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

NCT05768035 | Recruiting Phase 1 DMC

• 1 other identifier: SI101-02
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 4

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.

Conditions

Hematological Malignancies

Keywords

AML, ALL, MSD

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Occurrence of adverse events (AEs)

  up to 24 months post-HSCT

• T cell immune reconstitution

  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 Outcomes (2)

• Overall Survival (OS)

  Month 24 post-HSCT

• Disease-free Survival

  Month 24 post-HSCT

Study Arms (1)

Patients with acute leukemia or myelodysplastic syndrome and eligible for an haplo PT-Cy HSCT

EXPERIMENTAL

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.

Biological: Allogeneic T cell progenitors, cultured ex-vivo

Interventions

Allogeneic T cell progenitors, cultured ex-vivo BIOLOGICAL

Injection of T cell progenitors 6 days after haplo HSCT and 2 days after the last administration of cyclophosphamide

Also known as: SMART101

Patients with acute leukemia or myelodysplastic syndrome and eligible for an haplo PT-Cy HSCT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Smart Immune SAS: lead

Study Sites (4)

Institut Paoli Calmettes

Marseille, 13009, France

RECRUITING

Centre hospitalier universitaire de Nantes

Nantes, 44093, France

RECRUITING

Hôpital Saint-Louis

Paris, 75010, France

RECRUITING

CHU Toulouse- Institut Universitaire du cancer Toulouse- Oncopole

Toulouse, 31059, France

RECRUITING

MeSH Terms

Conditions

Hematologic Neoplasms; Leukemia, Myeloid, Acute; Multiple Sulfatase Deficiency Disease

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Sulfatidosis; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Officials

• Fabio CICERI, MD, Pr.

  I.R.C.C.S. Ospedale San Raffaele

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Frédéric LEHMANN, MD

CONTACT

+32 (0) 492 46 23 55; frederic.lehmann@smart-immune.com

Aurélie BAUQUET, PhD

CONTACT

aurelie.bauquet@smart-immune.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: * Phase I/II, open-label, dose-escalation, single arm, multicenter study. * This study will comprise two segments: * A phase I dose-escalation segment: Three (3) prespecified dose-levels of SMART101 will be evaluated in three consecutive cohorts of patients whatever the type of conditioning regimen the patients will receive before the HSCT to define the SMART101 recommended dose (RecD). * A phase II segment: once all patients from the dose-escalation segment have completed their "treatment period " and the SMART101 RecD has been defined, a total number of 34 patients will be enrolled at the RecD in the phase II segment of the study.

Study Record Dates

• First Submitted: March 2, 2023
• First Posted: March 14, 2023
• Study Start: June 6, 2023
• Primary Completion: July 1, 2025
• Study Completion (Estimated): July 1, 2026
• Last Updated: September 25, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (4)