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

NCT04138875 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 2000029609
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief 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).

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

Outcome Measures

Primary Outcomes (2)

• 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)

• 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 Outcomes (3)

• 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

Study Arms (2)

Low Risk

ACTIVE COMPARATOR

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.

Drug: Rituximab; Drug: Brentuximab Vedotin

High Risk

ACTIVE COMPARATOR

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.

Drug: Rituximab; Drug: Brentuximab Vedotin; Drug: Bendamustine

Interventions

Rituximab DRUG

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.

Also known as: Rituxan

High Risk; Low Risk

Brentuximab Vedotin DRUG

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.

Also known as: Adcetris

High Risk; Low Risk

Bendamustine DRUG

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.

Also known as: Bendamustine hydrochloride

High Risk

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yale University: lead

Study Sites (2)

Yale University

New Haven, Connecticut, 06519, United States

Location

Mayo Clinic

Rochester, Minnesota, 55902, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms; Infectious Mononucleosis

Interventions

Rituximab; Brentuximab Vedotin; Bendamustine Hydrochloride

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Leukocyte Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Oligopeptides; Peptides; Antibodies, Monoclonal, Humanized; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Francesa Montanari, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Model Details: This is an open label, sequential, risk stratified study.

Study Record Dates

• First Submitted: October 23, 2019
• First Posted: October 25, 2019
• Study Start: January 1, 2022
• Primary Completion: September 1, 2023
• Study Completion: December 1, 2023
• Last Updated: June 23, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)