RecruitingPhase 3NCT05392894

RElated Haplo-DonoR Haematopoietic stEm Cell Transplantation for Adults With Severe Sickle Cell Disease

A Multi-centre Open Randomised Controlled Trial to Assess the Effect of Related Haplo-donor Haematopoietic Stem Cell Transplantation Versus Standard of Care (no Transplant) on Treatment Failure at 24 Month in Adults With Severe Sickle Cell Disease

Sponsor

King's College Hospital NHS Trust

Enrollment

120 participants

Start Date

Feb 23, 2023

Study Type

INTERVENTIONAL

Conditions

Sickle Cell Disease

Summary

The purpose of this clinical trial is to evaluate the clinical and cost effectiveness of Haploidentical Stem Cell Transplantation (SCT) for adults with severe sickle cell disease (SCD), who have failed other therapies or are intolerant of existing therapies or require chronic transfusions to prevent on-going complications of SCD.

Eligibility

Min Age: 18 Years

Inclusion Criteria12

Adult patients age ≥ 18 years
Confirmed haploidentical donor
Severe SCD phenotype who are at high risk for morbidity and mortality. Severe SCD is defined by at least one of the following:
i. Clinically significant neurologic event (stroke) or deficit lasting > 24 hours.
ii. History of ≥2 acute chest syndromes in a 2-year period preceding enrolment despite optimum treatment, e.g. with hydroxycarbamide (HC).
iii. History of ≥3 severe pain crises per year in a 2-year period preceding enrolment despite the institution of supportive care measures (e.g. optimum treatment with HC).
iv. Administration of regular transfusion therapy (=8 packed red blood transfusions per year for 1 year to prevent vaso-occlusive complications).
v. Patients assessed as requiring transfusion but with red cell allo-antibodies/very rare blood type, rendering it difficult to continue/commence chronic transfusion.
vi. Patients requiring HC/transfusion for treatment of SCD complications who cannot tolerate either therapy due to significant adverse reactions.
vii. Established end organ damage relating to SCD, including but not limited to progressive sickle vasculopathy and hepatopathy. End-organ sufficient for entry to this trial shall be ratified at the UK NHP.
d) Patients must be fit to proceed to Haploidentical SCT as defined below: i. Karnofsky score ≥60 ii. Cardiac function: LVEF ≥45% or shortening fraction ≥25% iii. Lung Function: FEV1, FVC and TLCO ≥50% iv. Renal function: EDTA GFR ≥40 ml/min/1.73m2 v. Hepatic function: ALT <x3 ULN and bilirubin <x2 the upper limit of normal, those with hyperbilirubinemia due to sickle related haemolysis will not be excluded. No radiological evidence of cirrhosis.
e) Written informed consent.

Exclusion Criteria9

Fully matched sibling donor.
Previous bone marrow transplant.
Pregnancy or breast feeding.
Participants able to conceive a child that are unprepared to use effective contraception.
Clinically significant donor specific HLA antibodies.
HIV infection or active Hepatitis B or C.
Uncontrolled infection including bacterial, fungal and viral.
Participation in another interventional trial in the last three months.
Pre-existing condition deemed to significantly increase the risk of Haploidentical SCT by the local Principal Investigator.

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Interventions

PROCEDUREHaploidentical stem cell transplantation

Stem cell transplant from bone marrow or peripheral blood from haploidentical donor using standard nationally approved transplant procedure.

OTHERStandard medical care

Standard medical care may include any currently available therapies for SCD patients. These may or may not include regular elective transfusion therapy or medications such as hydroxycarbamide.