A Phase Ib/II Clinical Study to Evaluate the Efficacy and Safety of BL-M08D1 for Injection in Combination With Immunochemotherapy in Patients With Diffuse Large B-Cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 204
- 试验地点
- 2
- 主要终点
- Recommended Phase II Dose (RP2D)
研究概览
简要总结
This Phase Ib/II study is a clinical trial to explore the efficacy and safety of BL-M08D1 for injection in combination with immunochemotherapy in patients with diffuse large B-cell lymphoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Voluntarily sign the informed consent form and comply with the protocol requirements;
- •No gender restriction;
- •Age ≥18 years and ≤75 years;
- •Expected survival time ≥3 months;
- •Patients with diffuse large B-cell lymphoma;
- •Agree to provide archived tumor tissue specimens within 3 years or fresh tissue samples;
- •Must have at least one measurable lesion;
- •Eastern Cooperative Oncology Group (ECOG) performance status score ≤2;
- •Toxicity from prior anti-tumor therapy must have recovered to ≤ Grade 1 as defined by NCI-CTCAE v6.0;
- •No severe cardiac dysfunction, with left ventricular ejection fraction ≥50%;
- •Organ function levels must meet the requirements;
- •Urine protein ≤1+ or <1000 mg/24h;
- •For premenopausal women with childbearing potential, a serum pregnancy test must be performed within 7 days before starting treatment, and the serum pregnancy test must exclude pregnancy; patients must not be breastfeeding; all enrolled trial participants must take adequate barrier contraceptive measures throughout the entire treatment period and for 6 months after treatment completion;
- •Trial participants must be able and willing to comply with the visit schedule, treatment plan, laboratory tests, and other study-related procedures specified in the protocol.
排除标准
- •Use of chemotherapy, biological therapy, immunotherapy, etc., within 4 weeks or 5 half-lives prior to the first dose;
- •History of severe heart disease or cerebrovascular disease within 6 months before screening;
- •Prolonged QT interval, complete left bundle branch block, third-degree atrioventricular block, or frequent and uncontrolled arrhythmias;
- •Active autoimmune diseases and inflammatory diseases;
- •Diagnosis of active malignancy within 5 years prior to the first dose;
- •Unstable thrombotic events requiring therapeutic intervention within 6 months prior to the first dose;
- •Hypertension inadequately controlled by antihypertensive medications;
- •Trial participants with poorly controlled blood glucose;
- •History of interstitial lung disease requiring corticosteroid therapy, or current ILD, or radiation pneumonitis of grade ≥2;
- •Use of glucocorticoids at a dose >30 mg/day prednisone or equivalent, for purposes other than control of lymphoma symptoms;
- •Concurrent pulmonary diseases resulting in clinically severe impairment of respiratory function;
- •Patients with central nervous system involvement;
- •Previous or current central nervous system disorders;
- •Contraindications to any component of the study intervention, including but not limited to previous allergic reactions;
- •Receipt of autologous hematopoietic stem cell transplantation or CAR-T cell therapy, etc., within 12 weeks prior to the first dose;
- •Positive for human immunodeficiency virus antibody, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection;
- •Active infection requiring systemic therapy within 4 weeks prior to the first study drug administration;
- •Pleural, abdominal, or pelvic effusion or pericardial effusion requiring drainage and/or accompanied by symptoms within 4 weeks prior to the first study drug administration;
- •Imaging findings indicating that the tumor has invaded or encased major blood vessels in the abdomen, chest, neck, pharynx, etc., or the pericardium or heart;
- •Use of another investigational drug within 4 weeks or 5 half-lives prior to the first dose;
- •Pregnant or breastfeeding women;
- •Other conditions that, in the investigator's opinion, make the participant unsuitable for enrollment in this clinical trial.
研究组 & 干预措施
R-GemOx or R-CHOP
Participants receive R-GemOx or R-CHOP for the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.
干预措施: Vincristine Sulfate (Drug)
R-GemOx or R-CHOP
Participants receive R-GemOx or R-CHOP for the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.
干预措施: Prednisone Acetate Tablets (Drug)
BL-M08D1+R-GemOx or BL-M08D1+R-CHOP
Participants receive BL-M08D1+R-GemOx or BL-M08D1+R-CHOP for the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.
干预措施: BL-M08D1 (Drug)
BL-M08D1+R-GemOx or BL-M08D1+R-CHOP
Participants receive BL-M08D1+R-GemOx or BL-M08D1+R-CHOP for the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.
干预措施: Gemcitabine Hydrochloride (Drug)
R-GemOx or R-CHOP
Participants receive R-GemOx or R-CHOP for the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.
干预措施: Doxorubicin Hydrochloride Liposome (Drug)
BL-M08D1+R-GemOx or BL-M08D1+R-CHOP
Participants receive BL-M08D1+R-GemOx or BL-M08D1+R-CHOP for the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.
干预措施: Rituximab (Drug)
BL-M08D1+R-GemOx or BL-M08D1+R-CHOP
Participants receive BL-M08D1+R-GemOx or BL-M08D1+R-CHOP for the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.
干预措施: Prednisone Acetate Tablets (Drug)
R-GemOx or R-CHOP
Participants receive R-GemOx or R-CHOP for the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.
干预措施: Gemcitabine Hydrochloride (Drug)
BL-M08D1+R-GemOx or BL-M08D1+R-CHOP
Participants receive BL-M08D1+R-GemOx or BL-M08D1+R-CHOP for the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.
干预措施: Oxaliplatin (Drug)
R-GemOx or R-CHOP
Participants receive R-GemOx or R-CHOP for the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.
干预措施: Rituximab (Drug)
BL-M08D1+R-GemOx or BL-M08D1+R-CHOP
Participants receive BL-M08D1+R-GemOx or BL-M08D1+R-CHOP for the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.
干预措施: Vincristine Sulfate (Drug)
R-GemOx or R-CHOP
Participants receive R-GemOx or R-CHOP for the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.
干预措施: Oxaliplatin (Drug)
BL-M08D1+R-GemOx or BL-M08D1+R-CHOP
Participants receive BL-M08D1+R-GemOx or BL-M08D1+R-CHOP for the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.
干预措施: Doxorubicin Hydrochloride Liposome (Drug)
BL-M08D1+R-GemOx or BL-M08D1+R-CHOP
Participants receive BL-M08D1+R-GemOx or BL-M08D1+R-CHOP for the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.
干预措施: Cyclophosphamide (Drug)
R-GemOx or R-CHOP
Participants receive R-GemOx or R-CHOP for the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Recommended Phase II Dose (RP2D)
时间窗: Up to approximately 24 months
The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study of BL-M08D1.
Objective Response Rate (ORR)
时间窗: Up to approximately 24 months
ORR is defined as the percentage of participants, who has a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experiences a confirmed CR or PR is according to RECIST 1.1.
次要结局
- Complete Remission Rate (CRR)(Up to approximately 24 months)
- Progression-free Survival (PFS)(Up to approximately 24 months)
- Disease Control Rate (DCR)(Up to approximately 24 months)
- Duration of Response (DOR)(Up to approximately 24 months)
- Treatment-Emergent Adverse Event (TEAE)(Up to approximately 24 months)