This is a phase I, open label study to evaluate the safety, identify the recommended dose (RD) and obtain preliminar evidence of the efficacy of allogeneic, CD19-directed Chimeric Antigen Receptor T (alloCAR-T) cells in pediatric and young adults patients with relapsed/refractory B-cell precursor Acute Lymphoblastic Leukemia (BCP-ALL).
This is a phase 1, single-center, non-randomized, open-label, dose-escalation study to evaluate the safety, identify the recommended dose (RD) and obtain preliminar evidence of the efficacy of fresh, donor-derived, CD19-directed-second-generation CAR T cells (alloCART) in pediatric and young adults patients with relapsed/refractory B-cell precursor Acute Lymphoblastic Leukemia (BCP-ALL) occurring either after allogeneic hematopoietic stem cell transplantation (alloHSCT) or before alloHSCT, in case of refractory disease and availability of a HLA-fully matched donor.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Biological/Vaccine: CD19-CAR\_Lenti\_ALLO A single infusion of CD19-CAR\_Lenti\_ALLO on Day 0
Ospedale Pediatrico Bambino Gesù
Rome, Italy, Italy
RECRUITINGSafety and establishment of Dose limited Toxicity (DLT) of the infusion of CD19-CAR_Lenti_ALLO cells in pediatric and young adults patients affected by relapsed/refractory BCP-ALL in each dose level
DLT is defined as any of the following events: (1) Grade III-IV GvHD refractory to first and second line treatment and chronic GvHD refractory to first and second-ine treatment; (2) any grade 4 non-hematologic toxicity; (3) grade 4 reactions realted to anti-alloCART infusion; (4) death related to alloCART infusion. The Maximum Tolerated Dose/Recommended Dose (MTD/RD) of CD19-CAR\_Lenti\_ALLO to be evaluated for efficacy in the phase II extension will be defined as the highest dose level at which \<33% of patients (no more than 1 out of 6) experience DLT.
Time frame: 28 days
To estimate the rate of occurrence of acute GvHD
The occurrence of acute GvHD will be recorded for every patient
Time frame: 1 year
To estimate the severity of acute GvHD (according to the MAGIC criteria)
The severity of acute GvHD will be recorded for every patient
Time frame: 1 year
To estimate the rate of occurrence of chronic GvHD
The occurrence of chronic GvHD will be recorded for every patient
Time frame: 1 year
To estimate the severity of chronic GvHD (according to the NIH 2014 criteria)
The severity of chronic GvHD will be recorded for every patient
Time frame: 1 year
To confirm the safety of the approach at the MTD/RD dose
Toxicity of CD19-CAR\_Lenti\_ALLO cells will be recorded for every patient
Time frame: 28 days
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Complete Response (CR) or Complete Response with incomplete blood count recovery (CRi) and MRD negativity achievement.
To evaluate the proportion of patients achieving CR o CR with incomplete blood count recovery (CRi) and MRD negativity by either flow-cytometry or qPCR at day 28 (defined as a value \< 1x10\^-4)
Time frame: 28 days
Probability of CR with MRD negativity achievement according to disease burden at time of enrollment.
To estimate the probability of obtaining CR with MRD negativity stratified according to the disease at time of enrollment (high disease burden being defined as \> 5% bone marrow lymphoblasts, any peripheral blood lymphoblasts, Central Nervous System (CNS) 3 status, or non-CNS Extra-Medullary (EM) site of disease.
Time frame: 28 days
To assess Overll Survival (OS) in the whole populations of patients.
Overall survival of every patient will be evaluated during follow-up
Time frame: 1 year