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

• ClinicalTrials.gov Identifier: NCT05768035
• Recruitment Status: Recruiting
• First Posted: March 14, 2023
• Last Update Posted: September 25, 2023
• Sponsor: Smart Immune SAS
• Information provided by (Responsible Party): Smart Immune SAS

Tracking Information

• First Submitted Date: March 2, 2023
• First Posted Date: March 14, 2023
• Last Update Posted Date: September 25, 2023
• Actual Study Start Date: June 6, 2023
• Estimated Primary Completion Date: July 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 21, 2023)

• Occurrence of Unexpected Unacceptable Toxicities (UUT) following the administration of SMART101. [ Time Frame: 14 days post SMART101 infusion ]
  To evaluate the safety of SMART101.
• CD4+ T cell count. [ Time Frame: 100 days post-HSCT ]
  to evaluate the efficacy of the study drug

Original Primary Outcome Measures (submitted: March 2, 2023)

• Occurrence of Unexpected Unacceptable Toxicities (UUT) [ Time Frame: 14 days post SMART101 infusion ]
  to evaluate the safety profile of the study drug
• CD4+ T cell count [ Time Frame: 100 days post-HSCT ]
  to evaluate the efficacy of the study drug

Current Secondary Outcome Measures (submitted: March 2, 2023)

• Occurrence of adverse events (AEs) [ Time Frame: up to 24 months post-HSCT ]
• T cell immune reconstitution [ Time Frame: up to 12 months post-HSCT ]
  Time course of the T cell immune reconstitution, with a focus on naive CD4+ cells and total CD8+cells
• Cumulative incidence of infections [ Time Frame: Day 100, and Months 6 and 12 post-HSCT ]
• Non-relapse mortality (NRM) [ Time Frame: Day 100, and Months 6, 12 and 24 post-HSCT ]

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: March 2, 2023)

• Overall Survival (OS) [ Time Frame: Month 24 post-HSCT ]
• Disease-free Survival [ Time Frame: Month 24 post-HSCT ]

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Safety and Efficacy of SMART101 in Adult Patients With Hematological Malignancies After Haploidentical HSCT With Post-transplant Cyclophosphamide
• Official Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description:

• 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.

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Hematological Malignancies

Intervention

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 Name: SMART101

Study Arms

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. 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.

Intervention: Biological: Allogeneic T cell progenitors, cultured ex-vivo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 21, 2023): 40
• Original Estimated Enrollment (submitted: March 2, 2023): 34
• Estimated Study Completion Date: July 2026
• Estimated Primary Completion Date: July 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Frédéric LEHMANN, MD; +32 (0) 492 46 23 55; frederic.lehmann@smart-immune.com

Contact: Aurélie BAUQUET, PhD; aurelie.bauquet@smart-immune.com

• Listed Location Countries: France

Administrative Information

• NCT Number: NCT05768035
• Other Study ID Numbers: SI101-02
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Smart Immune SAS
• Original Responsible Party: Same as current
• Current Study Sponsor: Smart Immune SAS
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Fabio CICERI, MD, Pr.; I.R.C.C.S. Ospedale San Raffaele

• PRS Account: Smart Immune SAS
• Verification Date: September 2023