Polatuzumab Vedotin + Chemotherapy for Large B-Cell Lymphoma
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: University of Washington
Must not be taking: Monoclonal antibodies, Investigational therapy
Disqualifiers: Burkitt lymphoma, Organ transplant, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?
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.
Do I need to stop my current medications for the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that prior systemic treatment for lymphoma is not allowed, except for corticosteroids under certain conditions. It's best to discuss your current medications with the trial team to get specific guidance.
What data supports the effectiveness of the drug combination Polatuzumab Vedotin + Chemotherapy for Large B-Cell Lymphoma?
Is the combination of Polatuzumab Vedotin and chemotherapy safe for treating large B-cell lymphoma?
The combination of drugs similar to those in Polatuzumab Vedotin treatment, such as doxorubicin, cyclophosphamide, and rituximab, has been studied for safety in various lymphomas. These studies show that while these drugs can cause side effects like myelosuppression (reduced blood cell production), cardiotoxicity (heart damage), and nausea, they are generally considered safe when used under medical supervision.678910
How is the drug Polatuzumab Vedotin + Chemotherapy unique for treating large B-cell lymphoma?
This treatment combines Polatuzumab Vedotin, a targeted therapy that delivers a toxic agent directly to cancer cells, with a chemotherapy regimen including drugs like cyclophosphamide and doxorubicin, which are known to be effective in treating lymphomas. The combination aims to enhance the effectiveness of standard chemotherapy by adding a targeted approach, potentially improving outcomes for patients with large B-cell lymphoma.1112131415
Eligibility Criteria
This trial is for adults with untreated aggressive large B-cell lymphoma. Participants must have proper kidney and liver function, no severe allergies to monoclonal antibodies or chemotherapy components, and agree to use effective contraception. Those with prior systemic treatment for lymphoma (except corticosteroids), certain other health conditions, or who are pregnant cannot join.Inclusion Criteria
Hemoglobin >= 8 g/dL
aPTT within specified limits
ANC >= 1,000/uL
See 16 more
Exclusion Criteria
Pregnancy, lactation, or intent to become pregnant
My CLL/SLL has transformed into a more aggressive form.
I have had cancer before, but it might not affect my eligibility.
See 14 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Treatment
Participants receive rituximab, polatuzumab vedotin, prednisone, etoposide, doxorubicin, and cyclophosphamide with or without glofitamab for up to 6 cycles
18 weeks
6 cycles, each 21 days apart
Follow-up
Participants are monitored for safety and effectiveness after treatment
5 years
Periodic visits
Treatment Details
Interventions
- Cyclophosphamide (Alkylating agents)
- Doxorubicin (Anti-tumor antibiotic)
- Etoposide (Topoisomerase I inhibitors)
- Polatuzumab Vedotin (Monoclonal Antibodies)
- Prednisone (Corticosteroid)
- Rituximab (Monoclonal Antibodies)
Trial OverviewThe trial tests polatuzumab vedotin combined with chemotherapy drugs like cyclophosphamide, doxorubicin, etoposide, prednisone, rituximab against aggressive large B-cell lymphoma. Polatuzumab vedotin targets cancer cells specifically to deliver a toxic agent that kills them.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Arm B (polatuzumab vedotin, glofitamab, chemotherapy)Experimental Treatment14 Interventions
Patients 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.
Group II: Arm A (polatuzumab vedotin, chemotherapy) [CLOSED TO ACCRUAL 05/23/2024]Experimental Treatment13 Interventions
Patients 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.
Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:
🇺🇸 Approved in United States as Cytoxan for:
- Breast cancer
- Ovarian cancer
- Multiple myeloma
- Leukemia
- Lymphoma
- Rheumatoid arthritis
🇪🇺 Approved in European Union as Endoxan for:
- Breast cancer
- Ovarian cancer
- Multiple myeloma
- Leukemia
- Lymphoma
- Rheumatoid arthritis
🇨🇦 Approved in Canada as Neosar for:
- Breast cancer
- Ovarian cancer
- Multiple myeloma
- Leukemia
- Lymphoma
- Rheumatoid arthritis
🇯🇵 Approved in Japan as Endoxan for:
- Breast cancer
- Ovarian cancer
- Multiple myeloma
- Leukemia
- Lymphoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Fred Hutch/University of Washington Cancer ConsortiumSeattle, WA
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Who Is Running the Clinical Trial?
University of WashingtonLead Sponsor
Genentech, Inc.Industry Sponsor
References
A Cancer and Leukemia Group B multi-center study of DA-EPOCH-rituximab in untreated diffuse large B-cell lymphoma with analysis of outcome by molecular subtype. [2022]A phase II trial of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (DA-EPOCH-R) from the National Cancer Institute showed promising activity in untreated diffuse large B-cell lymphoma. The Cancer and Leukemia Group B conducted a study to determine if these results could be reproduced in a multi-institutional setting.
Two-weekly dose-adjusted (DA)-EPOCH-like chemotherapy with high-dose dexamethasone plus rituximab (DA-EDOCH14-R) in poor-prognostic untreated diffuse large B-cell lymphoma. [2015]The activity and safety of two-weekly dose-adjusted (DA)-EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin)-like chemotherapy with high-dose dexamethasone plus rituximab (DA-EDOCH14-R) was explored in 20 patients with previously untreated poor prognosis diffuse large B-cell lymphoma (DLBCL). The main outcomes were compared with those of 27 poor-prognosis patients enrolled into a previous trial of 3-weekly DA-EPOCH-R. Toxicity was manageable and there were no therapy-related deaths. Three-year progression-free survival (PFS) was superior in the DA-EDOCH14-R group (95% vs. 74%, P = 0·08). Importantly, this improvement in PFS with the two-weekly DA-EDOCH14-R was particularly notable in patients with an age-adjusted International Prognostic Index of 3 (100% vs. 30%, P
Chemotherapy for non-Hodgkin lymphoma in the hemodialysis patient: A comprehensive review. [2021]Chemotherapy for non-Hodgkin lymphoma (NHL) in the hemodialysis (HD) patient is a challenging situation. Because many drugs are predominantly eliminated by the kidneys, chemotherapy in the HD patient requires special considerations concerning dose adjustments to avoid overdose and toxicities. Conversely, some drugs are removed by HD and may expose the patient to undertreatment, therefore the timing of drug administration in relation to HD sessions must be carefully planned. Also, the metabolites of some drugs show different toxicities and dialysability as compared with the parent drug, therefore this must also be catered for. However, the pharmacokinetics of many chemotherapeutics and their metabolites in HD patients are unknown, and the fact that NHL patients are often treated with distinct multiagent chemotherapy regimens makes the situation more complicated. In a realm where uncertainty prevails, case reports and case series reporting on actual treatment and outcomes are extremely valuable and can aid physicians in decision making from drug selection to dosing. We carried out an exhaustive review of the literature and adopted 48 manuscripts consisting of 66 HD patients undergoing 71 chemotherapy regimens for NHL, summarized the data, and provide recommendations concerning dose adjustments and timing of administration for individual chemotherapeutics where possible. The chemotherapy regimens studied in this review include, but are not limited to, rituximab, cyclophosphamide + vincristine + prednisolone (CVP) and cyclophosphamide + doxorubicin + vincristine + prednisolone (CHOP)-like regimens, chlorambucil, ibrutinib, bendamustine, methotrexate, platinum compounds, cytarabine, gemcitabine, etoposide, ifosfamide, melphalan, busulfan, fludarabine, mogamulizumab, brentuximab vedotin, and 90 Y-ibritumomab tiuxetan.
Clinical experience with biweekly CHOP plus rituximab chemoimmunotherapy for the treatment of aggressive B-cell non-Hodgkin lymphoma. [2021]The results of CHOP-21 (cyclophosphamide, doxorubicin, vincristine and prednisone given every 21 days) for the treatment of aggressive B-cell lymphoma have recently been improved by the addition of rituximab and by increasing the dose density. R-CHOP-14 combines these two approaches.
Pooled analysis of AIDS malignancy consortium trials evaluating rituximab plus CHOP or infusional EPOCH chemotherapy in HIV-associated non-Hodgkin lymphoma. [2022]Improved outcomes have recently been reported for rituximab (R) plus rituximab plus infusional etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH) chemotherapy in patients with human immunodeficiency virus (HIV)-associated, aggressive B-cell, non-Hodgkin lymphoma (NHL). The objective of the current analysis was to assess whether patient selection or other factors contributed to this improvement and to identify patients who are at the greatest risk for lethal toxicity.
Efficacy and safety of front-line treatments for advanced Hodgkin lymphoma: a systematic literature review. [2021]To assess evidence on the safety and efficacy of ABVD (doxorubicin [Adriamycin®], bleomycin, vinblastine, and dacarbazine), BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), and A+AVD (brentuximab vedotin, with doxorubicin, vinblastine, and dacarbazine) for advanced-stage Hodgkin lymphoma (HL).
CEOP-B alternated with VIMB in intermediate-grade and high-grade non-Hodgkin's lymphoma: a pilot study. [2017]To improve response and toxicity in treatment of non-Hodgkin's lymphomas (NHLs), a prospective single-arm trial was initiated using cyclophosphamide, epirubicin, vincristine, prednisone, and bleomycin (CEOP-B) alternated with etoposide (VP-16), ifosfamide, mitoxantrone, and bleomycin (VIMB).
Comparison of the adverse event profiles of conventional and liposomal formulations of doxorubicin using the FDA adverse event reporting system. [2022]Doxorubicin (DOX) is an anthracycline widely used for the treatment of solid and hematological tumors. The aim of this study was to assess the adverse event profiles of conventional DOX and liposomal DOX. This is the first study to evaluate the effect of a liposomal formulation of DOX using spontaneous reporting system (SRS) databases. The SRS used was the US Food and Drug Administration Adverse Event Reporting System (FAERS). This study relied on definitions of preferred terms provided by the Medical Dictionary for Regulatory Activities (MedDRA) and the standardized MedDRA Queries (SMQ) database. We also calculated the reporting odds ratios (RORs) of suspected drugs (conventional DOX; PEGylated-liposome DOX; non-PEGylated-liposome DOX). The FAERS database contained 7,561,254 reports from January 2004 to December 2015. The number of reported AE cases for conventional DOX, PEGylated-liposome DOX, and non-PEGylated-liposome DOX was 5039, 3780, and 349, respectively. Conventional DOX and liposomal DOX have potential risks of causing myelosuppression, cardiotoxicity, alopecia, nausea, and vomiting, among other effects. The RORs (95% CI) from SMQ for haematopoietic leucopenia associated with conventional DOX, PEGylated-liposome DOX, and non-PEGylated-liposome DOX were 12.75 (11.89-13.68), 6.43 (5.81-7.13), and 14.73 (11.42-18.99), respectively. Liposomal DOX formulations were associated with lower RORs with regard to myelosuppression, cardiotoxicity, and alopecia than the conventional DOX was. The RORs (95% CI) for palmar-plantar erythrodysesthesia (PPE) associated with conventional DOX, PEGylated-liposome DOX, and non-PEGylated-liposome DOX were 6.56 (4.74-9.07), 64.77 (56.84-73.80), and 28.76 (15.77-52.45), respectively. This study is the first to evaluate the relationship between DOX liposomal formulations and their adverse event profiles. The results indicate that careful observation for PPE is recommended with the use of liposomal DOX, especially PEGylated-liposome DOX formulations.
A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma. [2021]Rituximab in combination with chemotherapy has shown efficacy in patients with diffuse large B-cell lymphoma (DLBCL) for more than 15 years. HLX01 was developed as the rituximab biosimilar following a stepwise approach to demonstrate biosimilarity in analytical, pre-clinical, and clinical investigations to reference rituximab. With demonstrated pharmacokinetic similarity, a phase 3 multi-center, randomized, parallel, double-blind study (HLX01-NHL03) was subsequently conducted to compare efficacy and safety between HLX01 plus cyclophosphamide, doxorubicin, vincristine, and prednisone (H-CHOP) and reference rituximab plus CHOP (R-CHOP) in a total of 407 treatment-naïve, CD20-positive DLBCL patients aged 18-80 years. The primary efficacy endpoint was best overall response rate (ORR) within six cycles of treatment in the per-protocol set (PPS). Secondary endpoints included 1-year efficacy outcomes, safety, and immunogenicity profile. The results showed difference in ORRs [H-CHOP 94.1%; R-CHOP 92.8%] between two treatment groups was 1.4% (95% confidence interval [CI], - 3.59 to 6.32, p = 0.608) which falls within the pre-defined equivalence margin of ± 12%. The safety profile was comparable between the treatment groups, with a similar overall incidence of treatment-emergent adverse events (H-CHOP 99.5%, R-CHOP 99.0%, p = 1.000) and serious adverse events (H-CHOP 34.0%, R-CHOP 32.5%, p = 0.752). This study established bioequivalence in efficacy and safety between HLX01 and reference rituximab. The trial was registered at http://www.chinadrugtrials.org.cn on 26 August 2015 [#CTR20150583].
Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. [2022]To determine the safety and efficacy of the combination of the chimeric anti-CD20 antibody, Rituxan (Rituximab, IDEC-C2B8; IDEC Pharmaceuticals Corporation, San Diego, CA), and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy.
VP-16-213 in the treatment of stage III and IV diffuse lymphocytic lymphoma of the large cell (histiocytic) variety: an interim report. [2013]A pilot study has previously demonstrated antitumor activity for the epipodophyllotoxin VP-16-213 in patients with diffuse lymphocytic lymphoma of the large cell (histiocytic) variety. To define this observation further, a prospective randomized trial was undertaken in patients with stage III and IV disease, comparing this agent used alone (group 1, 41 patients) to the response obtained when the same schedule of VP-16-213 was combined with either cyclophosphamide (group 2, 36 patients) or doxorubicin (group 3, 41 patients). The quantity of VP-16-213 given to patients in the three groups was equivalent. Of these 118 patients, three were lost to followup and thus were excluded from further study. Specifically included were 12 patients who died within 1 month of diagnosis while still receiving induction chemotherapy. For the three groups, complete remission rates were 39%, 26%, and 54%, and additional partial remissions were obtained in 20%, 11%, and 10% of the patients, respectively. The lower remission rates obtained in patients receiving cyclophosphamide combined with VP-16-213 are statistically significant (P less than 0.05), but no explanation for this is evident since the distribution of poor prognostic factors among the three groups was uniform. The higher percent of complete remission and the greater number of patients remaining free from disease in group 3 demonstrate the superiority of the combination of VP-16-213 with the anthracycline antibiotic doxorubicin.
Novel CD20 monoclonal antibodies for lymphoma therapy. [2022]Rituximab (RTX), a monoclonal antibody (mAb) against CD20, has been widely used for lymphoma therapy. RTX in combination with cyclophosphamide /doxorubicin /vincristine /prednisone (R-CHOP) remains the standard frontline regimen for diffuse large B-cell lymphoma. However, suboptimal response and /or resistance to rituximab have remained a challenge in the therapy of B-cell non-Hodgkin's lymphoma (NHL). Novel agents are under active clinical trials. This review will summarize the latest development in new mAbs against CD20, which include second-generation mAbs, ofatumumab, veltuzumab (IMMU-106), ocrelizumab (PRO70769), and third-generation mAbs, AME-133v (ocaratuzumab), PRO131921 and GA101 (obinutumumab).
Phase II study of paclitaxel in combination with mitoxantrone and ifosfamide/mesna for patients with relapsed or refractory non-Hodgkin's lymphoma after failure to cytarabine/cisplatin combination. [2019]Evaluate response, duration of response, and toxicity of paclitaxel in combination with other drugs known to be effective in non-Hodgkin's lymphoma (NHL).
Unfavorable histologies of non-Hodgkin's lymphoma treated with ProMACE-CytaBOM: a groupwide Southwest Oncology Group study. [2017]Chemotherapy using cyclophosphamide, doxorubicin, etoposide, cytarabine, bleomycin, vincristine, methotrexate with leucovorin, and prednisone (ProMACE-CytoBOM) for patients with intermediate- and high-grade non-Hodgkin's lymphomas was tested by the Southwest Oncology Group (SWOG) to confirm the activity of the regimen and to test the feasibility and safety of administering third-generation drug regimens in a cooperative group setting. On day 1, cyclophosphamide, doxorubicin, and etoposide were administered, followed by cytarabine, bleomycin, vincristine and methotrexate with leucovorin given on day 8. There were 51 complete remissions (CRs) among 78 previously untreated patients (65%) having clinical stage II-IV disease. The median length of follow-up is 37.9 months with 57% of patients alive at 3 years and 50% of CR patients free of disease at 3 years. Patients with diffuse large-cell lymphoma have the best survival (63% at 3 years) and relapse-free survival (RFS; 68% at 3 years with no relapses seen after 14 months). Administration of ProMACE-CytoBOM is feasible and safe in a cooperative group setting with 84% of 537 courses of treatment given exactly according to schedule and fatal toxicities seen in five patients (6%). ProMACE-CytaBOM may represent improved treatment for diffuse large-cell lymphoma, but the modest differences compared with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) indicate the need for a prospective randomized comparative trial.
Evolving role of rituximab in the treatment of patients with non-Hodgkin's lymphoma. [2015]Rituximab is the first monoclonal antibody to have been registered for the treatment of B-cell lymphomas. Randomized studies have demonstrated its activity in follicular lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma in untreated or relapsing patients. Rituximab has transformed the outcome of these patients because of its high activity and low toxicity. A combination of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, has the highest efficacy ever described with any chemotherapy in diffuse large B-cell lymphoma and follicular lymphoma.