Loncastuximab Tesirine and Rituximab as First-line Therapy in Patients With Post-transplant Lymphoproliferative Disorder (PLUTO)

Официальное название

A Phase 1/2 Study of Loncastuximab Tesirine and Rituximab as First-line Therapy in Patients With Post-transplant Lymphoproliferative Disorder (PLUTO)

Обзор

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).

Вмешательства

• Препарат Loncastuximab tesirine
  Lonca will be administered by IV at 75µg/kg every 3 weeks (DL1).
• Препарат Rituximab or rituximab biosimilar
  Rituximab or rituximab biosimilar will be administered by IV at 375 mg/m2 on Day 1 of every cycle. Lonca will be administered first, followed by rituximab (with a 30 min wait time between the two agents)

Первичные конечные точки

• Phase I: Define Maximum Tolerated Dose (MTD) based on the rate of dose-limiting toxicities (DLTs) during the DLT evaluation period. [Срок оценки: 4 years]
• Phase II: The complete response (CR) rate after 4 cycles of lonca-R per Lugano 2014 criteria1. [Срок оценки: 4 years]

Вторичные конечные точки (5)

• The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by type, severity (as defined by the NIH CTCAE, version 6.0), seriousness, duration, and relationship to study treatment. [Срок оценки: 4 years]
• The overall response rate (ORR) after 4 cycles of lonca-R. [Срок оценки: 4 years]
• The best complete response (CR) rate is defined as CR at the completion of 4 cycles of lonca-R or 4 cycles of lonca-R and 4 cycles of consolidation of rituximab monotherapy (every 3 weeks) in subjects with B-cell PTLD. [Срок оценки: 4 years]
• Median and two year progression-free survival (PFS). PFS will be as defined as the time from study drug initiation to the time of documented disease progression (as assessed by Lugano Criteria), or death from any cause. [Срок оценки: 4 years]
• Median and two year overall survival (OS). OS is defined as the time from initiation of treatment until death from any cause. [Срок оценки: 4 years]

Критерии участия

Критерии включения

• 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 ≤ 2.
• Adequate organ function as defined as:

• Hematologic:

• Absolute neutrophil count (ANC) ≥ 1000/mm3
• Platelet count ≥ 75,000/mm3
• Hemoglobin ≥ 8 g/dL
• Hepatic:

• 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
• Renal:

• 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 5.4.2.
• 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

Критерии исключения

• 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 6.8.1. 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.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Huntsman Cancer Institute at University of Utah — Salt Lake City

Идентификаторы

NCT: NCT07573436 · HCI198713

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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