Polatuzumab Vedotin and Combination Chemotherapy With or Without Glofitamab for the Treatment of Untreated Aggressive Large B-cell Lymphoma
A Pilot Study to Estimate the Safety and Tolerability of the Combination of Polatuzumab Vedotin, With or Without Glofitamab, With Dose Adjusted Rituximab, Etoposide, Cyclophosphamide, and Doxorubicin (PERCH) for Upfront Treatment of Aggressive B-Cell Non-Hodgkin Lymphomas
3 other identifiers
interventional
56
1 country
1
Brief Summary
This phase I trial studies the side effects of polatuzumab vedotin when given with combination chemotherapy with or without glofitamab for the treatment of patients with untreated large B-cell lymphoma that grows and spreads quickly and has severe symptoms (aggressive). Polatuzumab vedotin is a monoclonal antibody, polatuzumab, linked to a toxic agent called vedotin. Polatuzumab attaches to CD79B positive cancer cells in a targeted way and delivers vedotin to kill them. Glofitamab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Drugs used in combination chemotherapy such as etoposide, cyclophosphamide, and doxorubicin work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Rituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Anti-inflammatory drugs, such as prednisone, lower the body's immune response and are used with other drugs in the treatment of some types of cancer. Giving polatuzumab vedotin in combination chemotherapy with or without glofitamab may help treat patients with aggressive large B-cell lymphoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Oct 2020
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 14, 2020
CompletedFirst Posted
Study publicly available on registry
January 18, 2020
CompletedStudy Start
First participant enrolled
October 27, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2031
March 3, 2026
February 1, 2026
6.1 years
January 14, 2020
February 27, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Incidence of adverse events
Will estimate the safety and tolerability of polatuzumab vedotin when added to dose-adjusted-etoposide, prednisone, vincristine (Oncovin), cyclophosphamide, doxorubicin-rituximab (DA-EPCH-R) with or without glofitamab, chemoimmunotherapy.
Up to 30 days after last dose of polatuzumab or first administration of alternate therapy
Secondary Outcomes (1)
The proportion of patients who are unable to complete 6 cycles of therapy for reasons other than disease progression
Up to 18 weeks
Study Arms (2)
Arm A (polatuzumab vedotin, chemotherapy) [CLOSED TO ACCRUAL 05/23/2024]
EXPERIMENTALPatients receive rituximab IV on day 1, polatuzumab vedotin IV on day 1, prednisone PO BID on days 1-5, etoposide IV on days 1-4, doxorubicin IV on days 1-4, and cyclophosphamide IV on day 5. Patients also receive filgrastim SC 24-72 hours after the last dose of each treatment cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo MUGA scan or echocardiography during screening and FDG PET, CT scan, bone marrow biopsy and aspiration and blood sample collection throughout the study.
Arm B (polatuzumab vedotin, glofitamab, chemotherapy)
EXPERIMENTALPatients receive rituximab IV on day 1, polatuzumab vedotin IV on day 1, prednisone PO BID on days 1-5, etoposide IV on days 1-4, doxorubicin IV on days 1-4, and cyclophosphamide IV on day 5. Starting with cycle 2, patients also receive glofitamab, over 4 hours, on day 1 and 8 of cycle 2 and day 1 of subsequent cycles. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo MUGA scan or echocardiography during screening and FDG PET, CT scan, bone marrow biopsy and aspiration and blood sample collection throughout the study.
Interventions
Undergo FDG-PET scan
Undergo bone marrow biopsy
Undergo blood sample collection
Undergo bone marrow aspiration
Given IV
Given IV
Given PO
Given IV
Given IV
Given IV
Given IV
Undergo MUGA scan
Undergo CT scan
Undergo echocardiography
Eligibility Criteria
You may qualify if:
- Untreated aggressive B-cell large-B cell lymphoma (non-Hodgkin lymphoma) with adverse features that may predict sub-optimal response to rituximab-cyclophosphamide, doxorubicin (hydroxydaunorubicin), vincristine (Oncovin), prednisone (R-CHOP) and in the opinion of the investigator would be treated with DA-EPOCH-R as standard of care. Subjects must be planned to receive full course (6 cycles) chemoimmunotherapy as per clinical standard of care. Composite lymphomas are not excluded provided that the subject has not receive prior systemic therapy for the indolent component and would receive DA-EPOCH-R as the standard of care regimen for the aggressive component. Eligible histologies based on 2016 World Health Organization (WHO) classification include:
- High grade B-cell lymphoma with MYC and BCL2 and/or BCL6 translocations
- High grade B-cell lymphoma, not otherwise specified (NOS)
- Diffuse large B-cell lymphoma (DLBCL) NOS
- Primary mediastinal B-cell lymphoma
- T-cell/histiocyte-rich large-B-cell lymphoma
- Epstein-Barr virus (EBV) + DLBCL, NOS
- ALK+ large B-cell lymphoma (must be CD20+)
- B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma
- Be willing and able to provide written informed consent for the trial
- Be \>= 18 years of age on day of signing informed consent
- Have measurable disease, including at least 1 nodal site measuring 1.5 cm or 1 extranodal site measuring 1.0 cm in longest dimension on computed tomography (CT) or fluorodeoxyglucose-positron emission tomography (FDG-PET)
- Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) performance scale (PS)
- Left ventricular ejection fraction (LVEF) \>= 50% on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO)
- Absolute neutrophil count (ANC) \>= 1,000/uL except in cases of marrow infiltration by lymphoma
- +13 more criteria
You may not qualify if:
- Contraindication to any of the individual components of glofitamab, tocilizumab or EPCH-R, including prior receipt of anthracyclines, or history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, or known sensitivity or allergy to murine products
- Prior systemic treatment for lymphoma with the exception of corticosteroids. Prior radiotherapy is allowed provided that this site is not used as a measurable site to assess response.
- Diagnosis of Burkitt lymphoma
- Prior organ transplantation
- Current Grade \> 1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease
- Prior systemic therapy for indolent lymphoma
- Prior use of any monoclonal antibody within 3 months of the start of cycle 1; any investigational therapy within 28 days prior to the start of cycle 1; vaccination with live vaccines within 28 days prior the start of cycle 1 and at any time during the study treatment period
- Prior therapy for large B-cell lymphoma except for patients who require lymphoma symptom control during screening may receive steroids in the following manner: Up to 30 mg/day of prednisone or equivalent may be used for lymphoma symptom control during screening, including prior to finalization of staging (not included as part of pre-phase treatment) If glucocorticoid treatment is urgently required at higher doses for lymphoma symptom control prior to the start of study treatment, tumor assessments must be completed prior to initiation of \> 30-100 mg/day of prednisone or equivalent. Prednisone \> 30-100 mg/day or equivalent may be given for a maximum of 7 days as a pre-phase treatment. If patients exceed the allowed dosing of corticosteroids, patients may still be eligible for the study provided that baseline imaging is performed (or repeated) after completion of the course of higher dose of steroids. Allowed corticosteroid dosing resets from the point of imaging forward and patients who do not exceed the allowed corticosteroid dosing from the point of imaging until initiation of study treatment may enroll
- History of other malignancy that could affect compliance with the protocol or interpretation of results except with permission of the principal investigator. The following are eligible without a specific waiver:
- Patients with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix at any time prior to the study are eligible
- Patients with any malignancy appropriately treated with curative intent and the malignancy has been in remission without treatment for \>= 2 years prior to enrollment are eligible
- Patients with low-grade, early-stage prostate cancer (Gleason score 6 or below, Stage 1 or 2) with no requirement for therapy at any time prior to study are eligible
- Evidence of significant, uncontrolled, concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina) or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
- Recent major surgery (within 4 weeks prior to the start of cycle 1), other than for diagnosis
- History or presence of an abnormal electrocardiogram (ECG) that is clinically significant in the investigator's opinion, including complete left bundle branch block, second- or third-degree heart block, or evidence of prior myocardial infarction
- +22 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Washingtonlead
- Genentech, Inc.collaborator
Study Sites (1)
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
Related Publications (2)
Roschewski M, Kurtz DM, Westin JR, Lynch RC, Gopal AK, Alig SK, Sworder BJ, Cherng HJ, Kuffer C, Blair D, Brown K, Goldstein JS, Schultz A, Close S, Chabon JJ, Diehn M, Wilson WH, Alizadeh AA. Remission Assessment by Circulating Tumor DNA in Large B-Cell Lymphoma. J Clin Oncol. 2025 Dec;43(34):3652-3661. doi: 10.1200/JCO-25-01534. Epub 2025 Aug 13.
PMID: 40802906DERIVEDLynch RC, Poh C, Ujjani CS, Warren EH, Smith SD, Shadman M, Morris K, Lee S, Rasmussen H, Ottemiller S, Shelby M, Keo S, Verni K, Kurtz DM, Alizadeh AA, Chabon JJ, Hogan GJ, Schulz A, Gooley T, Voutsinas JM, Gopal AK. Polatuzumab vedotin with infusional chemotherapy for untreated aggressive B-cell non-Hodgkin lymphomas. Blood Adv. 2023 Jun 13;7(11):2449-2458. doi: 10.1182/bloodadvances.2022009145.
PMID: 36521030DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Ryan Lynch
Fred Hutch/University of Washington Cancer Consortium
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 14, 2020
First Posted
January 18, 2020
Study Start
October 27, 2020
Primary Completion (Estimated)
December 1, 2026
Study Completion (Estimated)
December 1, 2031
Last Updated
March 3, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will not share