; Procedure: Hematopoietic Progenitor Cell Infusion

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Akshay Sharma, MD; Phone Number: 8662785833; Email: referralinfo@stjude.org

Study Locations

• United States
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St Jude Children's Research Hospital
      • Principal Investigator: Akshay Sharma, MD
      • Contact: Akshay Sharma, MD; Phone Number: 866-278-5833; Email: referralinfo@stjude.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Transplant Recipient

• Age less than or equal to 22 years.
• Patients without a suitable HLA-matched sibling donor but with a suitable single haplotype matched (≥ 3 of 6) family member donor. Potential donors do not need to undergo eligibility determination prior to the recipients enrolling on the study. As long as a potential donor is identified and willing to donate hematopoietic progenitor cells, recipients can enroll on the study.
• Patients with SCD (any genotype) who meet any ONE of the following criteria:
• History of an abnormal transcranial Doppler measurement defined as TCD velocity ≥200 cm/sec by the non-imaging technique (or ≥185 cm/sec by the imaging technique) measured at a minimum of two separate occasions.
• History of cerebral infarction on brain MRI (overt stroke, or silent cerebral infarct).
• History of two or more episodes of acute chest syndrome (ACS) in the 2-years period preceding enrollment.
• History of two or more SCD related pain events requiring treatment with parenteral analgesics in the last 12 months.
• History of two or more episodes of priapism (erection lasting ≥4 hours or requiring emergent medical care).
• Administration of regular RBC transfusions (≥8 transfusions in the previous 12 months).
• Evidence of progressive end organ damage (eg. cardiomyopathy, nephropathy, pulmonary hypertension etc) that in the opinion of the treating hematologist is not responsive to medical management and may benefit from an HCT. Such a determination must be made in writing by at least two independent hematologists and documented in the patient's electronic medical record prior to enrollment.

Donor

• An at least single haplotype matched (≥ 3 of 6) family member.
• HIV negative
• Not pregnant, as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment (if female).
• Not breast feeding.
• Donor should not have clinically significant hemoglobinopathy. Donors with sickle cell trait are acceptable.
• Regarding donation eligibility, is identified as either:
• Completed the process of donor eligibility determination as outlined in 21 CFR 1271 and agency guidance; OR.
• Does not meet 21 CFR 1271 eligibility requirements but has a declaration of urgent medical need completed by the principal investigator or physician sub-investigator per 21 CFR 1271.

Exclusion Criteria:

Transplant Recipient

• Karnofsky or Lansky performance score <60.
• Pregnant, as confirmed by positive serum or urine pregnancy test within 14 days prior to enrollment (if female).
• Breast feeding.
• Uncontrolled bacterial, viral or fungal infections (undergoing appropriate treatment and with progression of clinical symptoms) within 1 month prior to conditioning. Patients with febrile illness or suspected minor infection should await clinical resolution prior to starting conditioning. Patients with confirmed seropositivity or positive NAAT for HIV are excluded.
• Serum conjugated (direct) bilirubin >3x upper limit of normal for age as per local laboratory. Participants with hyperbilirubinemia as the result of hyperhemolysis, or a severe drop in hemoglobin post blood transfusion, are not excluded as long as it downtrends and return to acceptable limits subsequently.
• Left ventricular shortening fraction <25% or ejection fraction <40% by echocardiogram.
• Estimated creatinine clearance less than 50 mL/min/1.73m2.
• Diffusion capacity of carbon monoxide (DLCO) <35% (adjusted for hemoglobin) OR baseline oxygen saturation <85% or PaO2 <70.
• Presence of anti-donor specific HLA antibodies unresponsive to desensitization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HAPSCD Treatment	Drug: Alemtuzumab; IV; Drug: Thiotepa; IV; Drug: Filgrastim; IV; Drug: Cyclophosphamide 50mg; IV; Drug: Abatacept; IV; Drug: Hydroxyurea; IV; Drug: Sirolimus; IV; Drug: Azathioprine; IV; Radiation: TBI; Radiaiton therapy; Procedure: Hematopoietic Progenitor Cell Infusion; Hematopoietic Progenitor Cell Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GVHD-free and rejection free survival (GRFS)	GRFS is defined as the time interval from transplant (graft infusion) until the first of grade III-IV acute GVHD, moderate or severe chronic GVHD, primary or secondary graft failure requiring second definitive therapy, and death occurs. GRFS will be calculated at 1-year, and 3-year post-transplant and reported as a percentage of the enrolled patients.	Up to 3 years after HCT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Event for OS will include death due to any cause. OS will be evaluated and reported at 1 year and 3 years after HCT as a percentage of the enrolled patients.	Up to 3 years after HCT
Disease-free survival (DFS)	Events for DFS will include death due to any cause and recurrence of SCD symptoms or graft failure after HCT. DFS will be evaluated and reported at 1 year and 3 years after HCT as a percentage of the enrolled patients.	Up to 3 years after HCT
Incidence and severity of acute and chronic GVHD	Incidence of acute GVHD will be evaluated and reported at 1 month and, 3 months, and 6 months after HCT as a percentage of the enrolled patients. Incidence of chronic GVHD will be evaluated and reported at 6 months, 1 year and 3 years after HCT as a percentage of the enrolled patients	Up to 3 years after HCT
Neutrophil and platelet engraftment	The time to neutrophil and platelet engraftment will be reported in aggregate for all the participants using summary statistics.	Up to 6 months after HCT

Collaborators and Investigators

• Sponsor: St. Jude Children's Research Hospital
• Investigators: Principal Investigator: Akshay Sharma, MD, St. Jude Children's Research Hospital

Publications and helpful links

Helpful Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2034
• Study Completion (Estimated): September 1, 2035

Study Registration Dates

• First Submitted: May 17, 2026
• First Submitted That Met QC Criteria: May 27, 2026
• First Posted (Actual): June 1, 2026

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Hematopoietic Cell Transplant; Sickle Cell
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell; Immunoconjugates; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons; Biological Factors; Carbohydrates; Amides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Purines; Macrolides; Lactones; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Nucleosides; Intercellular Signaling Peptides and Proteins; Glycoproteins; Glycoconjugates; Triethylenephosphoramide; Aziridines; Azirines; Colony-Stimulating Factors; Hematopoietic Cell Growth Factors; Cytokines; Granulocyte Colony-Stimulating Factor; Urea; Thionucleosides; Mercaptopurine; Abatacept; Alemtuzumab; Sirolimus; Cyclophosphamide; Thiotepa; Azathioprine; Hydroxyurea; Filgrastim
• Other Study ID Numbers: HAPSCD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Time Frame: Data will be made available at the time of article publication.
• IPD Sharing Access Criteria: Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No