A Pilot Clinical Study of OL-101 Injection in Patients with Relapsed or Refractory Multiple Myeloma (RRMM)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 58
- 试验地点
- 3
- 主要终点
- Dose-limiting toxicity (DLT)
研究概览
简要总结
This clinical trial aims to characterize the safety of OL-101 and establish the recommended dose for future research and to evaluate the efficacy of OL-101 (Dose expansion).
详细描述
This study will evaluate the safety and efficacy of OL-101, a chimeric antigen receptor T cell (CAR-T) therapy directed against B-Cell Maturation Antigen (BCMA) and G Protein-Coupled Receptor Class C Group 5 Member D (GPRC5D). This study is a single-arm, open-label, early exploratory clinical trial, conducted in two phases: dose escalation and dose expansion in adults with multiple myeloma. The trial begins with the dose-escalation phase that focus on safety and tolerability, with interval assessments for potential dose escalation or de-escalation. Recommended dose will be selected at the completion of the dose escalation stage in the dose expansion stage. The study aims to assess safety, pharmacokinetic/pharmacodynamic profiles, and efficacy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented diagnosis of multiple myeloma according to the 2014 IMWG diagnostic criteria
- •Relapsed/refractory multiple myeloma as defined by:
- •Received at least 3 prior lines of MM treatment (must include a PI, an IMiD, and an anti-CD38 antibody).
- •2）Disease progression within 12 months of the most recent anti-MM therapy; or disease progression within the past 6 months and subsequently lack response to the most recent line of therapy.
- •Measurable disease at screening as defined by any of the following:
- •Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or
- •Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin free light chain ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio.
- •Positive expression of either BCMA or GPRC5D on bone marrow plasma cells; must be GPRC5D expression positive if previously received BCMA targeted therapy
- •Expected life expectancy exceeds 12 weeks
- •Adequate bone marrow reserve or organ function meeting the following criteria:
- •Hemoglobin ≥ 70 g/L
- •Platelet count ≥ 50 × 10^9/L
- •Absolute lymphocyte count ≥ 0.3×10^9/L
- •Absolute neutrophil count ≥ 1.0 × 10^9/L
- •Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal (ULN)
- •Total bilirubin ≤ 2 times ULN; except in subjects with congenital bilirubinemia (such as Gilbert syndrome, in which case the direct bilirubin ≤1.5 × ULN is required)
- •Creatinine clearance ≥ 60 mL/min (calculated by Cockcroft-Gault equation).
- •corrected serum calcium ≤12.5 mg/dL (≤3.1 mmol/L) or free ionized calcium ≤6.5 mg/dl (≤1.6 mmol/L)
- •SpO2>92% on room air
- •Left ventricular ejection fraction (LVEF) ≥ 50% as assessed by echocardiogram; no clinically meaningful pericardial effusion by ultrasound
排除标准
- •Solitary plasmacytoma
- •Known active central nervous system (CNS) involvement or exhibits clinical signs of CNS involvement of multiple myeloma.
- •Received allogeneic stem cell transplant; received autologous stem cell transplant within 12 weeks before screening
- •Active second primary malignant tumor, exclude the following: cured non- melanoma skin cancer, non-metastatic prostate cancer, cervical carcinoma in situ, ductal or lobular carcinoma in situ of the breast
- •Any other significant medical disease, abnormality, or condition that, in the investigator judgment, may make the patient unsuitable for participation in the study or put the patient at risk.
- •Plasma cell leukemia, Waldenström's macroglobulinemia, POEMS syndrome, or primary AL amyloidosis.
研究组 & 干预措施
OL-101 infusion
This arm provides CAR-T treatment at the dose the patient is assigned to.
干预措施: OL-101 infusion (Biological)
结局指标
主要结局
Dose-limiting toxicity (DLT)
时间窗: Within 28 days post CAR-T infusion
Adverse events will be assessed based on the CTCAE 5.0
Treatment emergent adverse event (TEAE) incidence and severity
时间窗: From aphresis till 1 year after CAR-T infusion or start of a new anti-cancer therapy, whichever is earlier
Adverse events will be assessed based on the CTCAE 5.0
次要结局
- Level of Immunogenicity(Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first)
- Level of RCL(Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first)
- Overall response rate (ORR)(Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first)
- Minimal residual disease (MRD) negative rate(Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first)
- Duration of response (DOR)(Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first)
- Progression-free survival (PFS)(Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first)
- Overall survival (OS)(Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first)
- Cmax of OL-101(Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first)
- Tmax of OL-101(Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first)
- AUC 0-28days of OL-101(Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first)
- Serum cytokines(Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first)
- Serum soluble circulating BCMA (sBCMA)(Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first)
研究者
He Huang
Professor
Zhejiang University