Sickle Cell Disease
Conditions
Keywords
Sickle, Haploidentical, Stem cell, Transplant
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.
Interventions
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.
Sponsors
King's College London
University of Sheffield
Sheffield Teaching Hospitals NHS Foundation Trust
Imperial College Healthcare NHS Trust
Guy's and St Thomas' NHS Foundation Trust
University College London Hospitals
Manchester University NHS Foundation Trust
St George's University Hospitals NHS Foundation Trust
Barts & The London NHS Trust
National Institute for Health Research, United Kingdom
King's College Hospital NHS Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adult patients age ≥ 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: 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 criteria
1. Fully matched sibling donor. 2. Previous bone marrow transplant. 3. Pregnancy or breast feeding. 4. Participants able to conceive a child that 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| All cause mortality | 24 months post-randomisation | Death by any cause |
| Sickle Cell Disease-related mortality (excluding transplant related complications) | 24 months post-randomisation | Death due to any sickle cell disease related cause |
| 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 complications | 24 months post-randomisation | Defined as transfusion requirement, painful VOC, stroke, pulmonary hypertension |
| Haemoglobin levels, Reticulocyte count, LDH, Bilirubin | At 6, 12 and 24 months post-randomisation | — |
| Pulmonary Function | At 12 months and 24 months post-randomisation | As measured by FEV1 %, FEV1/FVC ratio, TLCO % |
| 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 |
| Cerebrovascular progression | 24 months post-randomisation | As measured by clinical stroke or evidence of progression on MRI/MRA |
| 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 | — |
| Renal Function | At 6, 12 and 24 months post-randomisation | As measured by urea, creatinine and eGFR |
Countries
United Kingdom
Contacts
Primary ContactVictoria Potter, BSc, MBBS, FRACP, FRCPA
Backup ContactDaryl Hagan, BSc, MSc
Outcome results
None listed