LMY-920 for Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- To determine recommended phase II dose of human LMY-920.
研究概览
简要总结
Therapy with chimeric antigen receptor T (CAR-T) cells has demonstrated activity against refractory lymphoma, however not all tumors respond or remain in response to CD19 targeted CAR-T cells. We posit that CAR-T cells expressing BAFF (BAFF CAR-T cells) can become another strategy to treat refractory lymphoma, even after relapse following cluster of differentiation antigen 19 (CD19) targeting CAR-T treatment.
This phase 1 study will evaluate safe dose and provide initial signal of the activity of BAFF CAR-T cells against relapsed non-Hodgkin lymphoma using a single lymphodepletion regimen and using a BAFF CAR-T cell manufacturing process.
详细描述
LMY-920 is an autologous CAR-T cell therapy consisting of autologous cluster of differentiation 4 (CD4) positive and cluster of differentiation 8 (CD8) positive human T cells that are genetically engineered using the non-viral transposon system to express the BAFF-ligand CAR-T that target BAFF receptor family members to eliminate malignant B cells.
BAFF receptor family includes B-cell activating factor receptor (BR3), B-cell maturation antigen (BCMA) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI). These receptors are present on non-Hodgkin lymphoma.
The goal of LMY-920-001 phase 1 study is to find recommended phase 2 dose of LMY-920 for treatment of patients with relapsed or refractory non-Hodgkin lymphoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must have histologically confirmed non-Hodgkin lymphoma relapsed after 2 or more lines of therapy or disease refractory to chemotherapy (defined as progressive disease or stable disease lasting ≤6 months, as best response to most recent chemotherapy regimen; or disease progression or recurrence ≤12 months after prior autologous stem cell transplantation (ASCT).
- •No evidence of central nervous system (CNS) lymphoma.
- •Male or female > 18 years of age.
- •Eastern Cooperative Oncology Group Performance status ≤
- •At least one measurable lesion.
- •>2 weeks since prior radiation therapy or systemic therapy at the time of leukapheresis.
- •Total bilirubin ≤ 1.5 mg/dL (except in patients with Gilbert's syndrome).
- •Aspartate aminotransferase/alanine transferase ≤ 2.5 X institutional upper limit of normal.
- •Serum creatinine < 1.5 mg/dL.
- •Cardiac ejection fraction of >50%, and no evidence of pericardial effusion, as determined by an echocardiogram.
- •Adequate pulmonary function as defined as pulse oximetry ≥ 92% on room air.
- •Subjects (or legal guardians) must have the ability to understand and the willingness to sign a written informed consent document.
- •For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of < 1% per year during the treatment period and for at least 90 days after the BAFF CAR-T cell infusion.
- •For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm.
排除标准
- •ASCT within 6 weeks of informed consent.
- •History of allogeneic hematopoietic stem cell transplantation.
- •Active graft-versus-host disease.
- •Active central nervous system or meningeal involvement by lymphoma or leukemia.
- •Active malignancy, other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast).
- •Less than 28 days elapsed between prior treatment with investigational agent(s) and the day of lymphocyte collection.
- •New York Heart Association class IV congestive heart failure.
- •Cardiovascular disorders including unstable angina pectoris, clinically significant cardiac arrhythmias, myocardial infarction or stroke (including transient ischemic attack, or other ischemic event) within 6 months prior to registration.
- •Active infection requiring intravenous systemic treatment.
- •HIV seropositivity.
- •Pregnant or breastfeeding women.
- •Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy.
- •Serologic status reflecting active hepatitis B or C infection.
- •Patients with history of clinically relevant CNS pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia and Parkinson's disease.
- •Subjects with uncontrolled intercurrent illness.
- •Known additional malignancies which require systemic treatment.
- •History of autoimmune disease with requirement of immunosuppressive medications (other than low dose steroids) within 6 months.
研究组 & 干预措施
LMY-920 dose escalation
Open label, dose escalation study with up to four dose levels of LMY-920. The maximum tolerated dose (MTD) of LMY-920 will be determined using dose-escalation 3+3 design.
干预措施: BAFF CAR-T (Drug)
结局指标
主要结局
To determine recommended phase II dose of human LMY-920.
时间窗: 24 months
Maximum tolerated dose.
次要结局
- To determine the objective response rate .(24 months)
- To determine the duration of response.(24 months)
- To determine incidence of anti- LMY-920 antibodies.(24 months)
- To determine the overall survival.(24 months)
- To establish toxicity profile for the infusion of LMY-920.(24 months)
- To determine the complete response rate.(24 months)
- To determine the progression-free survival.(24 months)
- To determine incidence of adverse events.(24 months)