A Pilot Study of Loncastuximab Tesirine in Specific Populations of Relapsed/Refractory B-Cell Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Overall response rate (ORR)
研究概览
简要总结
This phase II trial tests whether loncastuximab tesirine works to shrink tumors in patients with B-cell malignancies that have come back (relapsed) or does not respond to treatment (refractory). Loncastuximab tesirine is a monoclonal antibody, called loncastuximab, linked to a chemotherapy drug, called tesirine. Loncastuximab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD19 receptors, and delivers tesirine to kill them.
详细描述
OUTLINE:
Patients receive loncastuximab tesirine intravenously (IV) over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone marrow biopsy and aspiration throughout the study.
After completion of study treatment, patients are followed up for 5 years.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patient aged 18 years or older
- •Disease-specific criteria:
- •Group 2: Relapsed/refractory. CD19+ B-cell non-Hodgkin lymphoma (B-NHL) excluding Waldenstrom's macroglobulinemia and marginal zone lymphoma, (at least 1 prior therapy, and no alternative with a more favorable benefit/risk ratio in the judgment of the treating investigator.
- •Group 3: CD19+ diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), or mantle cell lymphoma (MCL) relapsing after chimeric antigen receptor (CAR) T-cell therapy or allogeneic transplant (at least 30 days from CAR T/transplant)
- •Have measurable nodal or extranodal disease, including at least 1 disease site measuring 1.5 cm in longest dimension; or splenomegaly; or histologic marrow involvement for marrow-only presentations
- •Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) performance scale (PS)
- •Absolute neutrophil count (ANC) >= 1.0 x 10^3/uL (off growth factors at least 72 hours), unless due to marrow involvement by lymphoma in which case ANC must be >= 0.5 x 10^3/uL
- •Platelet count >= 75 x 10^3/uL without transfusion in the prior 7 days, unless due to disease including splenomegaly in which case platelet count must be >= 50 x 10^3/uL
- •Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) =< 3 x the upper limit of normal (ULN)
- •Total bilirubin =< 1.5 x ULN (patients with known Gilbert's syndrome may have a total bilirubin up to =< 3 x ULN)
- •Blood creatinine =< 2.0 x ULN or calculated creatinine clearance >= 50 mL/min by the Cockcroft and Gault equation
- •Negative beta-human chorionic gonadotropin (beta-HCG) pregnancy test within 7 days prior to start of study drug (cycle 1 day 1 [C1D1]) for women of childbearing potential
- •Women of childbearing potential must agree to use a highly effective method of contraception from the time of giving informed consent until at least 10 months after the last dose of loncastuximab tesirine
- •Men with female partners who are of childbearing potential must agree that they will use a condom from the time of giving informed consent until at least 7 months after the patient receives his last dose of loncastuximab tesirine
排除标准
- •Previous treatment with loncastuximab tesirine
- •Known history of hypersensitivity to loncastuximab tesirine
- •Active second primary malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy
- •Uncontrolled graft-versus-host disease
- •Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive or hepatitis B virus [HBV] deoxyribonucleic acid [DNA] detectable) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
- •Is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 9 months after the last dose of trial treatment
- •Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath)
- •Lymphoma with active central nervous system (CNS) involvement at the time of screening, including active leptomeningeal disease. A history of treated CNS disease permitted
- •Significant medical comorbidities, including but not limited to unstable angina, congestive heart failure (New York Heart Association class III or greater), uncontrolled atrial or ventricular cardiac arrhythmia, that would, in the Investigator's judgment, make the patient inappropriate for study participation or put the patient at risk
- •Major surgery, radiotherapy, chemotherapy or other anti-neoplastic therapy within 14 days prior to start of study drug (C1D1)
- •Use of any other experimental medication within 14 days prior to start of study drug (C1D1)
- •Planned live vaccine administration after starting study drug (C1D1)
- •Any other significant medical illness, abnormality, or condition that would, in the investigator's judgment, make the patient inappropriate for study participation or put the patient at risk
- •Is currently participating in a study and receiving an investigational agent or is using an investigational device within 4 weeks of the first dose of treatment
研究组 & 干预措施
Treatment (loncastuximab tesirine)
Patients receive loncastuximab tesirine IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone marrow biopsy and aspiration throughout the study.
干预措施: Bone Marrow Biopsy (Procedure)
Treatment (loncastuximab tesirine)
Patients receive loncastuximab tesirine IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone marrow biopsy and aspiration throughout the study.
干预措施: Bone Marrow Aspiration (Procedure)
Treatment (loncastuximab tesirine)
Patients receive loncastuximab tesirine IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone marrow biopsy and aspiration throughout the study.
干预措施: Loncastuximab Tesirine (Biological)
结局指标
主要结局
Overall response rate (ORR)
时间窗: Up to 5 years
According to the 2014 Lugano classification Cheson 20146 as determined by local review; ORR is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR).
次要结局
- Clinical benefit rate(Up to 5 years)
- Rates of grade 3-5 adverse event(Up until 30 days after the last dose of the last study drug)
- Progression free survival(Time between start of treatment and the first documentation of recurrence, progression, or death, assessed up to 5 years)
- Overall survival(Time between the start of treatment and death from any cause, assessed up to 5 years)
- Duration or response(Time from the first documentation of tumor response to disease progression or death, assessed up to 5 years)
- Incidence of grade 3-5 drug-related toxicity(Up until 30 days after the last dose of the last study drug)
- Rate of discontinuation due to adverse events(Up until 30 days after the last dose of the last study drug)