Table 1. Staged pediatric eligibility... | American Society of Hematology

Table 1.

Staged pediatric eligibility criteria of the phase 2 trial

Protocol version release date	Indication	Definitions of SCD-specific eligibility indications
V1.0 25 April 2017	Stroke	A neurological event resulting in focal neurologic deficits that lasted ≥24 h (classical clinical definition of stroke, not requiring imaging studies of the brain) or a focal neurological event resulting in abnormalities on T2-weighted or FLAIR images using an MRI scan, indicative of an acute infarct, with no other reasonable medical explanation (definition of a stroke supported with MRI imaging scans of the brain) or both.
V2.0 12 January 2018		Updated the definition of stroke to provide additional detail regarding the requirements for documenting a stroke.
V3.0 13 December 2018	Nonstroke neurologic changes requiring chronic transfusion therapy	Expanded pediatric stroke eligibility criteria to include patients with abnormal TCD or SCI requiring chronic transfusions. aTCD measurement with a timed average maximum mean velocity of >200 cm/sec in the terminal portion of the internal carotid or proximal portion of the middle cerebral artery1 or if the imaging TCD method is used >185 cm/sec plus evidence of intracranial vasculopathy. SCI defined as an infarct-like lesion based on an MRI signal abnormality at least 3 mm in 1 dimension and visible in 2 planes on FLAIR or T2- weighted images (or similar image with 3-dimentional imaging) and documented neurological examination performed by a neurologist demonstrating the participant has a normal neurologic examination or an abnormality on examination that could not be explained by the location of the brain lesion(s).
V4.0 3 December 2019		Clarification to stroke eligibility criteria to exclude patients with overt stroke, transient ischemic attack, or EDAS within 180 d before enrollment.
V5.0 19 May 2021	Nonneurologic changes	Expanded pediatric eligibility criteria beyond neurological indications 1 ACS episode resulting in intensive care admission requiring nonmechanical ventilatory support: simple nasal cannula, face mask that requires oxygen content (venti mask and nonrebreather), simple nasal cannula, face mask O2 (eg, venti mask and rebreather), CPAP, SiPAP, BiPAP, HFNC, or invasive mechanical ventilatory support (delivered by an endotracheal tube or tracheostomy). Right heart catheterization confirmed pulmonary artery pressure >25 mmHg or mean pulmonary vascular resistance 206 (57-421) dyn·s·cm^–5. Essential hypertension on antihypertensive medications >95% upper limit of normal age (as defined by the AAP). Acute severe VOP episodes requiring hospitalization and recalcitrant to maximum medical therapy. Episodes of pain to be adjudicated by selected committee. Recurrent priapism (episodes lasting at least 4 h and at least twice in the last 12 mo or 3 times in the last 24 mo) recalcitrant to medical treatment or unable to use hydroxyurea due to SCD phenotype with the approval of the adjudication committee.

Protocol version release date	Indication	Definitions of SCD-specific eligibility indications
V1.0 25 April 2017	Stroke	A neurological event resulting in focal neurologic deficits that lasted ≥24 h (classical clinical definition of stroke, not requiring imaging studies of the brain) or a focal neurological event resulting in abnormalities on T2-weighted or FLAIR images using an MRI scan, indicative of an acute infarct, with no other reasonable medical explanation (definition of a stroke supported with MRI imaging scans of the brain) or both.
V2.0 12 January 2018		Updated the definition of stroke to provide additional detail regarding the requirements for documenting a stroke.
V3.0 13 December 2018	Nonstroke neurologic changes requiring chronic transfusion therapy	Expanded pediatric stroke eligibility criteria to include patients with abnormal TCD or SCI requiring chronic transfusions. aTCD measurement with a timed average maximum mean velocity of >200 cm/sec in the terminal portion of the internal carotid or proximal portion of the middle cerebral artery1 or if the imaging TCD method is used >185 cm/sec plus evidence of intracranial vasculopathy. SCI defined as an infarct-like lesion based on an MRI signal abnormality at least 3 mm in 1 dimension and visible in 2 planes on FLAIR or T2- weighted images (or similar image with 3-dimentional imaging) and documented neurological examination performed by a neurologist demonstrating the participant has a normal neurologic examination or an abnormality on examination that could not be explained by the location of the brain lesion(s).
V4.0 3 December 2019		Clarification to stroke eligibility criteria to exclude patients with overt stroke, transient ischemic attack, or EDAS within 180 d before enrollment.
V5.0 19 May 2021	Nonneurologic changes	Expanded pediatric eligibility criteria beyond neurological indications 1 ACS episode resulting in intensive care admission requiring nonmechanical ventilatory support: simple nasal cannula, face mask that requires oxygen content (venti mask and nonrebreather), simple nasal cannula, face mask O2 (eg, venti mask and rebreather), CPAP, SiPAP, BiPAP, HFNC, or invasive mechanical ventilatory support (delivered by an endotracheal tube or tracheostomy). Right heart catheterization confirmed pulmonary artery pressure >25 mmHg or mean pulmonary vascular resistance 206 (57-421) dyn·s·cm^–5. Essential hypertension on antihypertensive medications >95% upper limit of normal age (as defined by the AAP). Acute severe VOP episodes requiring hospitalization and recalcitrant to maximum medical therapy. Episodes of pain to be adjudicated by selected committee. Recurrent priapism (episodes lasting at least 4 h and at least twice in the last 12 mo or 3 times in the last 24 mo) recalcitrant to medical treatment or unable to use hydroxyurea due to SCD phenotype with the approval of the adjudication committee.

BMT CTN 1507 phase 2 HLA-haploidentical hematopoietic cell trial (NCT03263559) protocol versions describing the staged additions to eligibility.

AAP, American Academy of Pediatrics; aTCD, abnormal TCD; BiPAP, bilevel positive airway pressure; CPAP, continuous positive airway pressure; EDAS, encephaloduroarteriosynangiosis; FLAIR, fluid-attenuated inversion recovery; HFNC, high-flow nasal cannula; MRI, magnetic resonance imaging; SiPAP, synchronized inspiratory positive airway pressure; VOP, vaso-occlusive pain.

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