Haploidentical Donor Hematopoietic Cell Transplant for Sickle Cell Disease

NCT07616154 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HAPSCD
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Sickle Cell Disease

Keywords

Sickle Cell; Hematopoietic Cell Transplant

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Overall survival (OS)

  Up to 3 years after HCT

• Disease-free survival (DFS)

  Up to 3 years after HCT

• Incidence and severity of acute and chronic GVHD

  Up to 3 years after HCT

• Neutrophil and platelet engraftment

  Up to 6 months after HCT

Study Arms (1)

HAPSCD Treatment

EXPERIMENTAL

Drug: Cyclophosphamide 50mg; Drug: Abatacept; Drug: Alemtuzumab; Drug: Hydroxyurea; Drug: Thiotepa; Drug: Filgrastim; Drug: Sirolimus; Drug: Azathioprine; Radiation: TBI; Procedure: Hematopoietic Progenitor Cell Infusion

Interventions

Cyclophosphamide 50mg DRUG

IV

HAPSCD Treatment

Abatacept DRUG

IV

HAPSCD Treatment

Alemtuzumab DRUG

IV

HAPSCD Treatment

Hydroxyurea DRUG

IV

HAPSCD Treatment

Thiotepa DRUG

IV

HAPSCD Treatment

Filgrastim DRUG

IV

HAPSCD Treatment

Sirolimus DRUG

IV

HAPSCD Treatment

Azathioprine DRUG

IV

HAPSCD Treatment

TBI RADIATION

Radiaiton therapy

HAPSCD Treatment

Hematopoietic Progenitor Cell Infusion PROCEDURE

Hematopoietic Progenitor Cell Infusion

HAPSCD Treatment

Eligibility Criteria

• Age: Up to 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead

Study Sites (1)

St Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

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

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Cyclophosphamide; Abatacept; Alemtuzumab; Hydroxyurea; Thiotepa; Filgrastim; Sirolimus; Azathioprine

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Immunoproteins; Urea; Amides; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Macrolides; Lactones; Thionucleosides; Sulfur Compounds; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Akshay Sharma, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Akshay Sharma, MD

CONTACT

8662785833; referralinfo@stjude.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2026
• First Posted: June 1, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2034
• Study Completion (Estimated): September 1, 2035
• Last Updated: June 1, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available at the time of article publication.
• 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.

Locations

US (1)