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

Smart Immune

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Hematological Malignancies

Treatments: Biological: Allogeneic T cell progenitors, cultured ex-vivo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04959903

SI101-01

Details and patient eligibility

About

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.

Enrollment: 36 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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36 participants in 2 patient groups

Adult patients affected by hematological malignancies

Experimental group

Description:

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

Treatment:

Biological: Allogeneic T cell progenitors, cultured ex-vivo

Pediatric patients affected by hematological malignancies

Experimental group

Description:

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

Treatment:

Biological: Allogeneic T cell progenitors, cultured ex-vivo