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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hematological Malignancies

Intervention / Treatment
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* Biological: Allogeneic T cell progenitors, cultured ex-vivo


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adult patients affected by hematological malignancies<br>Adult patients affected by acute leukemia (AML, ALL or acute leukemia of ambiguous lineage) or myelodysplastic syndrome eligible for a T depleted allogeneic HSCT | Biological: Allogeneic T cell progenitors, cultured ex-vivo<br>* Injection of T cell progenitors at [Day 4-Day 10] after T cell depleted allogeneic HSCT<br>* Other names: SMART101;|
| Experimental: Pediatric patients affected by hematological malignancies<br>Pediatric patients affected by acute leukemia (AML, ALL or acute leukemia of ambiguous lineage) eligible for a T depleted allogeneic HSCT | Biological: Allogeneic T cell progenitors, cultured ex-vivo<br>* Injection of T cell progenitors at [Day 4-Day 10] after T cell depleted allogeneic HSCT<br>* Other names: SMART101;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative incidence of grade III-IV GvHD | to evaluate the safety profile of the study drug | 100 days post-HSCT | 
| Occurrence of adverse events related to SMART101 | 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 | 100 days post-HSCT | 
| CD4+ T cell count | to evaluate the efficacy of the study drug | 100 days post-HSCT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| T cell immune reconstitution | Time course of the T cell immune reconstitution, with a focus on naive CD4+ cells and total CD8+ cells | up to Month 12 post-HSCT | 
| Cumulative incidence of infections |  | Day 90, and Months 6, 12 and 24 post-HSCT | 
| Non-relapse mortality (NRM) |  | Day 90, and Months 6, 12 and 24 post-HSCT |