Hematological Malignancies
Conditions
Keywords
AML, ALL, MSD
Brief summary
The purpose of this study is to evaluate the safety and the efficacy of SMART101 (Human T Lymphoid Progenitors (HTLP)) injection to accelerate immune reconstitution after haploidentical hematopoietic stem cell transplantation (HSCT) with post-transplant cyclophosphamide (PT-Cy) in adult patients with hematological malignancies.
Interventions
Injection of T cell progenitors 6 days after haplo HSCT and 2 days after the last administration of cyclophosphamide
Sponsors
Smart Immune SAS
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
* Phase I/II, open-label, dose-escalation, single arm, multicenter study. * This study will comprise two segments: * A phase I dose-escalation segment: Three (3) prespecified dose-levels of SMART101 will be evaluated in three consecutive cohorts of patients whatever the type of conditioning regimen the patients will receive before the HSCT to define the SMART101 recommended dose (RecD). * A phase II segment: once all patients from the dose-escalation segment have completed their treatment period and the SMART101 RecD has been defined, a total number of 34 patients will be enrolled at the RecD in the phase II segment of the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * Patients with AML, ALL or MDS eligible for an allogeneic HSCT with a haploidentical donor with post-transplant cyclophosphamide. * Patients must be ≥ 18 years of age at the time of signing the ICF. * Patients must have a Karnofsky index ≥ 70%. * Patients must have a left ventricular ejection fraction of ≥40%. * Patients must have an intact pulmonary function or Diffusing capacity of the Lungs for Carbon Monoxide (DLCO) ≥ 45% of predicted. * Patients must have adequate hepatic and renal functions, as assessed by standard laboratory criteria. Main
Exclusion criteria
* Patients who have received prior allogeneic stem cell transplantation. * Patients who have received prior treatment with another cellular therapy within 4 weeks before the planned day of SMART101 infusion. * Patients who plan to receive, are concurrently receiving or have received any investigational agent within 4 weeks before the planned day of SMART101 infusion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Unexpected Unacceptable Toxicities (UUT) following the administration of SMART101. | 14 days post SMART101 infusion | To evaluate the safety of SMART101. |
| CD4+ T cell count. | 100 days post-HSCT | to evaluate the efficacy of the study drug |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| T cell immune reconstitution | up to 12 months post-HSCT | Time course of the T cell immune reconstitution, with a focus on naive CD4+ cells and total CD8+cells |
| Non-relapse mortality (NRM) | Day 100, and Months 6, 12 and 24 post-HSCT | — |
| Cumulative incidence of infections | Day 100, and Months 6 and 12 post-HSCT | — |
| Occurrence of adverse events (AEs) | up to 24 months post-HSCT | — |
Other
| Measure | Time frame |
|---|---|
| Overall Survival (OS) | Month 24 post-HSCT |
| Disease-free Survival | Month 24 post-HSCT |
Countries
France
Contacts
Primary ContactFrédéric LEHMANN, MD
Backup ContactAurélie BAUQUET, PhD
Outcome results
None listed