ALLOGENEIC T-CELL PRECURSORS, MOBILIZED PERIPHERAL BLOOD-DERIVED, EX VIVO CULTURED for Acute myeloid leukaemia|Acute lymphoblastic leukaemia|Myelodysplastic syndromes|Hematological malignancy

Inclusion criteria

• {"criterion_text":"- Patients and Donors written informed consents. Patients must have voluntarily signed the written informed consent (ICF) before performance of any study-related inclusion procedures. Donors must have voluntarily signed the written ICF before the apheresis donation.\n- Patients with AML, ALL or MDS eligible for an allogeneic HSCT with a HLA-mismatched donor (haploidentical or 9/10 matched unrelated donor, MUD) with post-transplant cyclophosphamide. In case of ≥ 5% bone marrow blasts, the investigator must contact the Sponsor for review and final eligibility decision.\n- Patients must be ≥ 18 years of age at the time of signing the ICF\n- Patients must have a Karnofsky index ≥ 70%\n- Patients must have a left ventricular ejection fraction of ≥40%\n- Patients must have an intact pulmonary function or Diffusing capacity of the Lungs for Carbon Monoxide (DLCO) ≥ 45% of predicted\n- Patients must have adequate hepatic and renal functions, as assessed by standard laboratory criteria and defined as: Bilirubin ≤ 1.5 x upper limit of normal (ULN) or ≤ 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert’s Syndrome, hemolysis or transfusion dependence; AST and ALT ≤ 2.5 x ULN; Alkaline phosphatase < 5 x ULN; Serum creatinine < 1.5 × ULN or creatinine clearance ≥ 60 mL/min (Cockcroft and Gault) for serum creatinine ≥ 1.5x ULN\n- Women of childbearing potential must: have a negative pregnancy test; sexually active women must agree to use an effective method of birth control with their male partner (combined hormonal contraception or progesterone-only hormonal contraception associated with inhibition of ovulation, intrauterine device (IUD) intrauterine hormone-releasing system (IUS) bilateral tubal occlusion, vasectomy or sexual abstinence) consistently and correctly for at least 1 year after the last administration of cyclophosphamide; agree to not donate eggs (ova, oocytes) for the purposes of assisted reproduction for at least 1 year after the last administration of cyclophosphamide; agree to no plan to breastfeed for at least 100 days after the infusion of SMART101 and no plan to become pregnant for at least 1 year after the last administration of cyclophosphamide\n- Males who are sexually active must: agree to use an effective method of birth control with their partner of childbearing potential (combined hormonal contraception or progesterone-only hormonal contraception associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system (IUS) bilateral tubal occlusion, vasectomy or sexual abstinence) consistently and correctly for at least 6 months after the last administration of cyclophosphamide or 1 year after the last administration of Thiotepa if applicable; agree to not donate sperm for at least 6 months after the last administration of cyclophosphamide or 1 year after the last administration of Thiotepa if applicable; no plan to father a child within 6 months after the last administration of cyclophosphamide or 1 year after the last administration of Thiotepa if applicable"}

Exclusion criteria

• {"criterion_text":"- Patients who have received prior allogeneic stem cell transplantation\n- Any abnormal condition or laboratory result that may alter patient’s condition or study outcome according to the Investigator’s judgement\n- Patients with a history of allergic reactions or hypersensitivity attributed to the excipients of SMART101 (dimethyl sulfoxide [DMSO])\n- Patients with a contraindication, including allergic reactions or hypersensitivity, to any medication as proposed per protocol or used as standard of care according to institutional standards of each participating stud site during the whole study\n- Patients who have received prior treatment with another cellular therapy within 4 weeks before the planned day of SMART101 infusion\n- Patients who plan to receive, are concurrently receiving or have received any investigational agent within 4 weeks before the planned day of SMART101 infusion\n- Patients who have uncontrolled infection\n- Patients with a documented history of human immunodeficiency virus (HIV) or human T-cell leukemia virus type 1 (HTLV-1), diagnosed by antibody assays or found positive following the serology testing scheduled at screening\n- Patients with a documented Hepatitis B or hepatitis C infection with measurable viral load\n- Patients with a known liver cirrhosis\n- Patients with a confirmed tumor involvement in the central nervous system (CNS)\n- Patients with psychiatric/social situations or addictive disorders, including active alcohol, that may compromise the ability of the patients to give informed consent or to comply with the study procedures (according to the Investigator’s judgement)"}

Primary endpoints

• {"endpoint_text":"- Safety (Segment 1 and Segment 2): Occurrence of Unexpected Unacceptable Toxicities (UUT) following the administration of SMART101, within 28 days post SMART101 infusion","definition_or_measurement_approach":"Occurrence of Unexpected Unacceptable Toxicities (UUT) following the administration of SMART101 within 28 days post SMART101 infusion (time window: 28 days post infusion)"}
• {"endpoint_text":"- Efficacy (Segment 2): T-cell reconstitution rate, defined as naïve CD4+ T cell count ≥ 50/μL within 100 days post-HSCT, confirmed on a subsequent measurement within 2 months","definition_or_measurement_approach":"Defined as naïve CD4+ T cell count ≥ 50/μL within 100 days post-HSCT, with confirmation on a subsequent measurement within 2 months"}

Secondary endpoints

• {"endpoint_text":"- Occurrence of all adverse events (AEs) and serious adverse events (SAEs), and specifically the occurrence of Adverse Event of Special Interest (AESI) related to the HSCT procedure following the administration of SMART101, defined as: Grade III-IV acute GvHD; Graft failure","definition_or_measurement_approach":"Recording and grading of AEs/SAEs; AESIs defined as Grade III-IV acute GvHD and graft failure"}
• {"endpoint_text":"- T-cell reconstitution defined as the assessment of the different CD3+ TCRαβ+ cell subpopulations at D30, D60, D100, M4, M5, M6, M9 and M12: Naïve CD4+ and CD8+ populations; Memory T cells within the CD4 and CD8 T cell compartments; Activated T cells within the CD4 and CD8 T cell compartments; Regulatory T cells","definition_or_measurement_approach":"Flow cytometry assessment of CD3+ TCRαβ+ subpopulations at specified timepoints (D30, D60, D100, M4, M5, M6, M9, M12)"}
• {"endpoint_text":"- B-cell reconstitution defined as the following parameters at D30, D60, D100, M4, M5, M6, M9 and M12: Number of B cells; Ig levels; Stop of intravenously IgG replacement therapy","definition_or_measurement_approach":"Quantification of B-cell counts, immunoglobulin levels and documentation of cessation of IVIG replacement at specified timepoints"}
• {"endpoint_text":"- NK cell reconstitution at D30, D60, D100, M4, M5, M6, M9 and M12","definition_or_measurement_approach":"Assessment of NK cell counts at specified timepoints"}
• {"endpoint_text":"- Analysis of the recent thymic emigrant (RTE) at D30, D60, D100, M4, M5, M6, M9 and M12","definition_or_measurement_approach":"Measurement of RTE populations at specified timepoints"}
• {"endpoint_text":"- Analysis of T-cell receptor excision circle (TREC) at baseline (before conditioning), D60, D100, M4, M5, M6,M9 and M12","definition_or_measurement_approach":"Quantification of TREC at baseline and specified post-transplant timepoints"}
• {"endpoint_text":"- Imaging of the thymus with MRI at baseline (before conditioning) and M6","definition_or_measurement_approach":"MRI imaging of thymus at baseline and month 6"}
• {"endpoint_text":"- Cumulative incidence of infections at D100, M6 and M12","definition_or_measurement_approach":"Calculation of cumulative incidence of infections at the specified timepoints"}
• {"endpoint_text":"- NRM cumulative incidence at D100, M6, M12 and M24","definition_or_measurement_approach":"Calculation of non-relapse mortality cumulative incidence at specified timepoints"}
• {"endpoint_text":"- The following endpoints at D100, M6, M12 and M24: Relapse rate (RR); Event free survival (EFS); Disease-free survival (DFS); GvHD-free, relapse-free survival (GRFS); Overall survival (OS)","definition_or_measurement_approach":"Standard survival analyses and event rate calculations at specified timepoints (D100, M6, M12, M24)"}

France

Latest Decision Or Authorization Date

03-04-2025

Number Of Sites

5

Number Of Participants

26

Italy

Latest Decision Or Authorization Date

03-12-2024

Number Of Sites

2

Number Of Participants

13

Primary sponsor

Full Name

Smart Immune

Organisation Type

Pharmaceutical company

Country Of Registered Address

France