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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Other: Standard medical care; Procedure: Haploidentical stem cell transplantation

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Victoria Potter, BSc, MBBS, FRACP, FRCPA; Phone Number: +44 20 3299 3730; Email: victoriapotter@nhs.net
• Study Contact Backup: Name: Daryl Hagan, BSc, MSc; Phone Number: +44 20 7848 0532; Email: redress@kcl.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom
    • Recruiting
    • King's College Hospital
    • Principal Investigator: Victoria Potter
    • Contact: Victoria Potteer; Email: victoriapotter@nhs.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of 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.	Other: Standard 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.
Experimental: 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.	Procedure: Haploidentical stem cell transplantation; Stem cell transplant from bone marrow or peripheral blood from haploidentical donor using standard nationally approved transplant procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment failure or mortality	Treatment failure is defined as occurrence of vaso-occlusive crisis, or transfusion from 6 months post-randomisation.	24 months post-randomisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health related quality of life	Quality of life as measured by EQ-5D-5L	At 3, 6, 9, 12, 15, 18, 21 and 24 months post-randomisation
All cause mortality	Death by any cause	24 months post-randomisation
Sickle Cell Disease-related mortality (excluding transplant related complications)	Death due to any sickle cell disease related cause	24 months post-randomisation
Sickle type haemoglobin percentage (HbS%)	Sickle type haemoglobin as measured by haemoglobin electrophoresis	At 6, 12 and 24 months post-randomisation
Sickle cell disease related complications	Defined as transfusion requirement, painful VOC, stroke, pulmonary hypertension	24 months post-randomisation
Haemoglobin levels, Reticulocyte count, LDH, Bilirubin		At 6, 12 and 24 months post-randomisation
Pulmonary Function	As measured by FEV1 %, FEV1/FVC ratio, TLCO %	At 12 months and 24 months post-randomisation
Renal Function	As measured by urea, creatinine and eGFR	At 6, 12 and 24 months post-randomisation
Iron overload	As measured by Ferritin and FerriScan (R2-MRI)	24 months post-randomisation
Cardiac function and pulmonary hypertension	As measured by echocardiogram/TRV	At 12 and 24 months post-randomisation
Cerebrovascular progression	As measured by clinical stroke or evidence of progression on MRI/MRA	24 months post-randomisation
Evidence of hepatic progression	As measured by liver function (ALT, AST, ALP, GGT, Bilirubin) and FibroScan	24 months post-randomisation
Percentage of participants requiring opioid use for pain related to vaso-occlusive sickle related crisis		At 12 and 24 months post-randomisation

Collaborators and Investigators

• Sponsor: King's College Hospital NHS Trust
• Collaborators: King's College London; University College London Hospitals; University of Sheffield; Guy's and St Thomas' NHS Foundation Trust; Sheffield Teaching Hospitals NHS Foundation Trust; Barts & The London NHS Trust; Manchester University NHS Foundation Trust; National Institute for Health Research, United Kingdom; Imperial College Healthcare NHS Trust; St George's University Hospitals NHS Foundation Trust
• Investigators: Study Director: Ann-Marie Murtagh, King's College Hospitals NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2023
• Primary Completion (Anticipated): March 1, 2027
• Study Completion (Anticipated): March 1, 2027

Study Registration Dates

• First Submitted: May 23, 2022
• First Submitted That Met QC Criteria: May 23, 2022
• First Posted (Actual): May 26, 2022

Study Record Updates

• Last Update Posted (Actual): May 10, 2023
• Last Update Submitted That Met QC Criteria: May 9, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Transplant; Haploidentical; Stem cell; Sickle
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: IRAS: 312212

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No