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

King's College Hospital NHS Trust

Status and phase: Enrolling; Phase 3

Conditions: Sickle Cell Disease

Treatments: Procedure: Haploidentical stem cell transplantation; Other: Standard medical care

Study type: Interventional

Funder types: Other

Identifiers

NCT05392894

IRAS: 312212

Details and patient eligibility

About

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.

Enrollment: 120 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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120 participants in 2 patient groups

Standard of care

Active Comparator group

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.

Treatment:

Other: Standard medical care

Haploidentical stem cell transplantation

Experimental group

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.

Treatment:

Procedure: Haploidentical stem cell transplantation