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

Hematopoietic/Lymphoid Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04138875
• Other study ID #: 2000029609
• Status: Withdrawn
• Phase: Phase 2
• Start date: January 2022
• Est. completion date: December 2023

Study information

• Verified date: June 2022
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2023
• Est. primary completion date: September 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Age = 18 and = 70 at the time of signing informed consent

2. Patient must have histologically confirmed newly diagnosed polymorphic or monomorphic PTLD defined according to the 2016 World Health Organization (WHO) classification criteria.

3. Diagnostic archival tissue available for review and correlative studies

4. Previous solid organ or allogeneic hematopoietic stem cell transplant

5. Measurable disease

6. Eastern Cooperative Oncology Group (ECOG) performance status = 2

7. Patients must have adequate organ and marrow function

8. Negative urine or serum pregnancy test for women of childbearing potential

9. Patients must be able to understand and to sign a written consent document.

Exclusion Criteria:

1. Previous treatment for PTLD with the exception of immunosuppression reduction

2. Known involvement of the central nervous system by the PTLD

3. Known allergic reactions against foreign proteins

4. Uncontrolled inter-current illness including active infection, acute graft versus host disease and/or transplant organ rejection

5. Active concurrent malignancy with the exception of non-melanoma skin cancer, carcinoma in situ of the cervix or localized prostate cancer

6. Severe non-compensated diabetes mellitus

7. Pre-existing neuropathy grade 2 or greater

8. Pregnant or lactating

9. Psychiatric illness / social situations that would limit compliance with study requirements

10. Patients with previous hypersensitivity to Rituximab

11. Known HIV positive.

Related Conditions & MeSH terms

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

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	Yale University	New Haven	Connecticut
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Yale University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate (ORR) (complete + partial response rate)	Overall response rate (ORR) (complete + partial response rate) of the combination of rituximab, brentuximab vedotin +/-bendamustine in patients.	Up to 84 days of treatment (4 cycles of treatment)
Primary	Progression free survival (PFS) rate	Progression free survival (PFS) of the combination of rituximab, brentuximab vedotin +/-bendamustine in patients.	Up to 84 days of treatment (4 cycles of treatment)
Secondary	ORR at the end of the induction phase	ORR at the end of the induction phase with rituximab and brentuximab vedotin (RBv) in patients	Up to 126 days of treatment (6 cycles of treatment)
Secondary	Duration of response (DOR)	duration of response (DOR) of the combination of rituximab, brentuximab vedotin +/-bendamustine in patients with newly diagnosed polymorphic and monomorphic CD20+ and CD 30+ PTLD.	Up to 84 days of treatment (4 cycles of treatment)
Secondary	Overall survival (OS)	Overall survival (OS) of the combination of rituximab, brentuximab vedotin +/-bendamustine in patients with newly diagnosed polymorphic and monomorphic CD20+ and CD 30+ PTLD	3 years