|Jinmi BAEK, Master|
|+33 1 42 19 28 49|
|Marina CAVAZZANA, MD & PhD|
1 France site
12 to 20 Years
Phase 1/Phase 2
– Age 12-20 years
Diagnosis of HbSS or S-beta zero thalassemia by Hb electrophoresis or genetic analysis.
Clinical history or ongoing evidence of severe sickle cell anemia with one OR more of the following clinical complications demonstrating disease severity:
At least 3 vaso occlusive crises requiring hospitalization, under hydroxyurea or transfusion, within 2 years prior to enrollment
One severe acute chest syndrome (ACS) hospitalized in intensive care unit
At least 2 episodes of ACS within the prior 3 years), including one under HU.
Acute priapism (at least 2 episodes > 3h in the preceding year or in the year prior to the start of a regular transfusion program), OR stuttering priapism ≥ 1 by week under sickle cell treatment (HU, transfusion or phlebotomy).
Cerebral vasculopathy confirmed by MRA (magnetic resonance angiography) without Moya-moya
Presence of sickle cell cardiomyopathy documented by Doppler echocardiography (left ventricular ejection fraction (LVEF) <55% AND tricuspid regurgitation velocity >2.5m/s on cardiac echocardiograph),
Tricuspid regurgitation velocity >2.8m/s on cardiac echocardiograph without pulmonary hypertension confirmed by right heart catheterization (mPAP<25mmHg) Failed hydroxyurea (HU) therapy, were unable to tolerate HU therapy, or, if 18 years of age or older, have actively made the choice to not take the recommended daily HU regimen. Inadequate clinical response to HU, defined as any one of the following outcomes, while on HU for at least 3 months: 2 or more acute sickle pain crises requiring hospitalization, no rise in Hb >1.5 gm/dl from pre-HU baseline or requires transfusion to maintain Hb > 6.0 gm/dL, had an episode of ACS despite adequate supportive care measures.
Karnovsky/Lansky performance score ≥ 60%
Sexually active patients must be willing to use an acceptable method of double-barrier contraception for at least 12 months post-infusion (beyond 12 months at the discretion of the investigator)
Chromosomal (karyotyping) or molecular anomalies (detected by NGS) ( ie 7 chromosomal monosomy)
Existence of a matched sibling donor
Patients who have started new treatment for SCD within 6months of enrollment
Hematologic evaluation: Leukopenia (WBC < 3000 µL) ( en cours) or neutropenia (ANC < 1000 µL) or thrombocytopenia (platelet count < 100,000 µL) (not due to an erythropheresis procedure) PT/INR or PTT > 1.5 times upper limit of normal (ULN) or clinically significant bleeding disorder
Evaluations within 6 months prior to screening visit:
ALT or AST > 3 times ULN
Liver Cirrhosis suspicion on echography, CT scan or MRI AND confirmed by histology
Cardiac evaluation: LVEF < 40% by cardiac echocardiogram or by MUGA scan Stroke with significant CNS sequelae i.e., Rankin > 2
Lung interstitial infiltrate AND Forced Vital Capacity less than 70% AND DLCO less than 60% at steady state
Confirmed pulmonary hypertension defined by a right heart catheterization (PAPm>25mmHg). Right heart catheterization is required if tricuspid regurgitation velocity >2.8m/s on cardiac echocardiograph OR >2.5m/s with an abnormal Brain Natriuretic Peptide dosage or an important decrease in transcutaneous Hb O2 saturation during the 6 minutes walk test.
Seropositivity for HIV (Human Immunodeficiency Virus), HCV (Hepatitis C Virus), HTLV-1 (Human T-Lymphotropic Virus), or active Hepatitis B Virus, or active infection by CMV or parvovirus B19, based on positive blood PCR.
Pregnancy or breastfeeding in a postpartum female
Any current cancer or prior history of a malignant disease, with the exception of curatively treated non-melanoma skin cancer
Immediate family member with an established or suspected Familial Cancer Syndrome
Diagnosis of significant psychiatric disorder of the subject that could seriously impeded the ability to participate in the study
Patients who failed previous HSCT and are severely ill
Any clinically significant active infection
Participation in another clinical study with an investigational drug within 30 days of screening
Any condition, based on perspective of the medical monitor and treating investigator, which may lead to increased safety risk or inability to comply with the protocol