PTLDPhase 2NCT04138875
A Risk Stratified Sequential Treatment With Rituximab, Brentuximab Vedotin and Bendamustine (RBvB)
A Phase 2 study testing Rituximab, Brentuximab Vedotin and Bendamustine in people with PTLD and Lymphoid Tumor, run by Yale University at 2 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- PTLD, Lymphoid Tumor, Hematopoietic/Lymphoid Cancer
- What is being tested?
- Rituximab, Brentuximab Vedotin and Bendamustine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2022to Dec 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Yale University
New Haven, Connecticut, 06519
Mayo Clinic
Rochester, Minnesota, 55902
About this study
Official title: A Phase II Multicenter Open Label Risk Stratified Sequential Treatment With Rituximab, Brentuximab Vedotin and Bendamustine (RBvB) in Patients Newly Diagnosed.
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).
Read the 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.
- Conditions
- PTLD, Lymphoid Tumor, Hematopoietic/Lymphoid Cancer, Plasmacytic Hyperplasia PTLD, Infectious Mononucleosis, Florid Follicular Hyperplasia PTLD
- Being tested
- Rituximab, Brentuximab Vedotin, Bendamustine
- Medical subject headings
- Hematologic Neoplasms, Infectious Mononucleosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Also called Rituxan
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 VedotinDrug
Also called Adcetris
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.
BendamustineDrug
Also called Bendamustine hydrochloride
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Rituximab; Drug: Brentuximab Vedotin; Drug: Bendamustine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to 84 days of treatment (4 cycles of treatment)
Secondary outcomes (3)
ORR at the end of the induction phase
ORR at the end of the induction phase with rituximab and brentuximab vedotin (RBv) in patients
Measured: Up to 126 days of treatment (6 cycles of treatment)
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.
Measured: Up to 84 days of treatment (4 cycles of treatment)
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
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2019
- Study startJan 2022 (estimated)
- Primary completionSep 2023 (estimated)
- Study completionDec 2023 (estimated)
Why it stopped: Lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PTLDStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- This is an open label, sequential, risk stratified study.
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, FRANCESCA MONTANARI, Yale University
- Investigators
- Francesa Montanari, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04138875
- Sponsor's protocol ID
- 2000029609
- Status last verified
- Jun 2022
- First submitted
- 23 Oct 2019
- Last updated
- 23 Jun 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Multicenter Open Label Risk Stratified Sequential Treatment With Rituximab, Brentuximab Vedotin and Bendamustine (RBvB) in Patients Newly Diagnosed.
- ClinicalTrials.gov ID
- NCT04138875
- Acronym / sponsor ID
- 2000029609
- Conditions
- PTLD, Lymphoid Tumor, Hematopoietic/Lymphoid Cancer, Plasmacytic Hyperplasia PTLD, Infectious Mononucleosis, Florid Follicular Hyperplasia PTLD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- Jan 2022 (estimated)
- Primary completion
- Sep 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 25 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is an open label, sequential, risk stratified study.
| Arm | Type | Receives |
|---|---|---|
| Low Risk | Active comparator | Drug: Rituximab, Drug: Brentuximab VedotinLow 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. |
| High Risk | Active comparator | Drug: Rituximab, Drug: Brentuximab Vedotin, Drug: BendamustineHigh 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RituximabAlso: RituxanRituximab 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. | Drug | High Risk, Low Risk |
| Brentuximab VedotinAlso: AdcetrisBrentuximab 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. | Drug | High Risk, Low Risk |
| BendamustineAlso: Bendamustine hydrochlorideBendamustine 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. | Drug | High Risk |
Primary outcome
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.
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.
3 secondary outcomes
ORR at the end of the induction phase
Time frame: Up to 126 days of treatment (6 cycles of treatment)
Duration of response (DOR)
Time frame: Up to 84 days of treatment (4 cycles of treatment)
Overall survival (OS)
Time frame: 3 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2022.
- Individual participant dataSharing planned: No
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25BT056: Basket Study of Viral Cytotoxic T Lymphocytes
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A Phase 3 Study of Tabelecleucel for Participants With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease After Failure With Rituximab or Rituximab and Chemotherapy
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francesa Montanari, MD principal investigator
Yale University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab, Brentuximab Vedotin and Bendamustine in people with PTLD and Lymphoid Tumor, run by Yale University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 23 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate (ORR) (complete + partial response rate) (time frame: Up to 84 days of treatment (4 cycles of treatment)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2022.