AZD0486 + Rituximab for Follicular Lymphoma
Recruiting in Palo Alto (17 mi)
+37 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: AstraZeneca
Disqualifiers: CNS lymphoma, Active infection, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This is a global, randomised, Phase III, multicentre, open-label study evaluating the efficacy, safety and the degree of added benefit of the AZD0486 plus rituximab combination compared to Investigator's choice of 3 standard immunochemotherapy regimen, conducted in participants with untreated FL.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What evidence supports the effectiveness of the drug combination AZD0486 and Rituximab for treating follicular lymphoma?
Rituximab, when combined with chemotherapy, has been shown to improve response rates and progression-free survival in patients with follicular lymphoma, and it is considered a standard treatment. Although specific data on AZD0486 is not provided, the combination of rituximab with other biological agents has been effective in enhancing treatment outcomes.
12345What safety data exists for AZD0486 + Rituximab treatment?
Rituximab, used in various conditions, generally has tolerable side effects like fevers and chills during the first infusion, but can also cause rare cases of severe thrombocytopenia (low platelet count). It is considered safe for long-term use in some lymphomas, though some patients may experience reversible low blood cell counts.
678910What makes the drug AZD0486 + Rituximab unique for treating follicular lymphoma?
The combination of AZD0486, a novel bispecific antibody targeting CD19 and CD3, with Rituximab, a well-established monoclonal antibody targeting CD20, offers a unique approach by engaging both T-cells and B-cells to enhance the immune response against follicular lymphoma, potentially improving treatment outcomes compared to standard therapies that typically target only one type of cell.
67111213Eligibility Criteria
This trial is for patients with untreated Follicular Lymphoma. Participants must meet certain health criteria to join, but specific inclusion and exclusion details are not provided here.Inclusion Criteria
My liver, blood, kidney, and heart are functioning well.
My lymphoma is classified as FL Grade 1-3A.
I need treatment for my condition as per GELF guidelines.
+4 more
Exclusion Criteria
I cannot receive BR, RCVP, or R-CHOP treatments due to health reasons.
Presence of >5000 circulating lymphoma cells
My lymphoma is either Grade 3B or suspected to be transforming into a more aggressive form.
+2 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Safety Run-in
This part will compare dose levels of AZD0486 in combination with rituximab to establish the RP3D
Up to 1 year
Phase III Treatment
Participants receive AZD0486 plus rituximab or Investigator's choice of standard chemoimmunotherapy regimen
Up to 10 years
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 10 years
Participant Groups
The study tests the effectiveness and safety of a new combination: AZD0486 plus rituximab against standard immunochemotherapy regimens (R-CHOP, R-CVP, BR) in untreated Follicular Lymphoma patients.
3Treatment groups
Experimental Treatment
Active Control
Group I: Rituximab, AZD0486 - BExperimental Treatment1 Intervention
AZD0486 regimen B plus rituximab
Group II: Rituximab, AZD0486 - AExperimental Treatment1 Intervention
AZD0486 regimen A plus rituximab
Group III: ChemoimmunotherapyActive Control3 Interventions
Investigator's choice between 3 standard immunochemotherapy regimen (R-CHOP or R-CVP followed by rituximab maintenance, or B-R)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Research SiteOshawa, Canada
Research SiteChicoutimi, Canada
Research SiteHamilton, Canada
Research SiteMontreal, Canada
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Who Is Running the Clinical Trial?
AstraZenecaLead Sponsor
References
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.
The Use of 20% Subcutaneous Immunoglobulin Replacement Therapy in Patients With B Cell Non-Hodgkin Lymphoma With Humoral Immune Dysfunction After Treatment With Rituximab. [2021]Rituximab is an anti-CD20 chimeric antibody used to treat autoimmune conditions and B cell neoplasms. We characterized immunoglobulin (Ig) levels and vaccine responses in rituximab-treated B cell non-Hodgkin lymphoma (NHL) patients. Patients with impaired vaccine responses were offered therapy with 20% subcutaneous (subq) Ig.
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.
Spotlight on rituximab in chronic lymphocytic leukemia, low-grade or follicular lymphoma, and diffuse large B-cell lymphoma. [2017]Rituximab (MabThera®, Rituxan®) is a chimeric mouse anti-human CD20 monoclonal antibody. This article reviews the use of intravenous rituximab in the treatment of chronic lymphocytic leukemia (CLL), low-grade or follicular lymphoma, and diffuse large B-cell lymphoma. The addition of rituximab to fludarabine plus cyclophosphamide significantly prolonged progression-free survival both in previously untreated patients with CLL and in those with relapsed or refractory CLL, according to the results of two randomized, open-label, multicenter trials. In patients with previously untreated advanced follicular lymphoma, the addition of rituximab to chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP]; cyclophosphamide, vincristine, and prednisone [CVP]; mitoxantrone, chlorambucil, and prednisolone; or cyclophosphamide, doxorubicin, etoposide, and prednisolone) was generally associated with better outcomes than chemotherapy alone in randomized, multicenter trials. In a similarly designed trial, progression-free survival was significantly longer in previously untreated patients with follicular lymphoma, other indolent lymphomas, or mantle-cell lymphoma who received rituximab plus bendamustine than in those receiving rituximab plus CHOP. Monotherapy with rituximab also demonstrated efficacy in patients with relapsed or refractory low-grade or follicular lymphoma, according to the results of noncomparative trials. In terms of maintenance therapy, progression-free survival was significantly prolonged with rituximab maintenance therapy versus observation alone in patients with advanced indolent lymphoma who had not progressed following first-line therapy with CVP and in patients with relapsed or refractory follicular lymphoma who had responded to CHOP (with or without rituximab), according to the results of randomized, open-label, multicenter trials. In four randomized, open-label, multicenter trials in younger or elderly patients with previously untreated diffuse large B-cell lymphoma, event-free survival, failure-free survival, progression-free survival, and overall survival were generally improved to a significant extent by the addition of rituximab to CHOP or CHOP-like chemotherapy. Intravenous rituximab was generally well tolerated in patients with CLL, low-grade or follicular lymphoma, or diffuse large B-cell lymphoma, both as monotherapy and when administered in combination with chemotherapy. Infusion reactions were one of the most commonly occurring adverse events in patients receiving intravenous rituximab. The results of pharmacoeconomic modeling analyses demonstrated that rituximab appears to be cost effective in patients with previously untreated follicular lymphoma, in patients with follicular lymphoma receiving rituximab maintenance therapy following treatment for relapsed or refractory disease, and in patients with previously untreated diffuse large B-cell lymphoma. In conclusion, rituximab remains a valuable therapy in patients with CLL, low-grade or follicular lymphoma, and diffuse large B-cell lymphoma and, in a variety of treatment settings, represents the standard of care.
Subcutaneous rituximab with recombinant human hyaluronidase in the treatment of non-Hodgkin lymphoma and chronic lymphocytic leukemia. [2018]The anti-CD20 monoclonal antibody rituximab (MabThera®/Rituxan®) has been proven to improve outcomes in a range of B-cell malignancies. Initially developed as a formulation for intravenous infusion, administration times for rituximab can be prolonged and associated with infusion-related reactions, prompting a combined clinical development program investigating subcutaneous delivery in combination with recombinant human hyaluronidase. As this program comes to fruition, this article reviews the evidence demonstrating subcutaneous rituximab to have noninferior pharmacokinetics when delivered at a fixed-dose as well as equivalent clinical outcomes in the treatment of follicular lymphoma, chronic lymphocytic leukemia and diffuse large B-cell lymphoma. This mode of delivery is more preferable to patients and healthcare professionals and is associated with time and cost savings.
Use of rituximab, the new FDA-approved antibody. [2019]Rituximab (Rituxan; IDEC Pharmaceuticals, San Diego, CA) is the first monoclonal antibody approved by the US Food and Drug Administration for the treatment of cancer. It is a genetically engineered chimeric (murine-human) monoclonal antibody (mAb) directed against the CD20 antigen found on the surface of normal and malignant B cells. Multicenter studies have demonstrated its efficacy against relapsed low-grade and follicular non-Hodgkin's lymphoma (NHL). The mAb demonstrated tolerable side effects, primarily limited to fevers and chills associated with the first infusion. The currently recommended dosage is 375 mg/m2/infusion, given weekly for 4 weeks. Because of its human component, rituximab has low immunogenicity and should not significantly hinder future retreatment. Future studies will evaluate the antitumor activity of rituximab combined with various other chemotherapeutic or biologic agents in the treatment of B-cell lymphoma and other CD20-positive lymphoid neoplasms.
Rescue Therapy Using Rituximab for Multiple Sclerosis. [2017]The aim of the study was to describe the effectiveness and safety data of rituximab in a group of patients with relapsing-remitting multiple sclerosis (MS) treated with rituximab due to failure of previous treatments or concomitant autoimmune diseases.
Long-term molecular remissions in patients with indolent lymphoma treated with rituximab as a single agent or in combination with interferon alpha-2a: a randomized phase II study from the Nordic Lymphoma Group. [2021]The purpose of this phase II randomized trial was to evaluate the effect and safety of interferon-alpha2a (IFN) in combination with extended dosing rituximab in patients with symptomatic, advanced indolent lymphoma responding to a standard single course of rituximab. Totally 123 patients were treated with rituximab 375 mg/m2 once weekly for 4 weeks leading to 14 complete response (CR; 11%), 56 partial response (PR; 46%), and 13 minor responses (MR; 11%). Patients achieving either PR or MR were randomized to four more infusions of rituximab alone (n = 36) or in combination with five weeks of IFN (n = 33), with an overall response rate (CR + PR) of 78% and 94%, respectively. Significantly more patients in the combination arm improved their response from PR/MR to CR (P or = 24 months (72% versus 50%), respectively. Overall, 26 out of the 52 patients who achieved CR underwent minimal residual disease (MRD) evaluation. Totally 17 of these (65%) achieved MRD negativity, 14 of whom remain in CR after 4.8 years' follow-up. The addition of IFN to rituximab was generally safe, but reversible thrombocytopenia and neutropenia were noted in one and six patients, respectively, requiring a reduction in the IFN dose. Extended rituximab is effective and well tolerated and combination with IFN seems to improve both the quality and duration of the responses, providing the opportunity to achieve long-term molecular CRs and prolonged failure-free survival without chemotherapy.
Rituximab-induced severe acute thrombocytopenia in a patient with splenic marginal zone lymphoma. [2023]Rituximab, which is widely used in the treatment of B-cell lymphoma, is a chimeric monoclonal antibody directed against the CD20 antigen. Rituximab has many side effects, mainly allergic and neurological. Rituximab may cause thrombocytopenia in the long term after administration. Rare cases of rituximab-induced acute thrombocytopenia have been reported in the literature.
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.
Use of rituximab in combination with conventional chemotherapy for the treatment of non-Hodgkin's lymphoma of the head and neck. [2015]Rituximab, an anti-CD20 chimeric monoclonal antibody that specifically depletes mature B cells, is an effective single agent in the treatment of relapsed or refractory indolent lymphomas, and has been shown to improve the survival rate of elderly patients with diffuse large-B-cell lymphoma when used in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP).
INFECTIOUS COMPLICATIONS AS A PREDICTOR OF MORTALITY IN PATIENTS WITH NON-HODGKIN LYMPHOMA RECEIVING RITUXIMAB-CONTAINING CHEMOTHERAPY. [2022]Rituximab is a monoclonal antibody that increases the disease-free and overall survival of patients with non-Hodgkin lymphoma (NHL) CD20+. The objective of this study is to describe the prevalence and spectrum of infections in patients with NHL receiving rituximab-containing chemotherapy and the impact on survival.