Patients with hematological malignancies requiring haploidentical peripheral blood stem transplantation with post-transplant cyclophosphamide MedDRA version: 21.1 Level: LLT Classification code 10066481 Term: Hematological malignancy System Organ Class: 100000004864
Conditions
Interventions
Product Name: Allogeneic human T lymphoid progenitor cells
Product Code: SMART101
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: na
Current Sponsor code: SMART101
Other descriptive
Sponsors
SMART IMMUNE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients must have voluntarily signed the written informed consent (ICF) before performance of any study-related inclusion procedures. 2. Patients with AML, ALL or MDS eligible for an allogeneic HSCT with a haploidentical donor with post-transplant cyclophosphamide. In case of = 5% bone marrow blasts, the investigator must contact the Sponsor for review and final eligibility decision. Note: The eligibility to the standard of care haploidentical HSCT with PT-Cy will be based on each participating institution guidelines. 3. Patients must be = 18 years of age at the time of signing the ICF. 4. Patients must have a Karnofsky index = 70%. 5. Patients must have a left ventricular ejection fraction of =40%. 6. Patients must have an intact pulmonary function or Diffusing capacity of the Lungs for Carbon Monoxide (DLCO) = 45% of predicted. 7. 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) unless felt to be related to Gilbert’s disease or hemolysis, • Aspartate transaminase (AST) and alanine transaminase (ALT) = 2.5 x ULN, • Alkaline phosphatase =65 years) yes F.1.3.1 Number of subjects for this age range 12
Exclusion criteria
Exclusion criteria: 1. Patients who have received prior allogeneic stem cell transplantation. 2. Patients who have received prior treatment with another cellular therapy within 4 weeks before the planned day of SMART101 infusion. 3. Patients who plan to receive, are concurrently receiving or have received any investigational agent within 4 weeks before the planned day of SMART101 infusion. 4. Patients who have uncontrolled infection. 5. 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. 6. Patients with a documented Hepatitis B or hepatitis C infection with measurable viral load. 7. Patients with a known liver cirrhosis. 8. Patients with a confirmed tumor involvement in the central nervous system (CNS). 9. 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). 10. Any abnormal condition or laboratory result that may alter patient’s condition or study outcome according to the Investigator’s judgement.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Safety: To evaluate the safety of SMART101 in term of unacceptable toxicity • Efficacy: To evaluate the activity of SMART101 in term of CD4+ T-cell reconstitution;Secondary Objective: • To assess the safety profile of SMART101 • To determine the efficacy of SMART101 in improving immune reconstitution post-HSCT • To assess the efficacy of SMART101 in improving thymus function post-HSCT • To assess the efficacy of SMART101 in preventing infections post-HSCT • To assess the efficacy of SMART101 in reducing non-relapse mortality (NRM) post-HSCT • To assess the efficacy of SMART101 in improving long-term outcomes post-HSCT;Primary end point(s): • Safety: Occurrence of Unexpected Unacceptable Toxicities (UUT) following the administration of SMART101, within 14 days post SMART101 infusion and defined as: - Any CTCAE Grade 5 not due to the underlying malignancy, - Any CTCAE Grade 3 or higher allergic reactions related to SMART101 infusion that cannot be controlled to a Grade 1 or less within 24 hours of treatment with appropriate treatment, - Any CTCAE Grade 3 or higher non-hematological toxicity related to SMART101 infusion that could lead to irreversible damage of a vital organ and that cannot be controlled to Grade 1 or less within 7 days with appropriate treatment. • Efficacy: 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. ;Timepoint(s) of evaluation of this end point: As defined in each co-primary endpoint | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • 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: o Grade III-IV acute graft-versus-host disease (GvHD), o Graft failure. • T-cell reconstitution defined as the assessment of the different CD3+ TCRaß+ cell subpopulations at D30, D60, D100, M6 and M12: o Naïve CD4+ and CD8+ populations, o Memory T cells within the CD4 and CD8 T cell compartments (central memory, effector memory, stem memory and effector memory re-expressing CD45RA (EMRA) cells), o Activated T cells within the CD4 and CD8 T cell compartments, o Regulatory T cells. • B-cell reconstitution defined as the following parameters at D30, D60, D100, M6 and M12: o Number of B cells, o Ig levels, o Stop of intravenously IgG replacement therapy. • Natural Killer (NK) cell reconstitution at D30, D60, D100, M6 and M12. • Analysis of the recent thymic emigrant (RTE) at D30, D60, D100, M6 and M12. • Analysis of T-cell receptor excision circle (TREC) at baseline (before conditioning), D60, D100, M6 and M12. • Imaging of the thymus with magnetic resonance imaging (MRI) at baseline (before conditioning) and M6. • Cumulative incidence of infections at D100, M6 and M12. • NRM cumulative incidence at D100, M6, M12 and M24. • Relapse rate (RR) at D100, M6, M12 and M24. • Event free survival (EFS) at D100, M6, M12 and M24. • Disease-free survival (DFS) at D100, M6, M12 and M24. • GvHD-free, relapse-free survival (GRFS) at D100, M6, M12 and M24. • Overall survival (OS) at D100, M6, M12 and M24. ;Timepoint(s) of evaluation of this end point: As defined in each secondary endpoint | — |
Countries
France, Italy, United States
Contacts
Public ContactRegulatory Affairs
SMART IMMUNE
Outcome results
None listed