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

Hematological Malignancies Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04959903
• Other study ID #: SI101-01
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 31, 2022
• Est. completion date: May 2027

Study information

• Verified date: March 2023
• Source: Smart Immune SAS
• Contact: Frédéric LEHMANN, MD
• Phone: +32 (0) 492 46 23 55
• Email: frederic.lehmann[@]smart-immune.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: May 2027
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Hematological Malignancies
• Neoplasms

Intervention

Biological:
• Allogeneic T cell progenitors, cultured ex-vivo
Injection of T cell progenitors at [Day 4-Day 10] after T cell depleted allogeneic HSCT

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Cancer Center (MSKCC)	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Smart Immune SAS

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overall Survival (OS)		Month 24 post-HSCT
Other	Disease-free Survival		Month 24 post-HSCT
Primary	Cumulative incidence of grade III-IV GvHD	to evaluate the safety profile of the study drug	100 days post-HSCT
Primary	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
Primary	CD4+ T cell count	to evaluate the efficacy of the study drug	100 days post-HSCT
Secondary	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
Secondary	Cumulative incidence of infections		Day 90, and Months 6, 12 and 24 post-HSCT
Secondary	Non-relapse mortality (NRM)		Day 90, and Months 6, 12 and 24 post-HSCT