Epcoritamab + Rituximab for Follicular Lymphoma
Recruiting in Palo Alto (17 mi)
+3 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Reid Merryman, MD
Must not be taking: Immunosuppressants, Corticosteroids
Disqualifiers: Autoimmune disease, Heart failure, HIV, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?The purpose of this study is to determine how effective and safe the combination of rituximab and epcoritamab is in treating patients with Follicular Lymphoma (FL) and who have not received other treatments for their lymphoma.
The names of the study drugs involved in this study are:
* Rituximab (a type of monoclonal antibody therapy)
* Epcoritamab (a T-cell bispecific antibody)
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, if you are on systemic immunosuppressive therapy or taking more than 10 mg of prednisone daily, you may not be eligible to participate.
What data supports the effectiveness of the drug combination Epcoritamab and Rituximab for treating follicular lymphoma?
Rituximab, a key component of the treatment, has been shown to improve survival rates and increase the time patients live without their disease getting worse when combined with chemotherapy for follicular lymphoma. This suggests that combining Rituximab with other drugs, like Epcoritamab, could potentially enhance treatment effectiveness.
12345Is the combination of Epcoritamab and Rituximab safe for treating follicular lymphoma?
Rituximab has been used for many years in treating follicular lymphoma and is generally considered safe, though it can cause mild side effects like fever and chills, especially during the first infusion. Serious side effects are rare, but new safety alerts can arise, so it's important for doctors to monitor patients closely.
678910What makes the drug combination of Epcoritamab and Rituximab unique for treating follicular lymphoma?
The combination of Epcoritamab and Rituximab is unique because it pairs a novel bispecific antibody (Epcoritamab) that targets both CD3 and CD20 proteins on immune cells, with Rituximab, a well-established anti-CD20 antibody. This dual-targeting approach may enhance the immune system's ability to attack lymphoma cells more effectively than traditional treatments.
35111213Eligibility Criteria
Adults with untreated Follicular Lymphoma (FL) who are not in urgent need of chemotherapy can join this trial. They must have good organ function, no prior systemic therapy for FL except radiation or short steroids, and agree to use effective contraception. Exclusions include recent major surgery, active infections like hepatitis B/C or HIV, severe medical conditions affecting study participation, certain heart issues within the last 6 months, pregnancy, breastfeeding intentions during the study period.Inclusion Criteria
Examples of contraceptive methods with a failure rate of <1% per year.
I have not had any drug treatments for follicular lymphoma, but I may have had radiation or steroids.
Willingness to remain abstinent or to use two effective contraceptive methods.
+7 more
Exclusion Criteria
I have severe heart failure or my heart pumps less blood than normal.
I have not had major surgery or significant injury in the last 4 weeks.
I do not have any severe or uncontrolled medical conditions.
+23 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive Rituximab and Epcoritamab. Cycle 1 includes Rituximab on Days -14, -7, 1, 8 and Epcoritamab on Days 1, 8, 15, 22 of a 6-week cycle. Cycles 2-3 include Epcoritamab on Days 1, 8, 15, 22 of a 4-week cycle. Cycles 4-9 include Epcoritamab on Days 1 and 15 of a 4-week cycle.
9-10 months
Multiple visits per cycle for drug administration and evaluations
Follow-up
Participants are monitored for safety and effectiveness after treatment, with surveillance imaging at months 13, 18, and 24, and follow-up visits for up to 5 years.
5 years
Long-term follow-up
Participants are monitored for long-term outcomes, including overall survival and incidence of histological transformation, for up to 10 years.
10 years
Participant Groups
The trial is testing a combination of two drugs: Rituximab (a monoclonal antibody) and Epcoritamab (a T-cell bispecific antibody), to see how safe and effective they are together as a first-line treatment for patients with Follicular Lymphoma who haven't been treated before.
1Treatment groups
Experimental Treatment
Group I: Epcoritamab + RituximabExperimental Treatment2 Interventions
Participants will undergo study procedures as outlined:
* PET/CT scans at baseline and after cycles 2, 5, and 9 of treatment.
* Cycle 1:
* Days -14, -7, 1, 8 of 6 week cycle: Predetermined dose of Rituximab.
* Days 1, 8, 15, 22 of 6 week cycle: Predetermined dose of Epcoritamab. (Day 15 of Epcoritamab dosage will be administered in the hospital.)
* Cycles 2 - 3:
--Days 1, 8, 15, 22 of 4 week cycle: Predetermined dose of Epcoritamab.
* Cycles 4 - 9:
* Day 1 of 4 week cycle: Predetermined dose of Epcoritamab.
* Day 15 of 4 week cycle: Predetermined dose of Epcoritamab.
* Surveillance imaging (PT/CT scans) at months 13, 18, and 24 after initiation of treatment.
* Follow up visits for up to 5 years.
Epcoritamab is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Epkinly for:
- Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy
- Diffuse large B-cell lymphoma after two or more lines of systemic therapy
🇪🇺 Approved in European Union as Tepkinly for:
- Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy
- Relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Rochester Medical CenterRochester, NY
The Ohio State University Wexner Medical CenterColumbus, OH
Medical College of WisconsinMilwaukee, WI
Dana-Farber Cancer InstituteBoston, MA
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Who Is Running the Clinical Trial?
Reid Merryman, MDLead Sponsor
AbbVieIndustry Sponsor
GenmabIndustry Sponsor
References
Use of rituximab in patients with follicular lymphoma. [2019]Advanced stage symptomatic follicular non-Hodgkin's lymphoma (NHL) is rarely, if ever, curable with conventional chemotherapy. Patients classically experience a pattern of remission and relapse, eventually dying of their disease. Data from a number of large-scale randomised phase III trials, both as first-line therapy and in relapsed/refractory patients, comparing rituximab plus chemotherapy with chemotherapy alone indicate that the addition of rituximab to a number of different chemotherapy regimens increases response rates and progression-free survival (PFS), without significantly increasing toxicity. Moreover, in four trials, three in first-line and one in relapsed disease, a significant overall survival benefit has been observed for rituximab combination therapy. These data indicate that patients with follicular NHL who require therapy should now receive rituximab plus chemotherapy as first-line treatment. Additionally, a strong case remains for offering rituximab-based therapy to patients with relapsed disease who have not previously received it, and in those who have previously responded well to this agent. Rituximab maintenance therapy has also been shown to significantly prolong PFS after rituximab in combination with chemotherapy in patients with relapsed disease and in newly diagnosed patients who have not received rituximab during induction, and the benefit of maintenance after immunochemotherapy in relapsed patients may yet be mirrored by ongoing studies in the first-line setting. This overview considers the most recently published clinical trials of rituximab and their potential effect on clinical practice in the treatment of follicular NHL.
How have outcomes for patients with follicular lymphoma changed with the addition of monoclonal antibodies? [2019]The outcome for patients with follicular lymphoma (FL) has substantially improved over the last few years. This improved survival appears to be largely related to the increasingly widespread use of anti-CD20 monoclonal antibody (mAb) rituximab in the therapy of FL today, either in combination with chemotherapy, for remission 'induction' and more recently as 'maintenance' therapy. Encouraging results have also been reported from radiolabelled anti-CD20 mAb or radioimmunotherapy (RIT), which exploits the unique method of action of this approach and high radiosensitivity of FL. High response rates and durable remissions have been seen with both (90)Y Ibritumomab tiuxetan and (131)I Tositumomab, and more recently compelling data are emerging demonstrating the efficacy of using these drugs as consolidation after initial treatment with chemotherapy or rituximab plus chemotherapy combinations. This review will focus on the current approaches and explore the data that has led to the emergence of a new nomenclature appearing in the language of clinicians involved in the treatment of FL, namely 'induction' therapy, 'consolidation' of initial response and 'maintenance' therapy. The current treatment approaches that have led to such increased optimism regarding the therapeutic outcome in FL are evaluated and discussed.
Biological therapy doublets: pairing rituximab with interferon, lenalidomide, and other biological agents in patients with follicular lymphoma. [2021]Rituximab (R) is a monoclonal antibody with high therapeutic efficacy in low-grade CD20+ lymphoma. The combination of R with chemotherapy is the most common treatment option for patients with follicular lymphoma (FL). The efficacy of R has also been shown to be augmented, when used in combinations with biologicals such as interferon-alpha-2a (IFN), bortezomib, or lenalidomide. The best combination of these drugs are not well defined and a better understanding of pharmacokinetics and timing of drugs relative to the rituximab infusion is crucial. Other new targeted agents, such as inhibitors of BTK and PI3Kdelta, have also been promising in FL. Translational research questions should be added to clinical trial protocols to increase the knowledge on how the tumor microenvironment and the host immune system affect the response to the different drugs and combinations with the aim of a more individualized therapy.
Phase II trial of short-course CHOP-R followed by 90Y-ibritumomab tiuxetan and extended rituximab in previously untreated follicular lymphoma. [2016]Radioimmunotherapy has been approved for relapsed follicular lymphoma (FL), including rituximab-refractory FL. This study was designed to determine the CR rate with short-course chemoimmunotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (CHOP-R) followed by 90-Y ibritumomab tiuxetan (RIT) with extended rituximab as first-line treatment.
[Therapy of follicular lymphoma]. [2018]The treatment options for patients with follicular lymphoma have substantially improved in the last years, in particular with the development of innovative, antibody-based therapeutic strategies. Thus, the anti-CD20 antibody rituximab is one of the cornerstones in the therapy of follicular lymphoma today. It is used in combination with chemotherapy or as a single agent therapy for remission induction and as maintenance therapy. Encouraging results were also reported from monoclonal anti-CD20 antibodies, which are conjugated to radionuclides and exploit the high radiosensitivity of lymphomas. An example for this is the anti-CD20 antibody ibritumomab tiuxetan, which is coupled to 90Yttrium and shows comparable activity to rituximab. Current trials are underway testing whether, for example, the sequential application of a rituximab/chemotherapy induction, myeloablative consolidation therapy followed by autologous stem cell transplantation and rituximab maintenance further improves the therapeutic outcome in follicular lymphoma, or even has curative potential in a subgroup of patients with this disease.
Critical appraisal of rituximab in the maintenance treatment of advanced follicular lymphoma. [2022]Rituximab is an IgG1, chimeric monoclonal antibody specifically designed to recognize the CD20 antigen expressed on the surface of normal and malignant B-lymphocytes, from the B-cell precursor to the mature B-cells of the germinal center, and by most neoplasms derived from B-cells. After 2 decades of use, rituximab is firmly positioned in the treatment of follicular lymphoma (FL), both in the front line and in the relapsing disease, improving previous results by including it in classical chemotherapy regimens. However, the pharmacology of rituximab continues to generate controversial issues especially regarding the mechanisms of action in vivo. The contribution of rituximab as a maintenance treatment in FL has been significant progress in the management of this disease without an increase in side effects or a decrease in the quality of life of patients. With the widespread use of rituximab, there are new security alerts and side effects not previously detected in the pivotal trials that clinicians should learn to recognize and manage. In this article, we will review the pharmacokinetics and pharmacodynamics of rituximab, the management issues in the treatment of advanced FL focusing on maintenance rituximab, its long-term efficacy and safety profile, and its effect on the quality of life.
Phase 2 multicentre study of single-agent ofatumumab in previously untreated follicular lymphoma: CALGB 50901 (Alliance). [2021]Rituximab monotherapy has proven efficacy in treatment-naïve, asymptomatic advanced-stage follicular lymphoma (FL). Ofatumumab is a fully humanized anti-CD20 monoclonal antibody with increased CD20 affinity and complement-dependent cytotoxicity. This phase 2 trial (NCT01190449) evaluated ofatumumab in patients with untreated, low/intermediate-risk FL International Prognostic Index (FLIPI), advanced-stage FL to determine single-agent efficacy. Patients with measurable disease in stages III/IV or bulky stage II, regardless of Groupe d'Etude des Lymphomes Folliculaires criteria, received 4 weekly 1000 mg doses followed by four extended induction doses once every 8 weeks. Primary endpoint was overall response rate (ORR) to 1000 mg; secondary endpoints were progression-free survival (PFS) and safety. Fifty-one patients were enrolled. Fifteen patients were randomized to 500 mg prior to discontinuing that arm for slow accrual. Among 36 patients on the 1000 mg arm, ORR was 84%, median PFS was 1·9 years and median response duration was 23·7 months. All patients remain alive. No grade 4 infusion reactions or grade 3/4 infections occurred. Grade 3 infusion reactions occurred in 25% in the 1000 mg arm only (all first infusion); all but two patients continued on study. Discontinuation was 6% for the total study population. Ofatumumab monotherapy administered by extended induction in untreated, low/intermediate-risk FLIPI, advanced-stage FL is well tolerated and active. Activity appears similar to that reported with single-agent rituximab.
Efficacy and safety of new anti-CD20 monoclonal antibodies versus rituximab for induction therapy of CD20+ B-cell non-Hodgkin lymphomas: a systematic review and meta-analysis. [2023]Rituximab combined with chemotherapy is the first-line induction therapy of CD20 positive B-cell non-Hodgkin lymphomas (CD20+ B-NHL). Recently new anti-CD20 monoclonal antibodies (mAbs) have been developed, but their efficacy and safety compared with rituximab are still controversial. We searched MEDLINE, Embase, and Cochrane Library for eligible randomized controlled trials (RCTs) that compared new anti-CD20 mAbs with rituximab in induction therapy of B-NHL. The primary outcomes are progression-free survival (PFS) and overall survival (OS), additional outcomes include event-free survival (EFS), disease-free survival (DFS), overall response rate (ORR), complete response rate (CRR) and incidences of adverse events (AEs). Time-to-event data were pooled as hazard ratios (HRs) using the generic inverse-variance method and dichotomous outcomes were pooled as odds ratios (ORs) using the Mantel-Haenszel method with their respective 95% confidence interval (CI). Eleven RCTs comprising 5261 patients with CD20+ B-NHL were included. Compared with rituximab, obinutuzumab significantly prolonged PFS (HR 0.84, 95% CI 0.73-0.96, P = 0.01), had no improvement on OS, ORR, and CRR, but increased the incidences of serious AEs (OR 1.29, 95% CI 1.13-1.48, P < 0.001). Ofatumumab was inferior to rituximab in consideration of ORR (OR 0.73, 95% CI 0.55-0.96, P = 0.02), and had no significant differences with rituximab in regard to PFS, OS and CRR. 131I-tositumomab yielded similar PFS, OS, ORR and CRR with rituximab. 90Y-ibritumomab tiuxetan increased ORR (OR 3.07, 95% CI 1.47-6.43, P = 0.003), but did not improve PFS, DFS, OS and CRR compared with rituximab. In conclusion, compared with rituximab in induction therapy of CD20+ B-NHL, obinutuzumab significantly improves PFS but with higher incidence of AEs, ofatumumab decreases ORR, 90Y-ibritumomab tiuxetan increases ORR.
The combination of ibrutinib and rituximab demonstrates activity in first-line follicular lymphoma. [2021]This phase 2 study evaluated the activity and safety of ibrutinib, a Bruton's tyrosine kinase inhibitor, plus rituximab in adults with previously untreated follicular lymphoma. Patients received once-daily ibrutinib 560 mg continuously plus once-weekly rituximab 375 mg/m2 for 4 weeks beginning Week 1 (Arm 1, n = 60) or Week 9 (following an 8-week ibrutinib lead-in) to explore biomarkers (Arm 2, n = 20). The primary endpoint was the best overall response rate (ORR). The median age was 58 years; most had an Eastern Cooperative Oncology Group Performance Status of 0 (74%) and Stage III/IV disease (84%). At a median study follow-up of 34 months in Arm 1 and 29 months in Arm 2, ORRs were 85% [95% confidence interval (CI) 73-93] and 75% (95% CI 51-91), respectively, with complete responses in 40% and 50%. The median duration of response was not reached in either arm; 30-month progression-free and overall survival rates were 67% and 97% (Arm 1) and 65% and 100% (Arm 2). The most common adverse events were fatigue, diarrhoea and nausea. Higher grade (Grade 3/4) haematological, haemorrhagic and cardiac events occurred infrequently. Ibrutinib plus rituximab was active and tolerable in first-line follicular lymphoma.
Phase 2 study of a combined immunochemotherapy using rituximab and fludarabine in patients with chronic lymphocytic leukemia. [2022]This multicenter phase 2 trial investigated safety and efficacy of a new immunochemotherapeutic regimen combining rituximab (R) and fludarabine (F) in patients with fludarabine- and anthracycline-naive chronic lymphocytic leukemia (CLL). The rationale for using R + F includes single-agent efficacy of both drugs, in vitro synergism of R and F, and no apparent overlapping toxicity. Of 31 eligible patients with B-CLL enrolled, 20 were previously untreated and 11 relapsed. Treatment consisted of fludarabine administered at standard doses (25 mg/m(2)/d; days 1-5, 29-33, 57-61, and 85-89) and rituximab (375 mg/m(2)/d) given on days 57, 85, 113, and 151. Side effects such as fever, chills, and exanthema were generally mild (National Cancer Institute Common Toxicity Criteria [NCI-CTC] grade 1/2 in 48% and grade 3 and/or 4 in 3% of patients). Fever and chills were mainly associated with the first rituximab infusion. Hematologic toxicity included neutropenia (grade 1 and/or 2 in 26%, grade 3 and/or 4 in 42%) and thrombocytopenia (grade 1 and/or 2 in 19%, grade 3 and/or 4 in 9%). One patient died of cerebral bleeding during prolonged thrombocytopenia after the second cycle of fludarabine. There were a total of 32 infections in 16 patients, none of which was fatal. The overall response rate (complete remission [CR] and partial remission [PR]) was 87% (27 of 31 evaluable patients). In 20 previously untreated patients, 17 (85%) responded. Ten of 31 patients achieved CR (5 of 20 untreated; 5 of 11 pretreated; 9 of 21 Binet stage B, 1 of 10 Binet stage C). The median duration of response was 75 weeks. We conclude that the combination of rituximab and fludarabine is feasible and effective in patients with B-CLL.
Update on front-line therapy for follicular lymphoma: chemo-immunotherapy with rituximab and survival. [2015]Over the last three decades, there has been a wide range of options in the management of follicular lymphoma, including observation (watching and waiting), single-agent or combination (e.g., alkylating agents, anthracyclines or purine nucleoside analogs) radiation therapy, immunotherapy alone or in combination with chemotherapy, and interferon. A number of trials studying the treatment of follicular lymphoma patients have investigated the benefit of adding rituximab either concurrently or sequentially to chemotherapy. In the current review, these studies were selected based on the fact that they were randomized Phase III studies with two arms comparing chemotherapy alone with rituximab-based chemo-immunotherapy regimens. In September 2006, the US FDA approved the use of rituximab (Rituxan) as front-line treatment of patients with follicular lymphoma in combination with cyclophosphamide, vincristine and prednisone (R-CVP) as well as for the treatment of patients with low-grade non-Hodgkin's Lymphoma who achieve stable disease or better following first-line treatment with the same chemotherapy regimen (CVP --> R). The European Medicines Agency also approved the use of rituximab (MabThera) as front-line treatment of patients with stage III-IV disease in combination with CVP chemotherapy. In conclusion, although the clinical studies discussed in this article provide evidence for a progression-free survival benefit, overall survival advantage was clearly shown for the first time in a recent update of the initial study in patients with follicular lymphoma.
A phase 2 trial of extended induction epratuzumab and rituximab for previously untreated follicular lymphoma: CALGB 50701. [2021]Rituximab combined with chemotherapy has improved the survival of previously untreated patients with follicular lymphoma (FL). Nevertheless, many patients neither want nor can tolerate chemotherapy, leading to interest in biological approaches. Epratuzumab is a humanized anti-CD22 monoclonal antibody with efficacy in relapsed FL. Because both rituximab and epratuzumab have single-agent activity in FL, the antibody combination was evaluated as initial treatment of patients with FL.
Treatment of follicular lymphoma--a review. [2016]Follicular non-Hodgkin's lymphomas are indolent malignancies that have to be treated repeatedly when symptoms occur. Traditionally, several chemotherapeutic schedules are used. As a result there is a progressive shortening of the disease-free periods and no chemotherapeutical treatment has resulted in a survival benefit so far. The introduction of rituximab, a monoclonal anti-CD 20 antibody, and the association of rituximab with first-line chemotherapy has resulted in a prolongation of the progression-free survival (PFS) and seems to have an impact on (overall survival) OS. The low toxicity profile has even made maintenance therapy with rituximab possible. Trials with rituximab in maintenance suggest a survival benefit. The most optimal schedule of administration and the pharmaco-economical implications are, however, not obvious yet. Autologous stem cell transplantation (SCT) at first remission is another treatment option that has to be re-evaluated. Apart from that there is also the possibility of radio-immunotherapy, of which the advantage will have to become clear during follow-up of recent phase III trails.