2024-517953-28-00招募中2 期
An open-label, randomized, non-comparative multi-center phase I/II study to assess the safety and the efficacy of SMART101 after HLA-mismatched peripheral blood stem cell transplantation with post-transplant cyclophosphamide in patients with hematological malignancies
Smart Immune, Smart Immune7 个研究点 分布在 2 个国家目标入组 39 人开始时间: 2024年11月29日最近更新:
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 39
- 试验地点
- 7
- 主要终点
- Safety (Segment 1 and Segment 2): Occurrence of Unexpected Unacceptable Toxicities (UUT) following the administration of SMART101, within 28 days post SMART101 infusion
研究概览
简要总结
Segment 1: To determine the SMART101 recommended dose (RecD)
Segment 2:
- Safety: To evaluate the safety of SMART101 in term of unacceptable toxicity in the SMART101 arm
- Efficacy: To evaluate the activity of SMART101 in term of CD4+ T-cell reconstitution
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •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.
- •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.
- •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 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
- •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
- •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
排除标准
- •Patients who have received prior allogeneic stem cell transplantation
- •Any abnormal condition or laboratory result that may alter patient’s condition or study outcome according to the Investigator’s judgement
- •Patients with a history of allergic reactions or hypersensitivity attributed to the excipients of SMART101 (dimethyl sulfoxide [DMSO])
- •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
- •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
- •Patients who have uncontrolled infection
- •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
- •Patients with a documented Hepatitis B or hepatitis C infection with measurable viral load
- •Patients with a known liver cirrhosis
- •Patients with a confirmed tumor involvement in the central nervous system (CNS)
- •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)
结局指标
主要结局
Safety (Segment 1 and Segment 2): Occurrence of Unexpected Unacceptable Toxicities (UUT) following the administration of SMART101, within 28 days post SMART101 infusion
Safety (Segment 1 and Segment 2): Occurrence of Unexpected Unacceptable Toxicities (UUT) following the administration of SMART101, within 28 days post SMART101 infusion
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
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
次要结局
- 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
- 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
- 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
- NK cell reconstitution at D30, D60, D100, M4, M5, M6, M9 and M12
- Analysis of the recent thymic emigrant (RTE) at D30, D60, D100, M4, M5, M6, M9 and M12
- Analysis of T-cell receptor excision circle (TREC) at baseline (before conditioning), D60, D100, M4, M5, M6,M9 and M12
- Imaging of the thymus with 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
- 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)
研究者
Clinical Development Department
Scientific
Smart Immune
研究点 (7)
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