Safety and Efficacy of SMART101 in Pediatric and Adult Patients With Hematological Malignancies After T Cell Depleted Allo-HSCT

A Phase I/II Study Evaluating the Safety and the Efficacy of SMART101 Injection to Accelerate Immune Reconstitution After T Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric and Adult Patients With Hematological Malignancies

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Phase 2; Phase 1

Contacts and Locations

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

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center (MSKCC)
      • Sub-Investigator: Miguel-Angel PERALES, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adult patients affected by hematological malignancies; Adult patients affected by acute leukemia (AML, ALL or acute leukemia of ambiguous lineage) or myelodysplastic syndrome eligible for a T depleted allogeneic HSCT	Biological: Allogeneic T cell progenitors, cultured ex-vivo; Injection of T cell progenitors at [Day 4-Day 10] after T cell depleted allogeneic HSCT; Other Names: SMART101
Experimental: Pediatric patients affected by hematological malignancies; Pediatric patients affected by acute leukemia (AML, ALL or acute leukemia of ambiguous lineage) eligible for a T depleted allogeneic HSCT	Biological: Allogeneic T cell progenitors, cultured ex-vivo; Injection of T cell progenitors at [Day 4-Day 10] after T cell depleted allogeneic HSCT; Other Names: SMART101

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of grade III-IV GvHD	to evaluate the safety profile of the study drug	100 days post-HSCT
Occurrence of adverse events related to SMART101	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	100 days post-HSCT
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
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 Month 12 post-HSCT
Cumulative incidence of infections		Day 90, and Months 6, 12 and 24 post-HSCT
Non-relapse mortality (NRM)		Day 90, 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: Jaap-Jan BOELENS, MD, PhD, Memorial Sloan Kettering Cancer Center (MSKCC)

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2022
• Primary Completion (Anticipated): August 1, 2025
• Study Completion (Anticipated): May 1, 2027

Study Registration Dates

• First Submitted: July 1, 2021
• First Submitted That Met QC Criteria: July 12, 2021
• First Posted (Actual): July 13, 2021

Study Record Updates

• Last Update Posted (Estimate): March 6, 2023
• Last Update Submitted That Met QC Criteria: March 2, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms
• Other Study ID Numbers: SI101-01

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: Yes
• Studies a U.S. FDA-regulated device product: No