RElated haplo-DonoR haematopoietic stEm cell transplantation for adults with Severe Sickle cell disease

Not Applicable

• Conditions: Sickle cell disease; Circulatory System

• Registration Number: ISRCTN90484310
• Lead Sponsor: King's College Hospital NHS Foundation Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-10-25
• Last Update Posted: 13 March 2023
• Study Completion: 2027-06-30

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1. Adult patients aged > = 18 years

2. Confirmed haploidentical donor

3. Severe SCD phenotype who are at high risk for morbidity and mortality. Severe SCD is defined by at least one of the following:
3.1. Clinically significant neurologic event (stroke) or deficit lasting > 24 hours
3.2. History of > = 2 acute chest syndromes in a 2-year period preceding enrolment despite optimum treatment, e.g. with hydroxycarbamide (HC)
3.3. 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)
3.4. Administration of regular transfusion therapy (=8 packed red blood transfusions per year for 1 year to prevent vaso-occlusive complications).
3.5. Patients assessed as requiring transfusion but with red cell alloantibodies/very rare blood type, rendering it difficult to continue/commence chronic transfusion
3.6. Patients requiring HC/transfusion for treatment of SCD complications who cannot tolerate either therapy due to significant adverse reactions
3.7. 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.

4. Patients must be fit to proceed to Haploidentical SCT as defined below:
4.1. Karnofsky score > = 60
4.2. Cardiac function: LVEF > = 45% or shortening fraction > = 25%
4.3. Lung Function: FEV1, FVC and TLCO > = 50%
4.4. Renal function: EDTA GFR > = 40 ml/m2/1.73m2
4.5. 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.

5. Written informed consent

Exclusion Criteria

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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Treatment failure or mortality, defined as occurrence of vaso-occlusive crisis, or transfusion from 6 months post-randomisation, measured by accessing medical records by 24 months post-randomisation