Clinical Trials /

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

NCT04138875

Description:

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).

Related Conditions:
  • Post-Transplant Lymphoproliferative Disorder
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Risk Stratified Sequential Treatment With Rituximab, Brentuximab Vedotin and Bendamustine (RBvB)
  • 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 IDs

  • ORG STUDY ID: AAAS3998
  • NCT ID: NCT04138875

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

DrugSynonymsArms
RituximabRituxanHigh Risk
Brentuximab VedotinAdcetrisHigh Risk
BendamustineBendamustine hydrochlorideHigh Risk

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Low RiskActive ComparatorLow 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.
  • Rituximab
  • Brentuximab Vedotin
High RiskActive ComparatorHigh 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.
  • Rituximab
  • Brentuximab Vedotin
  • Bendamustine

Eligibility 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.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate (ORR) (complete + partial response rate)
Time Frame:Up to 84 days of treatment (4 cycles of treatment)
Safety Issue:
Description:Overall response rate (ORR) (complete + partial response rate) of the combination of rituximab, brentuximab vedotin +/-bendamustine in patients.

Secondary Outcome Measures

Measure:ORR at the end of the induction phase
Time Frame:Up to 126 days of treatment (6 cycles of treatment)
Safety Issue:
Description:ORR at the end of the induction phase with rituximab and brentuximab vedotin (RBv) in patients
Measure:Duration of response (DOR)
Time Frame:Up to 84 days of treatment (4 cycles of treatment)
Safety Issue:
Description: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.
Measure:Overall survival (OS)
Time Frame:3 years
Safety Issue:
Description:Overall survival (OS) of the combination of rituximab, brentuximab vedotin +/-bendamustine in patients with newly diagnosed polymorphic and monomorphic CD20+ and CD 30+ PTLD

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Francesca Montanari

Last Updated

October 23, 2019