Safety and Efficacy of SMART101 in Pediatric and Adult Patients With Hematological Malignancies After T Cell Depleted Allo-HSCT

Safety and Efficacy of SMART101 in Pediatric and Adult Patients With Hematological Malignancies After T Cell Depleted Allo-HSCT

A Phase I/II Study Evaluating the Safety and the Efficacy of SMART101 Injection to Accelerate Immune Reconstitution After T Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric and Adult Patients With Hematological Malignancies

The purpose of this study is to evaluate the safety and the efficacy of SMART101 (Human T Lymphoid Progenitor (HTLP)) injection to accelerate immune reconstitution after T cell depleted allogeneic hematopoietic stem cell transplantation (HSCT) in adult and pediatric patients with hematological malignancies.

Adult patients affected by acute leukemia (AML, ALL or acute leukemia of ambiguous lineage) or myelodysplastic syndrome eligible for a T depleted allogeneic HSCT

Pediatric patients affected by acute leukemia (AML, ALL or acute leukemia of ambiguous lineage) eligible for a T depleted allogeneic HSCT

Number of adverse events and serious adverse events related to SMART101 tabulated for each dose and by age group to evaluate the safety profile of the study drug

Time course of the T cell immune reconstitution, with a focus on naive CD4+ cells and total CD8+ cells

Inclusion Criteria: Group A (adults): Adult patients affected by: Acute leukemia (AML, ALL) defined as: Acute Myeloid Leukemia (AML): High risk AML in CR1; any adverse genetic abnormality, secondary or therapy related AML excluding good risk genetic abnormalities Chemo-refractory relapse (MRD+) ≥ CR2 Acute Lymphoblastic Leukemia (ALL): Chemo-refractory relapse (MRD+) High risk ALL in CR1; Philadelphia (like) or any poor risk feature ≥ CR2 Acute leukemia of ambiguous lineage: ≥ CR1 with a minimal residual disease (MRD) <5% (flow cytometry, molecular and/or cytogenetics accepted) Myelodysplastic Syndrome (MDS) with least one of the following: Revised International Prognostic Scoring System risk score of intermediate or higher at the time of transplant evaluation. Life-threatening cytopenia. Karyotype or genomic changes that indicate high risk for progression to acute myelogenous leukemia, including abnormalities of chromosome 7 or 3, mutations of TP53, or complex or monosomal karyotype. Therapy related disease or disease evolving from other malignant processes. Patient eligible for a T-depleted allogeneic HSCT Age ≥ 18y and clinical condition compatible with allogeneic stem cell transplantation Karnofsky index ≥ 70% prior to conditioning regimen Patients with normal organ function prior to conditioning regimen Group B (pediatrics): Pediatric patients affected by acute leukemia defined as: Acute Myeloid Leukemia (AML): High risk AML in CR1; any adverse genetic abnormality, secondary or therapy related AML excluding good risk genetic abnormalities, Chemo-refractory relapse (MRD+) ≥ CR2 Acute Lymphoblastic Leukemia (ALL): Chemo-refractory relapse (MRD+) High risk ALL in CR1; Philadelphia (like) or any poor risk feature ≥ CR2 Acute leukemia of ambiguous lineage: ≥ CR1 with a minimal residual disease (MRD) <5% (flow cytometry, molecular and/or cytogenetics accepted) Patient eligible for a T-depleted allogeneic HSCT Age < 18y at the time of inclusion Absence of a matched sibling donor (MSD) Lansky ≥ 70% / Karnofsky performance status ≥ 70% prior to conditioning regimen Patients with normal organ function prior to conditioning regimen Exclusion Criteria: Groups A and B: Use of an HLA matched Cord Blood (8/8 allele matched) or haploidentical donor Prior therapy with allogeneic stem cell transplantation Treatment with another cellular therapy within one month before inclusion