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

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