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