Hematological Malignancies
Conditions
Brief summary
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.
Interventions
Injection of T cell progenitors at \[Day 4-Day 10\] after T cell depleted allogeneic HSCT
Sponsors
Smart Immune SAS
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CD4+ T cell count | 100 days post-HSCT | to evaluate the efficacy of the study drug |
| Occurrence of adverse events related to SMART101 | 100 days post-HSCT | 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 |
| Cumulative incidence of grade III-IV GvHD | 100 days post-HSCT | to evaluate the safety profile of the study drug |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Non-relapse mortality (NRM) | Day 90, and Months 6, 12 and 24 post-HSCT | — |
| T cell immune reconstitution | up to Month 12 post-HSCT | Time course of the T cell immune reconstitution, with a focus on naive CD4+ cells and total CD8+ cells |
| Cumulative incidence of infections | Day 90, and Months 6, 12 and 24 post-HSCT | — |
Other
| Measure | Time frame |
|---|---|
| Overall Survival (OS) | Month 24 post-HSCT |
| Disease-free Survival | Month 24 post-HSCT |
Countries
United States
Contacts
Primary ContactFrédéric LEHMANN, MD
Backup ContactLaura SIMONS, MD, PhD
Outcome results
None listed