Clinical trial NCT05392894: RElated Haplo-DonoR Haematopoietic stEm Cell Transplantation for Adults With Severe Sickle Cell Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Sickle Cell Disease
Keywords: Sickle
Haploidentical
Stem cell
Transplant
Lead sponsor: King's College Hospital NHS Trust
Sponsor class: OTHER
Collaborators: name: King's College London
name: University of Sheffield
name: Sheffield Teaching Hospitals NHS Foundation Trust
name: Imperial College Healthcare NHS Trust
name: Guy's and St Thomas' NHS Foundation Trust
name: University College London Hospitals
name: Manchester University NHS Foundation Trust
name: St George's University Hospitals NHS Foundation Trust
name: Barts & The London NHS Trust
name: National Institute for Health Research, United Kingdom
First posted: 2022-05-26
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Treatment failure or mortality
timeFrame: 24 months post-randomisation
Secondary outcomes:
measure: Health related quality of life
timeFrame: At 3, 6, 9, 12, 15, 18, 21 and 24 months post-randomisation
measure: All cause mortality
timeFrame: 24 months post-randomisation
measure: Sickle Cell Disease-related mortality (excluding transplant related complications)
timeFrame: 24 months post-randomisation
measure: Sickle type haemoglobin percentage (HbS%)
timeFrame: At 6, 12 and 24 months post-randomisation
measure: Sickle cell disease related complications
timeFrame: 24 months post-randomisation
measure: Haemoglobin levels, Reticulocyte count, LDH, Bilirubin
timeFrame: At 6, 12 and 24 months post-randomisation
measure: Pulmonary Function
timeFrame: At 12 months and 24 months post-randomisation
measure: Renal Function
timeFrame: At 6, 12 and 24 months post-randomisation
measure: Iron overload
timeFrame: 24 months post-randomisation
measure: Cardiac function and pulmonary hypertension
timeFrame: At 12 and 24 months post-randomisation
measure: Cerebrovascular progression
timeFrame: 24 months post-randomisation
measure: Evidence of hepatic progression
timeFrame: 24 months post-randomisation
measure: Percentage of participants requiring opioid use for pain related to vaso-occlusive sickle related crisis
timeFrame: At 12 and 24 months post-randomisation
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: King's College Hospital
Study officials:
affiliation: King's College Hospitals NHS Foundation Trust
name: Ann-Marie Murtagh
role: STUDY_DIRECTOR
References: