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

Phase 1

Recruiting

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

• Registration Number: NCT04959903
• 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 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-07-01
• Study First Submitted QC: 2021-07-12
• Study First Posted: 2021-07-13
• Study Start: 2022-03-31
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-02
• Last Update Posted: 2023-03-06
• Primary Completion: 2025-08
• Study Completion: 2027-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 36

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Pediatric patients affected by hematological malignancies	Allogeneic T cell progenitors, cultured ex-vivo	Pediatric patients affected by acute leukemia (AML, ALL or acute leukemia of ambiguous lineage) eligible for a T depleted allogeneic HSCT
Adult patients affected by hematological malignancies	Allogeneic T cell progenitors, cultured ex-vivo	Adult patients affected by acute leukemia (AML, ALL or acute leukemia of ambiguous lineage) or myelodysplastic syndrome eligible for a T depleted allogeneic HSCT

Primary Outcome Measures

Name	Time	Method
CD4+ T cell count	100 days post-HSCT	to evaluate the efficacy of the study drug
Occurrence of adverse events related to SMART101	100 days post-HSCT	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
Cumulative incidence of grade III-IV GvHD	100 days post-HSCT	to evaluate the safety profile of the study drug

Secondary Outcome Measures

Name	Time	Method
Cumulative incidence of infections	Day 90, and Months 6, 12 and 24 post-HSCT
T cell immune reconstitution	up to Month 12 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 90, and Months 6, 12 and 24 post-HSCT

Trial Locations

Locations (1)

Memorial Sloan Kettering Cancer Center (MSKCC); 🇺🇸 New York, New York, United States