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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

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:

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.

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

NCT ID

NCT05392894

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

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

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

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

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

victoriapotter@nhs.net

First Name & Middle Initial & Last Name or Official Title & Degree

Daryl Hagan, BSc, MSc

Phone

+44 20 7848 0532

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

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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