A Phase 1/2 Study of Loncastuximab Tesirine and Rituximab as First-line Therapy in Patients With Post-transplant Lymphoproliferative Disorder (PLUTO)
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 23
- 试验地点
- 1
研究概览
简要总结
The purpose of phase I of this clinical trial is to learn the recommended dose of the drugs loncastuximab tesirine and rituximab in participants with post-transplant lymphoproliferative disorders (PTLD).
The purpose of phase II of this clinical trial is to learn if the drugs loncastuximab tesirine and rituximab are effective in participants with post-transplant lymphoproliferative disorders (PTLD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Subject aged ≥ 18 years.
- •Histologically confirmed B-cell PTLD (monomorphic and polymorphic) following solid organ transplantation; with or without EBV association.
- •-Note: Subjects with classic Hodgkin-like PTLD are excluded.
- •Measurable disease as defined by the 2014 Lugano Classification as assessed by positron-emission tomography (PET)- computed tomography (CT) or by CT or magnetic resonance imaging (MRI) if the tumor is not fluorodeoxyglucose (FDG)-avid on screening
- •ECOG Performance Status ≤
- •Adequate organ function as defined as:
- •Hematologic:
- •Absolute neutrophil count (ANC) ≥ 1000/mm3
- •Platelet count ≥ 75,000/mm3
- •Hemoglobin ≥ 8 g/dL
- •Bilirubin ≤1.5 x upper limit of normal (ULN) or ≤3 x ULN with document liver involvement and/ or Gilbert's disease
- •Transaminases (AST or ALT) ≤ 3 x ULN or ≤ 5 x ULN with documented liver involvement
- •Estimated creatinine clearance ≥ 60 mL/min by Cockcroft-Gault formula.
- •For female subjects: Negative pregnancy test or evidence of post-menopausal status. The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
- •Women < 50 years of age:
- •Amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and
- •Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution; or
- •Underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
- •Women ≥ 50 years of age:
- •Amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments; or
- •Had radiation-induced menopause with last menses >1 year ago; or
- •Had chemotherapy-induced menopause with last menses >1 year ago; or
- •Underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).
- •Female subjects of childbearing potential and male subjects with a sexual partner of childbearing potential must agree to use a highly effective method of contraception and the lactation requirements as described in Sections 5.4.1 and 5.4.
- •Subjects or their legal representatives must be able to read, understand, and provide informed consent to participate in the trial.
- •Willing and capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol
排除标准
- •PTLD following liquid transplantation
- •CNS involvement
- •Prior treatment for PTLD with the exception of radiation, antivirals, steroids and reduced immunosuppression
- •Human immunodeficiency virus (HIV) infection
- •Major surgery within 4 weeks prior to enrolment
- •History of bleeding diathesis (e.g., von Willebrand's disease), hemophilia, or active bleeding.
- •Subjects with chronic liver disease with hepatic impairment Child-Pugh class C
- •Pregnant or lactating or intending to become pregnant during the study
- •Active autoimmune disease which, in the opinion of the investigator, may negatively impact subject safety or interfere with study participation.
- •The diagnosis of another malignancy which, in the opinion of the investigator, is likely to negatively impact subject safety or interfere with study participation.
- •Significant medical diseases or conditions including those requiring substantial changes in concomitant medications, as assessed by the investigator, that would substantially increase the risk-to-benefit ratio of participating in the study. This includes, but is not limited to the following conditions:
- •Cardiovascular disorders:
- •Congestive heart failure New York Heart Association Class III or IV, unstable angina pectoris, serious cardiac arrhythmias.
- •Myocardial infarction (MI) within 6 months before the first dose.
- •QTc prolongation defined as a QTcF > 480 ms.
- •Congenital long QT syndrome or a corrected QT measure (QTc) interval of >480 ms at screening (unless secondary to pacemaker or bundle branch block).
- •Grade 2 or higher edema (peripheral, pleural or ascites)
- •Grade 1 or higher pericardial effusion
- •Severe pulmonary disease
- •Uncontrolled diabetes mellitus
- •Severely immunocompromised state
- •Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures.
- •Active systemic bacterial, viral, fungal, or other infection requiring systemic treatment at time of screening
- •Subjects with evidence of active hepatitis B infection, based on positive surface antigen or Hepatitis B DNA PCR are excluded. Subjects who are Hepatitis B core antibody positive must take prophylaxis with entecavir or equivalent and be willing to undergo monthly Hepatitis B DNA PCR testing
- •Active hepatitis C infection
- •Grade 2 or higher rash
- •Clinically significant fluid accumulation in the third space
- •Subjects taking prohibited medications as described in Section 6.8.
- •A washout period of prohibited medications for a period of at least five half-lives or as clinically indicated should occur before the start of treatment.
研究组 & 干预措施
Dose Level 1 (starting dose): SD or PD
Dose Level 1:
- Loncastuximab tesirine: 0.075 mg/kg IV every 3 weeks
- Rituximab: 375 mg/m2 IV
This arm included participants who had SD (Stable Disease) or PD (Progressive Disease) after the first 6 weeks of treatment.
Lonca-R will be administered for 4 cycles with response assessment at 6 weeks (+/- 1 week) following the last Lonca-R treatment. If they do not achieve a response, they will come off the study but will be monitored for survival.
干预措施: Rituximab or rituximab biosimilar (Drug)
Dose Level 1 (starting dose): PR
Dose Level 1:
- Loncastuximab tesirine: 0.075 mg/kg IV every 3 weeks
- Rituximab: 375 mg/m2 IV
This arm included participants who had a Partial Response (PR) after the first 6 weeks of treatment.
Lonca-R will be administered for 4 cycles with response assessment at 6 weeks (+/- 1 week) following the last Lonca-R treatment. If they achieve PR, they will have the option to receive either rituximab consolidation or R-CHOP (at the physician's discretion).
干预措施: Rituximab or rituximab biosimilar (Drug)
Dose Level 1 (starting dose): CR
Dose Level 1:
- Loncastuximab tesirine: 0.075 mg/kg IV every 3 weeks
- Rituximab: 375 mg/m2 IV
This arm included participants who had a Complete Response (CR) after the first 6 weeks of treatment.
Lonca-R will be administered for 4 cycles with response assessment at 6 weeks (+/- 1 week) following the last Lonca-R treatment. If they achieve a CR after 4 cycles of Lonca-R, they will receive rituximab consolidation (SOC).
干预措施: Rituximab or rituximab biosimilar (Drug)
Dose Level 2: PR
Dose Level 2:
- Loncastuximab tesirine: 0.15 mg/kg IV every 3 weeks for the first 2 cycles, then 0.075 mg/kg starting C3
- Rituximab: 375 mg/m2 IV
This arm included participants who had a Partial Response (PR) after the first 6 weeks of treatment.
Lonca-R will be administered for 4 cycles with response assessment at 6 weeks (+/- 1 week) following the last Lonca-R treatment. If they achieve PR, they will have the option to receive either rituximab consolidation or R-CHOP (at the physician's discretion).
干预措施: Rituximab or rituximab biosimilar (Drug)
Dose Level 2: SD or PD
Dose Level 2:
- Loncastuximab tesirine: 0.15 mg/kg IV every 3 weeks for the first 2 cycles, then 0.075 mg/kg starting C3
- Rituximab: 375 mg/m2 IV
This arm included participants who had SD (Stable Disease) or PD (Progressive Disease) after the first 6 weeks of treatment.
Lonca-R will be administered for 4 cycles with response assessment at 6 weeks (+/- 1 week) following the last Lonca-R treatment. If they do not achieve a response, they will come off the study but will be monitored for survival.
干预措施: Rituximab or rituximab biosimilar (Drug)
Dose Level 2: SD or PD
Dose Level 2:
- Loncastuximab tesirine: 0.15 mg/kg IV every 3 weeks for the first 2 cycles, then 0.075 mg/kg starting C3
- Rituximab: 375 mg/m2 IV
This arm included participants who had SD (Stable Disease) or PD (Progressive Disease) after the first 6 weeks of treatment.
Lonca-R will be administered for 4 cycles with response assessment at 6 weeks (+/- 1 week) following the last Lonca-R treatment. If they do not achieve a response, they will come off the study but will be monitored for survival.
干预措施: Loncastuximab tesirine (Drug)
Dose Level 2: CR
Dose Level 2:
- Loncastuximab tesirine: 0.15 mg/kg IV every 3 weeks for the first 2 cycles, then 0.075 mg/kg starting C3
- Rituximab: 375 mg/m2 IV
This arm included participants who had a Complete Response (CR) after the first 6 weeks of treatment.
Lonca-R will be administered for 4 cycles with response assessment at 6 weeks (+/- 1 week) following the last Lonca-R treatment. If they achieve a CR after 4 cycles of Lonca-R, they will receive rituximab consolidation (SOC).
干预措施: Rituximab or rituximab biosimilar (Drug)
Dose Level 1 (starting dose): PR
Dose Level 1:
- Loncastuximab tesirine: 0.075 mg/kg IV every 3 weeks
- Rituximab: 375 mg/m2 IV
This arm included participants who had a Partial Response (PR) after the first 6 weeks of treatment.
Lonca-R will be administered for 4 cycles with response assessment at 6 weeks (+/- 1 week) following the last Lonca-R treatment. If they achieve PR, they will have the option to receive either rituximab consolidation or R-CHOP (at the physician's discretion).
干预措施: Loncastuximab tesirine (Drug)
Dose Level 1 (starting dose): SD or PD
Dose Level 1:
- Loncastuximab tesirine: 0.075 mg/kg IV every 3 weeks
- Rituximab: 375 mg/m2 IV
This arm included participants who had SD (Stable Disease) or PD (Progressive Disease) after the first 6 weeks of treatment.
Lonca-R will be administered for 4 cycles with response assessment at 6 weeks (+/- 1 week) following the last Lonca-R treatment. If they do not achieve a response, they will come off the study but will be monitored for survival.
干预措施: Loncastuximab tesirine (Drug)
Dose Level 1 (starting dose): CR
Dose Level 1:
- Loncastuximab tesirine: 0.075 mg/kg IV every 3 weeks
- Rituximab: 375 mg/m2 IV
This arm included participants who had a Complete Response (CR) after the first 6 weeks of treatment.
Lonca-R will be administered for 4 cycles with response assessment at 6 weeks (+/- 1 week) following the last Lonca-R treatment. If they achieve a CR after 4 cycles of Lonca-R, they will receive rituximab consolidation (SOC).
干预措施: Loncastuximab tesirine (Drug)
Dose Level 2: CR
Dose Level 2:
- Loncastuximab tesirine: 0.15 mg/kg IV every 3 weeks for the first 2 cycles, then 0.075 mg/kg starting C3
- Rituximab: 375 mg/m2 IV
This arm included participants who had a Complete Response (CR) after the first 6 weeks of treatment.
Lonca-R will be administered for 4 cycles with response assessment at 6 weeks (+/- 1 week) following the last Lonca-R treatment. If they achieve a CR after 4 cycles of Lonca-R, they will receive rituximab consolidation (SOC).
干预措施: Loncastuximab tesirine (Drug)
Dose Level 2: PR
Dose Level 2:
- Loncastuximab tesirine: 0.15 mg/kg IV every 3 weeks for the first 2 cycles, then 0.075 mg/kg starting C3
- Rituximab: 375 mg/m2 IV
This arm included participants who had a Partial Response (PR) after the first 6 weeks of treatment.
Lonca-R will be administered for 4 cycles with response assessment at 6 weeks (+/- 1 week) following the last Lonca-R treatment. If they achieve PR, they will have the option to receive either rituximab consolidation or R-CHOP (at the physician's discretion).
干预措施: Loncastuximab tesirine (Drug)