Polatuzumab Vedotin and Chemotherapy for Aggressive Large B-cell Lymphoma
This study is looking at the side effects of polatuzumab vedotin when given with combination chemotherapy, with or without glofitamab, for people with aggressive large B-cell lymphoma that hasn't been treated before. This type of lymphoma grows and spreads quickly. Polatuzumab vedotin is a treatment that targets specific cancer cells (CD79B positive) and delivers a medicine to kill them. Glofitamab is another treatment that may stop cancer cells from growing and spreading. The study aims to see how safe these treatments are. You may be eligible if you are 18 or older and have untreated aggressive B-cell large-B cell lymphoma with certain features. The study plans to enroll 56 participants, but its current status is unclear.
- Study design
- This is an interventional study with two arms. Participants receive different combinations of treatments.
- What's involved
- Participants will receive treatments intravenously (IV) and orally (PO) over cycles of 21 days for up to 6 cycles. They will also have various scans, biopsies, and blood tests throughout the study.
- Compensation
- Not stated in the trial record.
- Follow-up
- Adverse events will be measured for up to 30 days after the last dose of polatuzumab or first administration of alternate therapy.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT04231877
Polatuzumab Vedotin and Combination Chemotherapy With or Without Glofitamab for the Treatment of Untreated Aggressive Large B-cell Lymphoma
Active, Not Recruiting
PHASE1Ages 18+InterventionalTreatmentUniversity of WashingtonInvestigator-initiated
~56 participants
Updated 2026-08-21 on ClinicalTrials.gov
What's tested:Polatuzumab VedotinRituximabPrednisoneEtoposideDoxorubicinCyclophosphamide
At a glance
Recruiting sites
0 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Incidence of adverse events
Measured over Up to 30 days after last dose of polatuzumab or first administration of alternate therapy
Conditions
Where it's being run
1 sites across 1 statesWashington1
Study leadership
- Ryan Lynch · PRINCIPAL_INVESTIGATOR · Fred Hutch/University of Washington Cancer Consortium
Who to contact
This trial hasn't published a contact. View it on ClinicalTrials.gov
Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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
Platelets \>= 75,000 / mcL except in cases of marrow infiltration by lymphoma or hypersplenism
Hemoglobin \>= 8 g/dL except in cases of marrow infiltration by lymphoma without red blood cell (RBC) transfusion within 14 days of first treatment
Measured or calculated creatinine clearance (Glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) \>= 40 mL/min.
Serum total bilirubin =\< 1.5 X upper limit of normal (ULN) (Patients with documented Gilbert disease may be enrolled if total bilirubin =\< 3.0 x ULN)
Direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X ULN OR =\< 5 X ULN for subjects with liver involvement
International Normalized Ratio (INR) or Prothrombin Time (PT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
Activated partial thromboplastin time (aPTT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants, or subject is shown to have an antiphospholipid antibody on workup
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of =\< 1% per year during the treatment period and for at least 12 months after the last dose of EPCH-R, 9 months after the last dose of polatuzumab, 2 months after the last dose of glofitamab (Arm B participants), or 3 months after the last dose of tocilizumab (if applicable), whichever is longer. Women must refrain from donating eggs during this same period. A woman is considered to be of childbearing potential if she is post-menarcheal, has not reached a postmenopausal state (=\<12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements. Examples of contraceptive methods with a failure rate of =\<1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception
For women of childbearing potential, a negative serum pregnancy test result during screening period. Women who are considered not to be of childbearing potential are not required to have a pregnancy test
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below: With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 6 months after the last dose of EPCH-R or polatuzumab, 2 months after the last dose of glofitamab (Arm B participants), or 2 months after the last dose of tocilizumab (if applicable), whichever is longer. Men must refrain from donating sperm during this same period. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of preventing drug exposure. Male patients considering preservation of fertility should bank sperm before study treatment
ARM B ONLY: Negative SARS-CoV-2 antigen or PCR test within 7 days prior to enrollment
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
Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) which requires systemic treatment. Patients may proceed with screening during treatment for infection, but systemic treatment must be completed by cycle 1 day 1
Positive test results for chronic hepatitis B infection (defined as positive hepatitis B surface antigen \[HBsAg\] serology):
Positive test results for hepatitis C (hepatitis C virus \[HCV\] antibody serology testing)
History of uncontrolled human immunodeficiency virus (HIV)
Patients with a history of progressive multifocal leukoencephalopathy
Pregnancy or lactation or intending to become pregnant during study
ARM B ONLY: Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
ARM B ONLY: Known or suspected chronic active Epstein-Barr virus infection
ARM B ONLY: Current or past history of Waldenström macroglobulinemia
ARM B ONLY: Current or past history of central nervous system (CNS) disease, such as stroke, epilepsy, CNS vasculitis, CNS lymphoma or neurodegenerative disease
ARM B ONLY: Active autoimmune disease which is not well controlled by therapy
ARM B ONLY: Participants with a history of autoimmune-related hypothyroidism on a stable dose of thyroid-replacement hormone may be eligible
ARM B ONLY: Participants with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study
ARM B ONLY: Participants with active autoimmune disease with dermatologic manifestations are eligible for the study
ARM B ONLY: Participants with a history of autoimmune hepatitis, systemic lupus erythematosus, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener granulomatosis, Sjögren syndrome, multiple sclerosis, or glomerulonephritis will be excluded
ARM B ONLY: Participants with a history of immune thrombocytopenic purpura, autoimmune hemolytic anemia, Guillain-Barré syndrome, myasthenia gravis, myositis, rheumatoid arthritis, vasculitis, or other autoimmune disease will be excluded unless they have not required systemic therapy in the last 12 months
ARM B ONLY: Clinically significant liver disease, including active viral or other hepatitis, current alcohol abuse, or cirrhosis
ARM B ONLY: Suspected active or latent tuberculosis (as confirmed by a positive interferon-gamma release assay)
ARM B ONLY: Grade 3 infection within 4 weeks of treatment initiation
Exclusion
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.
What this trial measures
- Incidence of adverse eventsUp to 30 days after last dose of polatuzumab or first administration of alternate therapy
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.