Haploidentical stem cell transplantation for adults with severe sickle cell disease

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

This study is testing if a special type of stem cell transplant can help adults with severe sickle cell disease who haven't found relief with other treatments.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: King's College Hospital NHS Trust (Academic / other)
• Locations: 1 site (London)
• Trial ID: NCT05392894 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness and cost-effectiveness of haploidentical stem cell transplantation (SCT) in adults suffering from severe sickle cell disease (SCD) who have not responded to other treatments or are intolerant to them. The study focuses on patients who are at high risk for complications and may require chronic transfusions. Participants will receive haploidentical SCT along with standard medical care to assess improvements in their condition and overall health outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with severe sickle cell disease who have a confirmed haploidentical donor.

Not a fit: Patients with mild sickle cell disease or those who do not have a suitable haploidentical donor may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve the quality of life and health outcomes for adults with severe sickle cell disease.

How similar studies have performed: Other studies have shown promise with haploidentical stem cell transplantation in similar patient populations, indicating potential for success in this approach.

Eligibility criteria

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.

Where this trial is running

London

• King's College Hospital — London, United Kingdom (Recruiting)

Study contacts

• Study coordinator: Victoria Potter, BSc, MBBS, FRACP, FRCPA

Conditions Sickle Cell Disease; Sickle; Haploidentical; Stem cell; Transplant