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

Sickle Cell Disease Clinical Trial

— REDRESS  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05392894
• Other study ID #: IRAS: 312212
• Status: Recruiting
• Phase: Phase 3
• Start date: February 23, 2023
• Est. completion date: March 2027

Study information

• Verified date: May 2023
• Source: King's College Hospital NHS Trust
• Contact: Victoria Potter, BSc, MBBS, FRACP, FRCPA
• Phone: +44 20 3299 3730
• Email: victoriapotter[@]nhs.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: March 2027
• Est. primary completion date: March 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Procedure:
• Haploidentical stem cell transplantation
Stem cell transplant from bone marrow or peripheral blood from haploidentical donor using standard nationally approved transplant procedure.

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.

Locations

Country	Name	City	State
United Kingdom	King's College Hospital	London

Sponsors (11)

Lead Sponsor

Collaborator

King's College Hospital NHS Trust

Barts & The London NHS Trust, Guy's and St Thomas' NHS Foundation Trust, Imperial College Healthcare NHS Trust, King's College London, Manchester University NHS Foundation Trust, National Institute for Health Research, United Kingdom, Sheffield Teaching Hospitals NHS Foundation Trust, St George's University Hospitals NHS Foundation Trust, University College London Hospitals, University of Sheffield

Country where clinical trial is conducted

United Kingdom, 

Outcome

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