NCT04138875

A Risk Stratified Sequential Treatment With Rituximab, Brentuximab Vedotin and Bendamustine (RBvB)

A Phase II Multicenter Open Label Risk Stratified Sequential Treatment With Rituximab, Brentuximab Vedotin and Bendamustine (RBvB) in Patients Newly Diagnosed.

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Yale University · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

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).

Detailed description

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.

Conditions

• PTLD
• Lymphoid Tumor
• Hematopoietic/Lymphoid Cancer
• Plasmacytic Hyperplasia PTLD
• Infectious Mononucleosis
• Florid Follicular Hyperplasia PTLD
• Polymorphic PTLD
• Monomorphic PTLD
• Classical Hodgkin Lymphoma Type PTLD

Interventions

Type	Name	Description
DRUG	Rituximab	Rituximab is dosed at 375mg/m2 as an intravenous infusion. No adjustments are necessary for hepatic or renal impairment. Dosing will be done on baseline weight and height, however in patients who experience a \>10% change in weight dosing will be readjusted.
DRUG	Brentuximab Vedotin	Brentuximab vedotin is to be given as intravenous infusion at a dose of 1.2mg/kg during induction and 1.8mg/kg with each cycle. Dose reductions to 1.2mg/kg are allowed at investigator discretion.
DRUG	Bendamustine	Bendamustine is to be given intravenously at a dose of 90mg/m2 on day 1 and day 2 of each high risk cycle. Dose reductions to 60mg/m2 are allowed at investigator discretion.

Timeline

• Start date: 2022-01-01
• Primary completion: 2023-09-01
• Completion: 2023-12-01
• First posted: 2019-10-25
• Last updated: 2022-06-23

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study