Recruiting

Phase 2

HCT with Cyclophosphamide, Sirolimus, AbataceptHaploidentical Donor Hematopoietic Cell Transplant for Sickle Cell Disease

Sponsor:

St. Jude Children's Research Hospital

Code:

NCT07616154

Conditions

Sickle Cell Disease

Eligibility Criteria

Sex: All

Age: 0 - 22

Healthy Volunteers: Not accepted

Interventions

Cyclophosphamide 50mg

Abatacept

Alemtuzumab

Hydroxyurea

Thiotepa

Study Details

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

Study ID

NCT07616154

Start date

Sep, 2026

Status verified date

Jul, 2026

Completion date

Sep, 2035

Anticipated

Primary completion date

Sep, 2034

Anticipated

Eligibility Criteria

Sex: All

Age: 0 - 22

Healthy Volunteers: Not accepted

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 Design

Enrollment

45 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: HAPSCD Treatment

Interventions

Cyclophosphamide 50mg

Abatacept

Alemtuzumab

Hydroxyurea

Thiotepa

Filgrastim

Sirolimus

Azathioprine

TBI

Radiaiton therapy

Hematopoietic Progenitor Cell Infusion

Primary outcome measure

GVHD-free and rejection free survival (GRFS) [ Time Frame: Up to 3 years after HCT ]

Central Contacts and Locations

Central contacts

Akshay Sharma, MD

8662785833 referralinfo@stjude.org

Locations

St Jude Children's Research Hospital

Recruiting

Memphis, Tennessee, United States, 38105

Contacts

Akshay Sharma, MD

866-278-5833 referralinfo@stjude.org

Principal Investigator:

Akshay Sharma, MD

More Information

Sponsor

St. Jude Children's Research Hospital

Last update posted

Jul 23, 2026

Last verified

Jul, 2026

Keywords

Sickle Cell
Hematopoietic Cell Transplant

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by St. Jude Children's Research Hospital on 2026-07-23.