Safety and Efficacy of SMART101 in Adult Patients With Hematological Malignancies After Haploidentical HSCT With Post-transplant Cyclophosphamide

Phase 1

Recruiting

• Conditions: Hematological Malignancies
• Interventions: Biological: Allogeneic T cell progenitors, cultured ex-vivo

• Registration Number: NCT05768035
• Lead Sponsor: Smart Immune SAS

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-03-02
• Study First Submitted QC: 2023-03-02
• Study First Posted: 2023-03-14
• Study Start: 2023-06-06
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-21
• Last Update Posted: 2023-09-25
• Primary Completion: 2025-07
• Study Completion: 2026-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Patients with acute leukemia or myelodysplastic syndrome and eligible for an haplo PT-Cy HSCT	Allogeneic T cell progenitors, cultured ex-vivo	Segment 1: 3 dose-level SMART101 cells/infusion 1. 1.5 x 106 CD7+ cells per kg of body weight 2. 4.5 x 106 CD7+ cells per kg of body weight 3. 9.0 x 106 CD7+ cells per kg of body weight Segment 2: 2 cohorts of patients will be included in the study based on the type of conditioning regimen: * The cohort A will include up to 17 patients receiving a myeloablative conditioning (MAC). * The cohort B will include up to 17 patients receiving a reduced intensity conditioning (RIC). * Enrollment of patients in each cohort will be done in parallel.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Occurrence of adverse events (AEs)	up to 24 months post-HSCT
Cumulative incidence of infections	Day 100, and Months 6 and 12 post-HSCT
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

Trial Locations

Locations (4)

Centre hospitalier universitaire de Nantes; 🇫🇷 Nantes, France

Institut Paoli Calmettes; 🇫🇷 Marseille, France

Hôpital Saint-Louis; 🇫🇷 Paris, France

CHU Toulouse- Institut Universitaire du cancer Toulouse- Oncopole; 🇫🇷 Toulouse, France