RElated Haplo-DonoR Haematopoietic stEm Cell Transplantation for Adults With Severe Sickle Cell Disease
- Conditions
- Sickle Cell Disease
- Interventions
- Other: Standard medical careProcedure: Haploidentical stem cell transplantation
- Registration Number
- NCT05392894
- Lead Sponsor
- King's College Hospital NHS Trust
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 120
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standard of care Standard medical care The comparator arm is standard medical care for this patient population. Standard medical care may include all currently available non-trial therapies for SCD. Haploidentical stem cell transplantation Haploidentical stem cell transplantation Participants receiving Haploidentical Stem Cell Transplantation will receive the transplant conditioning regimen as per the standard transplant protocol. Stem cells from a haploidentical donor will be infused on Day 0 according to standard institutional practices. Bone marrow is the preferred stem cell source however peripheral blood may be used as an alternative where required due to donor reasons.
- Primary Outcome Measures
Name Time Method Treatment failure or mortality 24 months post-randomisation Treatment failure is defined as occurrence of vaso-occlusive crisis, or transfusion from 6 months post-randomisation.
- Secondary Outcome Measures
Name Time Method Sickle cell disease related complications 24 months post-randomisation Defined as transfusion requirement, painful VOC, stroke, pulmonary hypertension
Renal Function At 6, 12 and 24 months post-randomisation As measured by urea, creatinine and eGFR
Sickle type haemoglobin percentage (HbS%) At 6, 12 and 24 months post-randomisation Sickle type haemoglobin as measured by haemoglobin electrophoresis
Sickle Cell Disease-related mortality (excluding transplant related complications) 24 months post-randomisation Death due to any sickle cell disease related cause
Haemoglobin levels, Reticulocyte count, LDH, Bilirubin At 6, 12 and 24 months post-randomisation All cause mortality 24 months post-randomisation Death by any cause
Pulmonary Function At 12 months and 24 months post-randomisation As measured by FEV1 %, FEV1/FVC ratio, TLCO %
Cerebrovascular progression 24 months post-randomisation As measured by clinical stroke or evidence of progression on MRI/MRA
Health related quality of life At 3, 6, 9, 12, 15, 18, 21 and 24 months post-randomisation Quality of life as measured by EQ-5D-5L
Iron overload 24 months post-randomisation As measured by Ferritin and FerriScan (R2-MRI)
Cardiac function and pulmonary hypertension At 12 and 24 months post-randomisation As measured by echocardiogram/TRV
Evidence of hepatic progression 24 months post-randomisation As measured by liver function (ALT, AST, ALP, GGT, Bilirubin) and FibroScan
Percentage of participants requiring opioid use for pain related to vaso-occlusive sickle related crisis At 12 and 24 months post-randomisation
Trial Locations
- Locations (1)
King's College Hospital
🇬🇧London, United Kingdom