Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04138875
Recruitment Status : Not yet recruiting
First Posted : October 25, 2019
Last Update Posted : January 29, 2021
Sponsor:
Information provided by (Responsible Party):
Francesca Montanari, Yale University

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).


Condition or disease Intervention/treatment Phase
PTLD Lymphoid Tumor Hematopoietic/Lymphoid Cancer Plasmacytic Hyperplasia PTLD Infectious Mononucleosis Florid Follicular Hyperplasia PTLD Polymorphic PTLD Monomorphic PTLD Classical Hodgkin Lymphoma Type PTLD Drug: Rituximab Drug: Brentuximab Vedotin Drug: Bendamustine Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: This is an open label, sequential, risk stratified study.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Multicenter Open Label Risk Stratified Sequential Treatment With Rituximab, Brentuximab Vedotin and Bendamustine (RBvB) in Patients Newly Diagnosed.
Estimated Study Start Date : July 2021
Estimated Primary Completion Date : July 2023
Estimated Study Completion Date : December 2023


Arm Intervention/treatment
Active Comparator: 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.
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.
Other Name: Rituxan

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.
Other Name: Adcetris

Active Comparator: 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.
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.
Other Name: Rituxan

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.
Other Name: Adcetris

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.
Other Name: Bendamustine hydrochloride




Primary Outcome Measures :
  1. Overall response rate (ORR) (complete + partial response rate) [ Time Frame: 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.

  2. Progression free survival (PFS) rate [ Time Frame: Up to 84 days of treatment (4 cycles of treatment) ]
    Progression free survival (PFS) of the combination of rituximab, brentuximab vedotin +/-bendamustine in patients.


Secondary Outcome Measures :
  1. ORR at the end of the induction phase [ Time Frame: Up to 126 days of treatment (6 cycles of treatment) ]
    ORR at the end of the induction phase with rituximab and brentuximab vedotin (RBv) in patients

  2. Duration of response (DOR) [ Time Frame: Up to 84 days of treatment (4 cycles of treatment) ]
    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.

  3. Overall survival (OS) [ Time Frame: 3 years ]
    Overall survival (OS) of the combination of rituximab, brentuximab vedotin +/-bendamustine in patients with newly diagnosed polymorphic and monomorphic CD20+ and CD 30+ PTLD



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04138875


Locations
Layout table for location information
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06519
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55902
Contact: JAMIE JOHNSTON    507-284-2333    johnston.jamie@mayo.edu   
Principal Investigator: Thomas Haberman, MD         
Sponsors and Collaborators
Yale University
Investigators
Layout table for investigator information
Principal Investigator: Francesa Montanari, MD Yale University
Layout table for additonal information
Responsible Party: Francesca Montanari, Assistant Professor of Medicine, Yale University
ClinicalTrials.gov Identifier: NCT04138875    
Other Study ID Numbers: 2000029609
First Posted: October 25, 2019    Key Record Dates
Last Update Posted: January 29, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Infectious Mononucleosis
Hyperplasia
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Pathologic Processes
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Leukocyte Disorders
Hematologic Diseases
Rituximab
Bendamustine Hydrochloride
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action