RECRUITING

Polatuzumab Vedotin and Combination Chemotherapy With or Without Glofitamab for the Treatment of Untreated Aggressive Large B-cell Lymphoma

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Conditions

Aggressive Non-Hodgkin LymphomaALK-Positive Large B-Cell LymphomaDiffuse Large B-Cell Lymphoma, Not Otherwise SpecifiedEBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise SpecifiedHigh Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 RearrangementsHigh Grade B-Cell Lymphoma, Not Otherwise SpecifiedPrimary Mediastinal Large B-Cell LymphomaT-Cell/Histiocyte-Rich Large B-Cell LymphomaGray-Zone Lymphoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2020-10-27
Study Completion:2031-12-01
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT04231877

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * 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:
  2. * High grade B-cell lymphoma with MYC and BCL2 and/or BCL6 translocations
  3. * High grade B-cell lymphoma, not otherwise specified (NOS)
  4. * Diffuse large B-cell lymphoma (DLBCL) NOS
  5. * Primary mediastinal B-cell lymphoma
  6. * T-cell/histiocyte-rich large-B-cell lymphoma
  7. * Epstein-Barr virus (EBV) + DLBCL, NOS
  8. * ALK+ large B-cell lymphoma (must be CD20+)
  9. * B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma
  10. * Be willing and able to provide written informed consent for the trial
  11. * Be \>= 18 years of age on day of signing informed consent
  12. * 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)
  13. * Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) performance scale (PS)
  14. * Left ventricular ejection fraction (LVEF) \>= 50% on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO)
  15. * Absolute neutrophil count (ANC) \>= 1,000/uL except in cases of marrow infiltration by lymphoma
  16. * Platelets \>= 75,000 / mcL except in cases of marrow infiltration by lymphoma or hypersplenism
  17. * Hemoglobin \>= 8 g/dL except in cases of marrow infiltration by lymphoma without red blood cell (RBC) transfusion within 14 days of first treatment
  18. * Measured or calculated creatinine clearance (Glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) \>= 40 mL/min.
  19. * 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)
  20. * Direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN
  21. * 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
  22. * 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
  23. * 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
  24. * 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
  25. * 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
  26. * 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
  27. * ARM B ONLY: Negative SARS-CoV-2 antigen or PCR test within 7 days prior to enrollment
  1. * 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
  2. * 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.
  3. * Richter's transformation from chronic lymphocytic leukemia/small lymphocytic lymphoma is not allowed. Transformation from follicular or other indolent lymphomas is allowed provided that the subject has not received prior systemic therapy for their lymphoma and the aggressive component meets one of the criteria listed in inclusion criterion 1
  4. * Diagnosis of Burkitt lymphoma
  5. * Prior organ transplantation
  6. * Current Grade \> 1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease
  7. * Prior systemic therapy for indolent lymphoma
  8. * 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
  9. * 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
  10. * 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:
  11. * 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
  12. * 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
  13. * 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
  14. * 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)
  15. * Recent major surgery (within 4 weeks prior to the start of cycle 1), other than for diagnosis
  16. * 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
  17. * 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
  18. * Positive test results for chronic hepatitis B infection (defined as positive hepatitis B surface antigen \[HBsAg\] serology):
  19. * Positive test results for hepatitis C (hepatitis C virus \[HCV\] antibody serology testing)
  20. * History of uncontrolled human immunodeficiency virus (HIV)
  21. * Patients with a history of progressive multifocal leukoencephalopathy
  22. * Pregnancy or lactation or intending to become pregnant during study
  23. * ARM B ONLY: Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
  24. * ARM B ONLY: Known or suspected chronic active Epstein-Barr virus infection
  25. * ARM B ONLY: Current or past history of Waldenström macroglobulinemia
  26. * ARM B ONLY: Current or past history of central nervous system (CNS) disease, such as stroke, epilepsy, CNS vasculitis, CNS lymphoma or neurodegenerative disease
  27. * ARM B ONLY: Participants with a history of stroke who have not experienced a stroke or transient ischemic attack in the past 2 years and have no residual neurological deficits, as judged by the investigator, are allowed
  28. * ARM B ONLY: Active autoimmune disease which is not well controlled by therapy
  29. * ARM B ONLY: Participants with a history of autoimmune-related hypothyroidism on a stable dose of thyroid-replacement hormone may be eligible
  30. * ARM B ONLY: Participants with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study
  31. * ARM B ONLY: Participants with active autoimmune disease with dermatologic manifestations are eligible for the study
  32. * 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
  33. * 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
  34. * ARM B ONLY: Clinically significant liver disease, including active viral or other hepatitis, current alcohol abuse, or cirrhosis
  35. * ARM B ONLY: Suspected active or latent tuberculosis (as confirmed by a positive interferon-gamma release assay)
  36. * ARM B ONLY: Grade 3 infection within 4 weeks of treatment initiation

Contacts and Locations

Study Contact

Ryan Lynch
CONTACT
206-606-1739
rclynch@uw.edu

Principal Investigator

Ryan Lynch
PRINCIPAL_INVESTIGATOR
Fred Hutch/University of Washington Cancer Consortium

Study Locations (Sites)

Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109
United States

Collaborators and Investigators

Sponsor: University of Washington

  • Ryan Lynch, PRINCIPAL_INVESTIGATOR, Fred Hutch/University of Washington Cancer Consortium

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-10-27
Study Completion Date2031-12-01

Study Record Updates

Study Start Date2020-10-27
Study Completion Date2031-12-01

Terms related to this study

Additional Relevant MeSH Terms

  • Aggressive Non-Hodgkin Lymphoma
  • ALK-Positive Large B-Cell Lymphoma
  • Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements
  • High Grade B-Cell Lymphoma, Not Otherwise Specified
  • Primary Mediastinal Large B-Cell Lymphoma
  • T-Cell/Histiocyte-Rich Large B-Cell Lymphoma
  • Gray-Zone Lymphoma