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

Primary Purpose

Sickle Cell Disease

Status
Recruiting
Phase
Phase 3
Locations
United Kingdom
Study Type
Interventional
Intervention
Haploidentical stem cell transplantation
Standard medical care
Sponsored by
King's College Hospital NHS Trust
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sickle Cell Disease focused on measuring Sickle, Haploidentical, Stem cell, Transplant

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • King's College HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Standard of care

Haploidentical stem cell transplantation

Arm Description

The comparator arm is standard medical care for this patient population. Standard medical care may include all currently available non-trial therapies for SCD.

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.

Outcomes

Primary Outcome Measures

Treatment failure or mortality
Treatment failure is defined as occurrence of vaso-occlusive crisis, or transfusion from 6 months post-randomisation.

Secondary Outcome Measures

Health related quality of life
Quality of life as measured by EQ-5D-5L
All cause mortality
Death by any cause
Sickle Cell Disease-related mortality (excluding transplant related complications)
Death due to any sickle cell disease related cause
Sickle type haemoglobin percentage (HbS%)
Sickle type haemoglobin as measured by haemoglobin electrophoresis
Sickle cell disease related complications
Defined as transfusion requirement, painful VOC, stroke, pulmonary hypertension
Haemoglobin levels, Reticulocyte count, LDH, Bilirubin
Pulmonary Function
As measured by FEV1 %, FEV1/FVC ratio, TLCO %
Renal Function
As measured by urea, creatinine and eGFR
Iron overload
As measured by Ferritin and FerriScan (R2-MRI)
Cardiac function and pulmonary hypertension
As measured by echocardiogram/TRV
Cerebrovascular progression
As measured by clinical stroke or evidence of progression on MRI/MRA
Evidence of hepatic progression
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

Full Information

First Posted
May 23, 2022
Last Updated
May 9, 2023
Sponsor
King's College Hospital NHS Trust
Collaborators
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
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1. Study Identification

Unique Protocol Identification Number
NCT05392894
Brief Title
RElated Haplo-DonoR Haematopoietic stEm Cell Transplantation for Adults With Severe Sickle Cell Disease
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 23, 2023 (Actual)
Primary Completion Date
March 2027 (Anticipated)
Study Completion Date
March 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
King's College Hospital NHS Trust
Collaborators
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

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease
Keywords
Sickle, Haploidentical, Stem cell, Transplant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Standard of care
Arm Type
Active Comparator
Arm Description
The comparator arm is standard medical care for this patient population. Standard medical care may include all currently available non-trial therapies for SCD.
Arm Title
Haploidentical stem cell transplantation
Arm Type
Experimental
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Haploidentical stem cell transplantation
Intervention Description
Stem cell transplant from bone marrow or peripheral blood from haploidentical donor using standard nationally approved transplant procedure.
Intervention Type
Other
Intervention Name(s)
Standard medical care
Intervention Description
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.
Primary Outcome Measure Information:
Title
Treatment failure or mortality
Description
Treatment failure is defined as occurrence of vaso-occlusive crisis, or transfusion from 6 months post-randomisation.
Time Frame
24 months post-randomisation
Secondary Outcome Measure Information:
Title
Health related quality of life
Description
Quality of life as measured by EQ-5D-5L
Time Frame
At 3, 6, 9, 12, 15, 18, 21 and 24 months post-randomisation
Title
All cause mortality
Description
Death by any cause
Time Frame
24 months post-randomisation
Title
Sickle Cell Disease-related mortality (excluding transplant related complications)
Description
Death due to any sickle cell disease related cause
Time Frame
24 months post-randomisation
Title
Sickle type haemoglobin percentage (HbS%)
Description
Sickle type haemoglobin as measured by haemoglobin electrophoresis
Time Frame
At 6, 12 and 24 months post-randomisation
Title
Sickle cell disease related complications
Description
Defined as transfusion requirement, painful VOC, stroke, pulmonary hypertension
Time Frame
24 months post-randomisation
Title
Haemoglobin levels, Reticulocyte count, LDH, Bilirubin
Time Frame
At 6, 12 and 24 months post-randomisation
Title
Pulmonary Function
Description
As measured by FEV1 %, FEV1/FVC ratio, TLCO %
Time Frame
At 12 months and 24 months post-randomisation
Title
Renal Function
Description
As measured by urea, creatinine and eGFR
Time Frame
At 6, 12 and 24 months post-randomisation
Title
Iron overload
Description
As measured by Ferritin and FerriScan (R2-MRI)
Time Frame
24 months post-randomisation
Title
Cardiac function and pulmonary hypertension
Description
As measured by echocardiogram/TRV
Time Frame
At 12 and 24 months post-randomisation
Title
Cerebrovascular progression
Description
As measured by clinical stroke or evidence of progression on MRI/MRA
Time Frame
24 months post-randomisation
Title
Evidence of hepatic progression
Description
As measured by liver function (ALT, AST, ALP, GGT, Bilirubin) and FibroScan
Time Frame
24 months post-randomisation
Title
Percentage of participants requiring opioid use for pain related to vaso-occlusive sickle related crisis
Time Frame
At 12 and 24 months post-randomisation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Victoria Potter, BSc, MBBS, FRACP, FRCPA
Phone
+44 20 3299 3730
Email
victoriapotter@nhs.net
First Name & Middle Initial & Last Name or Official Title & Degree
Daryl Hagan, BSc, MSc
Phone
+44 20 7848 0532
Email
redress@kcl.ac.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ann-Marie Murtagh
Organizational Affiliation
King's College Hospitals NHS Foundation Trust
Official's Role
Study Director
Facility Information:
Facility Name
King's College Hospital
City
London
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Victoria Potteer
Email
victoriapotter@nhs.net
First Name & Middle Initial & Last Name & Degree
Victoria Potter

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

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

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