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Recruiting NCT05392894

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

Phase III Interventional Sickle Cell Disease

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Haploidentical stem cell transplantation, Standard medical care.
Who it may be relevant to
Registry conditions: Sickle Cell Disease. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United Kingdom
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

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

Overview

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.

Interventions

  • 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.

Primary outcome measures

  • Treatment failure or mortality [Time frame: 24 months post-randomisation]
Secondary outcome measures (12)
  • Health related quality of life [Time frame: At 3, 6, 9, 12, 15, 18, 21 and 24 months post-randomisation]
  • All cause mortality [Time frame: 24 months post-randomisation]
  • Sickle Cell Disease-related mortality (excluding transplant related complications) [Time frame: 24 months post-randomisation]
  • Sickle type haemoglobin percentage (HbS%) [Time frame: At 6, 12 and 24 months post-randomisation]
  • Sickle cell disease related complications [Time frame: 24 months post-randomisation]
  • Haemoglobin levels, Reticulocyte count, LDH, Bilirubin [Time frame: At 6, 12 and 24 months post-randomisation]
  • Pulmonary Function [Time frame: At 12 months and 24 months post-randomisation]
  • Renal Function [Time frame: At 6, 12 and 24 months post-randomisation]
  • Iron overload [Time frame: 24 months post-randomisation]
  • Cardiac function and pulmonary hypertension [Time frame: At 12 and 24 months post-randomisation]
  • Cerebrovascular progression [Time frame: 24 months post-randomisation]
  • Evidence of hepatic progression [Time frame: 24 months post-randomisation]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Open label
Primary purpose
Treatment

Study locations

United Kingdom · 1 center
  • King's College Hospital — London

Identifiers

NCT: NCT05392894 · IRAS: 312212

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗