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

Официальное название

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

Обзор

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.

Вмешательства

• Процедура Haploidentical stem cell transplantation
  Stem cell transplant from bone marrow or peripheral blood from haploidentical donor using standard nationally approved transplant procedure.
• Другое 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.

Первичные конечные точки

• Treatment failure or mortality [Срок оценки: 24 months post-randomisation]

Вторичные конечные точки (12)

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

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Великобритания · 1 центр

• King's College Hospital — London

Идентификаторы

NCT: NCT05392894 · IRAS: 312212

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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