A Study of OL-101 Injection in Patients with Relapsed or Refractory Multiple Myeloma (RRMM)

Официальное название

A Pilot Clinical Study of OL-101 Injection in Patients with Relapsed or Refractory Multiple Myeloma (RRMM)

Обзор

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).

Подробное описание

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.

Вмешательства

• Биопрепарат OL-101 infusion
  OL-101 infusion will be administered to patients via IV infusion at the assigned dose.

Первичные конечные точки

• Dose-limiting toxicity (DLT) [Срок оценки: Within 28 days post CAR-T infusion]
• Treatment emergent adverse event (TEAE) incidence and severity [Срок оценки: From aphresis till 1 year after CAR-T infusion or start of a new anti-cancer therapy, whichever is earlier]

Вторичные конечные точки (12)

• Level of Immunogenicity [Срок оценки: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first]
• Level of RCL [Срок оценки: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first]
• Overall response rate (ORR) [Срок оценки: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first]
• Minimal residual disease (MRD) negative rate [Срок оценки: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first]
• Duration of response (DOR) [Срок оценки: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first]
• Progression-free survival (PFS) [Срок оценки: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first]
• Overall survival (OS) [Срок оценки: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first]
• Cmax of OL-101 [Срок оценки: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first]
• Tmax of OL-101 [Срок оценки: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first]
• AUC 0-28days of OL-101 [Срок оценки: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first]
• Serum cytokines [Срок оценки: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first]
• Serum soluble circulating BCMA (sBCMA) [Срок оценки: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first]

Критерии участия

Критерии включения

• Documented diagnosis of multiple myeloma according to the 2014 IMWG diagnostic criteria
• Relapsed/refractory multiple myeloma as defined by:

1\) 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
• ECOG 0-1
• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 3 центра

• Beijing Gobroad Boren Hospital — Пекин
• The Affiliated Hospital of Northwest University Xi'an No.3 Hospital — Xi’an
• The first affiliated hospital, College of Medicine, Zhejiang University — Ханчжоу

Идентификаторы

NCT: NCT06644118 · OL-101-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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