Clinical trial NCT05768035: Safety and Efficacy of SMART101 in Adult Patients With Hematological Malignancies After Haploidentical HSCT With Post-transplant Cyclophosphamide
Official title: An Open-label, Multi-center Phase I/II Study to Assess the Safety and the Efficacy of SMART101 After Haploidentical Peripheral Blood Stem Transplantation With Post-transplant Cyclophosphamide in Subjects With Hematological Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Hematological Malignancies
Keywords: AML, ALL, MSD
Lead sponsor: Smart Immune SAS
Sponsor class: INDUSTRY
First posted: 2023-03-14
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Occurrence of Unexpected Unacceptable Toxicities (UUT) following the administration of SMART101.
timeFrame: 14 days post SMART101 infusion
measure: CD4+ T cell count.
timeFrame: 100 days post-HSCT
Secondary outcomes:
measure: Occurrence of adverse events (AEs)
timeFrame: up to 24 months post-HSCT
measure: T cell immune reconstitution
timeFrame: up to 12 months post-HSCT
measure: Cumulative incidence of infections
timeFrame: Day 100, and Months 6 and 12 post-HSCT
measure: Non-relapse mortality (NRM)
timeFrame: Day 100, and Months 6, 12 and 24 post-HSCT
Other outcomes:
measure: Overall Survival (OS)
timeFrame: Month 24 post-HSCT
measure: Disease-free Survival
timeFrame: Month 24 post-HSCT
Locations:
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Nantes
country: France
facility: Centre hospitalier universitaire de Nantes
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Toulouse
country: France
facility: CHU Toulouse- Institut Universitaire du cancer Toulouse- Oncopole
Study officials:
affiliation: I.R.C.C.S. Ospedale San Raffaele
name: Fabio CICERI, MD, Pr.
role: PRINCIPAL_INVESTIGATOR
References: