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

Inclusion Criteria

Group A (adults):

1. 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.

2. Patient eligible for a T-depleted allogeneic HSCT

3. Age ≥ 18y and clinical condition compatible with allogeneic stem cell transplantation

4. Karnofsky index ≥ 70% prior to conditioning regimen

5. Patients with normal organ function prior to conditioning regimen

Group B (pediatrics):

1. 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)

2. Patient eligible for a T-depleted allogeneic HSCT

3. Age < 18y at the time of inclusion

4. Absence of a matched sibling donor (MSD)

5. Lansky ≥ 70% / Karnofsky performance status ≥ 70% prior to conditioning regimen

6. Patients with normal organ function prior to conditioning regimen

Exclusion Criteria

Groups A and B:

1. Use of an HLA matched Cord Blood (8/8 allele matched) or haploidentical donor
2. Prior therapy with allogeneic stem cell transplantation
3. Treatment with another cellular therapy within one month before inclusion