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).
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:
2000029609
- 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
Drug | Synonyms | Arms |
---|
Rituximab | Rituxan | High Risk |
Brentuximab Vedotin | Adcetris | High Risk |
Bendamustine | Bendamustine hydrochloride | High 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
Name | Type | Description | Interventions |
---|
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. | - Rituximab
- 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. | - 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: | Yale University |
Last Updated
January 29, 2021