A Phase II Multicenter Open Label Risk Stratified Sequential Treatment With Rituximab, Brentuximab Vedotin and Bendamustine (RBvB) in Patients Newly Diagnosed.
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- Overall response rate (ORR) (complete + partial response rate)
研究概览
简要总结
This is an open label, risk-stratified, sequential treatment, phase 2 study of newly diagnosed post-transplant lymphoproliferative disorders with positive CD20 and CD30 expression. It includes an induction phase with rituximab and brentuximab vedotin (RBv), followed by a treatment phase with RBv or RBv in combination with bendamustine (RBvB) based on response to induction.
The primary end point is treatment efficacy measured as the overall response rate (ORR) and progression free survival (PFS).
详细描述
Post-Transplant Lymphoproliferative Disorders (PTLD) are defined by the revised 2017 edition of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues as "lymphoid or plasmacytic proliferations that develop as a consequence of immunosuppression in a recipient of a solid organ, bone marrow or stem cell allograft". Within this definition 4 distinct categories exist, including: (1) Non-destructive PTLDs (plasmacytic hyperplasia, infectious mononucleosis, and florid follicular hyperplasia) (2) Polymorphic PTLD; (3) Monomorphic PTLD and (4) Classical Hodgkin Lymphoma type PTLD.
The incidence of PTLD varies between different transplanted organs. Across all transplants monomorphic PTLD is the most common accounting for 75% of all cases. Lymphoma derived of B- cell origin account for the majority of cases (70%), while T-cell neoplasms represent a small minority (5%). Within monomorphic PTLD 50% of cases demonstrate association with the Epstein Barr Virus (EBV). Polymorphic PTLD accounts for 15-20% of all PTLD cases with the majority demonstrating EBV involvement. Early lesions account for 5% of PTLD and are all uniformly associated with EBV as are all the cases of Classic Hodgkin Lymphoma type PTLD.
The current understanding of the pathogenesis of PTLD is incomplete. Despite concerted efforts, the investigators are unable to predict who will develop PTLD and do not understand why only 1 - 2% of all transplant recipients develop these disorders.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 and ≤ 70 at the time of signing informed consent
- •Patient must have histologically confirmed newly diagnosed polymorphic or monomorphic PTLD defined according to the 2016 World Health Organization (WHO) classification criteria.
- •Diagnostic archival tissue available for review and correlative studies
- •Previous solid organ or allogeneic hematopoietic stem cell transplant
- •Measurable disease
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- •Patients must have adequate organ and marrow function
- •Negative urine or serum pregnancy test for women of childbearing potential
- •Patients must be able to understand and to sign a written consent document.
排除标准
- •Previous treatment for PTLD with the exception of immunosuppression reduction
- •Known involvement of the central nervous system by the PTLD
- •Known allergic reactions against foreign proteins
- •Uncontrolled inter-current illness including active infection, acute graft versus host disease and/or transplant organ rejection
- •Active concurrent malignancy with the exception of non-melanoma skin cancer, carcinoma in situ of the cervix or localized prostate cancer
- •Severe non-compensated diabetes mellitus
- •Pre-existing neuropathy grade 2 or greater
- •Pregnant or lactating
- •Psychiatric illness / social situations that would limit compliance with study requirements
- •Patients with previous hypersensitivity to Rituximab
- •Known HIV positive.
研究组 & 干预措施
Low Risk
Low risk patients (those in complete response (CR) after induction) will receive rituximab (375mg/m2) and brentuximab vedotin (1.8mg/m2) on day 1 of 21 day cycles, for 4 cycles.
干预措施: Rituximab (Drug)
Low Risk
Low risk patients (those in complete response (CR) after induction) will receive rituximab (375mg/m2) and brentuximab vedotin (1.8mg/m2) on day 1 of 21 day cycles, for 4 cycles.
干预措施: Brentuximab Vedotin (Drug)
High Risk
High risk patients (those who do not achieve a CR after induction), will receive rituximab (375mg/m2) and brentuximab vedotin (1.8mg/m2) on day 1 and bendamustine (90mg/m2) on day 1-2 of 21 day cycles for up to 8 cycles. Interim imaging will be performed in cycle 4 (days 14-21) and patients achieving CR will receive additional 2 cycles for a total of 6, patients achieving partial response (PR) will receive 4 additional cycles.
干预措施: Rituximab (Drug)
High Risk
High risk patients (those who do not achieve a CR after induction), will receive rituximab (375mg/m2) and brentuximab vedotin (1.8mg/m2) on day 1 and bendamustine (90mg/m2) on day 1-2 of 21 day cycles for up to 8 cycles. Interim imaging will be performed in cycle 4 (days 14-21) and patients achieving CR will receive additional 2 cycles for a total of 6, patients achieving partial response (PR) will receive 4 additional cycles.
干预措施: Brentuximab Vedotin (Drug)
High Risk
High risk patients (those who do not achieve a CR after induction), will receive rituximab (375mg/m2) and brentuximab vedotin (1.8mg/m2) on day 1 and bendamustine (90mg/m2) on day 1-2 of 21 day cycles for up to 8 cycles. Interim imaging will be performed in cycle 4 (days 14-21) and patients achieving CR will receive additional 2 cycles for a total of 6, patients achieving partial response (PR) will receive 4 additional cycles.
干预措施: Bendamustine (Drug)
结局指标
主要结局
Overall response rate (ORR) (complete + partial response rate)
时间窗: Up to 84 days of treatment (4 cycles of treatment)
Overall response rate (ORR) (complete + partial response rate) of the combination of rituximab, brentuximab vedotin +/-bendamustine in patients.
Progression free survival (PFS) rate
时间窗: Up to 84 days of treatment (4 cycles of treatment)
Progression free survival (PFS) of the combination of rituximab, brentuximab vedotin +/-bendamustine in patients.
次要结局
- ORR at the end of the induction phase(Up to 126 days of treatment (6 cycles of treatment))
- Duration of response (DOR)(Up to 84 days of treatment (4 cycles of treatment))
- Overall survival (OS)(3 years)
研究者
FRANCESCA MONTANARI
Assistant Professor of Medicine
Yale University