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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Hematological Malignancies
• Intervention / Treatment: Biological: Allogeneic T cell progenitors, cultured ex-vivo

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Frédéric LEHMANN, MD; Phone Number: +32 (0) 492 46 23 55; Email: frederic.lehmann@smart-immune.com
• Study Contact Backup: Name: Aurélie BAUQUET, PhD; Email: aurelie.bauquet@smart-immune.com

Study Locations

• France
  • Marseille, France, 13009
    • Recruiting
    • Institut Paoli Calmettes
    • Principal Investigator: Raynier Devillier, Pr
  • Nantes, France, 44093
    • Recruiting
    • Centre Hospitalier Universitaire de Nantes
    • Principal Investigator: Patrice Chevallier, MD, PhD
  • Paris, France, 75010
    • Recruiting
    • Hopital Saint-Louis
    • Principal Investigator: Régis Peffault de Latour, Pr
  • Toulouse, France, 31059
    • Recruiting
    • CHU Toulouse- Institut Universitaire du cancer Toulouse- Oncopole
    • Principal Investigator: Anne HUYNH, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Patients with acute leukemia or myelodysplastic syndrome and eligible for an haplo PT-Cy HSCT; Segment 1: 3 dose-level SMART101 cells/infusion; 1.5 x 106 CD7+ cells per kg of body weight; 4.5 x 106 CD7+ cells per kg of body weight; 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.

Biological: Allogeneic T cell progenitors, cultured ex-vivo; Injection of T cell progenitors 6 days after haplo HSCT and 2 days after the last administration of cyclophosphamide; Other Names: SMART101

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Unexpected Unacceptable Toxicities (UUT) following the administration of SMART101.	To evaluate the safety of SMART101.	14 days post SMART101 infusion
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
Occurrence of adverse events (AEs)		up to 24 months post-HSCT
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 12 months post-HSCT
Cumulative incidence of infections		Day 100, and Months 6 and 12 post-HSCT
Non-relapse mortality (NRM)		Day 100, and Months 6, 12 and 24 post-HSCT

Other Outcome Measures

Outcome Measure	Time Frame
Overall Survival (OS)	Month 24 post-HSCT
Disease-free Survival	Month 24 post-HSCT

Collaborators and Investigators

• Sponsor: Smart Immune SAS
• Investigators: Principal Investigator: Fabio CICERI, MD, Pr., I.R.C.C.S. Ospedale San Raffaele

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2023
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: March 2, 2023
• First Submitted That Met QC Criteria: March 2, 2023
• First Posted (Actual): March 14, 2023

Study Record Updates

• Last Update Posted (Actual): September 25, 2023
• Last Update Submitted That Met QC Criteria: September 21, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: AML, ALL, MSD
• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms
• Other Study ID Numbers: SI101-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No