Back to resultsSafety and Efficacy of SMART101 in Adult Patients With Hematological Malignancies After Haploidentical HSCT With Post-transplant Cyclophosphamide
Primary Purpose
Hematological Malignancies
Status
Recruiting
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
Allogeneic T cell progenitors, cultured ex-vivo
Sponsored by
About this trial
This is an interventional treatment trial for Hematological Malignancies focused on measuring AML, ALL, MSD
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.
Sites / Locations
- Institut Paoli CalmettesRecruiting
- Centre hospitalier universitaire de NantesRecruiting
- Hôpital Saint-LouisRecruiting
- CHU Toulouse- Institut Universitaire du cancer Toulouse- OncopoleRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Patients with acute leukemia or myelodysplastic syndrome and eligible for an haplo PT-Cy HSCT
Arm Description
Segment 1: 3 dose-level SMART101 cells/infusion 1.5 x 106 CD7+ cells per kg of body weight 4.5 x 106 CD7+ cells per kg of body weight 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.
Outcomes
Primary Outcome Measures
Occurrence of Unexpected Unacceptable Toxicities (UUT) following the administration of SMART101.
To evaluate the safety of SMART101.
CD4+ T cell count.
to evaluate the efficacy of the study drug
Secondary Outcome Measures
Occurrence of adverse events (AEs)
T cell immune reconstitution
Time course of the T cell immune reconstitution, with a focus on naive CD4+ cells and total CD8+cells
Cumulative incidence of infections
Non-relapse mortality (NRM)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05768035
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 6, 2023 (Actual)
Primary Completion Date
July 2025 (Anticipated)
Study Completion Date
July 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Smart Immune SAS
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematological Malignancies
Keywords
AML, ALL, MSD
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
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)
Allocation
N/A
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Patients with acute leukemia or myelodysplastic syndrome and eligible for an haplo PT-Cy HSCT
Arm Type
Experimental
Arm Description
Segment 1: 3 dose-level SMART101 cells/infusion
1.5 x 106 CD7+ cells per kg of body weight
4.5 x 106 CD7+ cells per kg of body weight
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 Type
Biological
Intervention Name(s)
Allogeneic T cell progenitors, cultured ex-vivo
Other Intervention Name(s)
SMART101
Intervention Description
Injection of T cell progenitors 6 days after haplo HSCT and 2 days after the last administration of cyclophosphamide
Primary Outcome Measure Information:
Title
Occurrence of Unexpected Unacceptable Toxicities (UUT) following the administration of SMART101.
Description
To evaluate the safety of SMART101.
Time Frame
14 days post SMART101 infusion
Title
CD4+ T cell count.
Description
to evaluate the efficacy of the study drug
Time Frame
100 days post-HSCT
Secondary Outcome Measure Information:
Title
Occurrence of adverse events (AEs)
Time Frame
up to 24 months post-HSCT
Title
T cell immune reconstitution
Description
Time course of the T cell immune reconstitution, with a focus on naive CD4+ cells and total CD8+cells
Time Frame
up to 12 months post-HSCT
Title
Cumulative incidence of infections
Time Frame
Day 100, and Months 6 and 12 post-HSCT
Title
Non-relapse mortality (NRM)
Time Frame
Day 100, and Months 6, 12 and 24 post-HSCT
Other Pre-specified Outcome Measures:
Title
Overall Survival (OS)
Time Frame
Month 24 post-HSCT
Title
Disease-free Survival
Time Frame
Month 24 post-HSCT
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Frédéric LEHMANN, MD
Phone
+32 (0) 492 46 23 55
Email
frederic.lehmann@smart-immune.com
First Name & Middle Initial & Last Name or Official Title & Degree
Aurélie BAUQUET, PhD
Email
aurelie.bauquet@smart-immune.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fabio CICERI, MD, Pr.
Organizational Affiliation
I.R.C.C.S. Ospedale San Raffaele
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institut Paoli Calmettes
City
Marseille
ZIP/Postal Code
13009
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Raynier Devillier, Pr
Facility Name
Centre hospitalier universitaire de Nantes
City
Nantes
ZIP/Postal Code
44093
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Patrice Chevallier, MD, PhD
Facility Name
Hôpital Saint-Louis
City
Paris
ZIP/Postal Code
75010
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Régis Peffault de Latour, Pr
Facility Name
CHU Toulouse- Institut Universitaire du cancer Toulouse- Oncopole
City
Toulouse
ZIP/Postal Code
31059
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anne Huynh, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Safety and Efficacy of SMART101 in Adult Patients With Hematological Malignancies After Haploidentical HSCT With Post-transplant Cyclophosphamide
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