AZD0486 + Rituximab for Follicular Lymphoma

Recruiting at 116 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Disqualifiers: CNS lymphoma, Active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

1015 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for people with follicular lymphoma, a type of blood cancer. Researchers aim to determine if adding AZD0486, an experimental drug, to rituximab, a common lymphoma treatment, is more effective than standard options. Participants will be randomly assigned to receive either the new combination or a standard treatment. The trial seeks individuals who have not yet received treatment for follicular lymphoma and require systemic (whole-body) therapy. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research is testing the safety of combining AZD0486 with rituximab for people with follicular lymphoma. AZD0486 is not yet approved for any condition, so its safety in humans remains under study. Rituximab, however, is FDA-approved for other conditions and is generally well-tolerated. Known side effects of rituximab include fever, chills, and reactions during infusion.

Since this study is in Phase 3, earlier trials have shown some safety and effectiveness of AZD0486 in smaller groups. Phase 3 trials involve more participants and help determine how well the treatment is tolerated. This indicates that AZD0486 had an acceptable safety profile in earlier trials. However, participants should be aware that unknown side effects may still emerge as the treatment undergoes further testing. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AZD0486 in combination with rituximab for treating follicular lymphoma because it introduces a novel approach compared to the current standard immunochemotherapy options like R-CHOP, R-CVP, or B-R. Unlike these traditional treatments, AZD0486 might offer a new mechanism that enhances the effectiveness of rituximab, potentially leading to better outcomes. Additionally, having multiple regimens (A and B) allows for flexibility in tailoring treatment to individual patient needs, which could improve both efficacy and tolerability. This innovative combination aims to provide a more targeted and potentially more effective therapy for patients with follicular lymphoma.

What evidence suggests that the AZD0486 and rituximab combination could be an effective treatment for follicular lymphoma?

This trial will evaluate the effectiveness of combining AZD0486 with rituximab for treating follicular lymphoma. Participants will receive either AZD0486 regimen A plus rituximab, AZD0486 regimen B plus rituximab, or a standard chemoimmunotherapy regimen as an active comparator. Research has shown that AZD0486, an antibody targeting specific proteins on cancer cells, may enhance the immune system's ability to fight cancer. Early studies suggested that the combination of AZD0486 with rituximab is effective for patients whose cancer has returned or hasn't responded to other treatments, and it might also benefit those who haven't been treated yet. Rituximab is already a successful treatment for many lymphoma cases. Together, these drugs aim to improve treatment by more directly targeting cancer cells. ^{1 2 3 4 6}

Who Is on the Research Team?

Chan Cheah

Principal Investigator

Sir Charles Gairdner Hospital (SCGH)

Are You a Good Fit for This Trial?

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.

Exclusion Criteria

Presence of >5000 circulating lymphoma cells

I cannot receive BR, RCVP, or R-CHOP treatments due to health reasons.

My lymphoma is either Grade 3B or suspected to be transforming into a more aggressive form.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• AZD0486
• Rituximab

Trial Overview 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.

How Is the Trial Designed?

Group I: Rituximab, AZD0486 - B Experimental Treatment 1 Intervention

AZD0486 regimen B plus rituximab

Group II: Rituximab, AZD0486 - A Experimental Treatment 1 Intervention

AZD0486 regimen A plus rituximab

Group III: Chemoimmunotherapy Active Control 3 Interventions

Investigator's choice between 3 standard immunochemotherapy regimen (R-CHOP or R-CVP followed by rituximab maintenance, or B-R followed by rituximab maintenance)

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

In a study of 60 patients with symptomatic or bulky follicular lymphoma, a combination of short-course chemoimmunotherapy (CHOP-R) followed by radioimmunotherapy (RIT) led to a significant increase in complete response (CR) rates, from 40% after CHOP-R to 82% after RIT, as assessed by imaging.

The study found that patients who did not achieve a complete metabolic response on PET imaging after CHOP-R had a higher risk of relapse, highlighting the importance of early PET assessment in predicting treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of short-course CHOP-R followed by 90Y-ibritumomab tiuxetan and extended rituximab in previously untreated follicular lymphoma. Jacobs, SA., Swerdlow, SH., Kant, J., et al.[2016]

Rituximab significantly improves progression-free survival in patients with chronic lymphocytic leukemia (CLL) and follicular lymphoma when combined with chemotherapy, based on results from multiple randomized trials involving various treatment regimens.

The drug is generally well tolerated, with infusion reactions being the most common side effect, and it is considered cost-effective for treating certain types of lymphoma, reinforcing its status as a standard care option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on rituximab in chronic lymphocytic leukemia, low-grade or follicular lymphoma, and diffuse large B-cell lymphoma. Keating, GM.[2017]

In a study of 18 elderly patients with non-Hodgkin's lymphoma, the combination of rituximab and CHOP showed a high response rate of 91%, indicating its potential effectiveness as a treatment option.

While the overall survival and disease-free survival rates were slightly better in the rituximab plus CHOP group (91%) compared to CHOP alone (83% overall survival), the differences were not statistically significant, suggesting that further research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of rituximab in combination with conventional chemotherapy for the treatment of non-Hodgkin's lymphoma of the head and neck. Manolopoulos, L., Gomatos, IP., Leandros, E., et al.[2015]

In a study of 265 patients with non-Hodgkin lymphoma receiving rituximab, 177 infections were reported, with febrile neutropenia and mucosal barrier injury-related infections being the most common, highlighting the need for careful monitoring during treatment.

The study found that age over 60, failure to achieve a complete response, and the occurrence of infections significantly increased the risk of death, emphasizing the importance of screening for infections like tuberculosis before starting rituximab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

INFECTIOUS COMPLICATIONS AS A PREDICTOR OF MORTALITY IN PATIENTS WITH NON-HODGKIN LYMPHOMA RECEIVING RITUXIMAB-CONTAINING CHEMOTHERAPY. Meza-Meneses, P., Cornejo-Juárez, P., Vilar-Compte, D., et al.[2022]

Rituximab is the first monoclonal antibody approved for treating B-cell lymphomas, showing significant effectiveness in conditions like follicular lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma.

The combination of rituximab with standard chemotherapy agents (cyclophosphamide, doxorubicin, vincristine, and prednisone) has achieved the highest efficacy reported for treating diffuse large B-cell lymphoma and follicular lymphoma, while maintaining low toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolving role of rituximab in the treatment of patients with non-Hodgkin's lymphoma. Traullé, C., Coiffier, BB.[2015]

Subcutaneous administration of rituximab, combined with recombinant human hyaluronidase, shows noninferior pharmacokinetics compared to the traditional intravenous infusion, making it a viable alternative for patients.

This new delivery method not only maintains equivalent clinical outcomes for treating B-cell malignancies like follicular lymphoma and chronic lymphocytic leukemia but also offers advantages in terms of patient preference, time efficiency, and cost savings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous rituximab with recombinant human hyaluronidase in the treatment of non-Hodgkin lymphoma and chronic lymphocytic leukemia. Hill, SL., Davies, A.[2018]

Rituximab is the first FDA-approved monoclonal antibody for cancer treatment, specifically targeting the CD20 antigen on B cells, and has shown efficacy in treating relapsed low-grade and follicular non-Hodgkin's lymphoma in multicenter studies.

The treatment is generally well-tolerated, with side effects mainly consisting of mild fevers and chills during the first infusion, and its low immunogenicity allows for potential future treatments without significant complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of rituximab, the new FDA-approved antibody. Leget, GA., Czuczman, MS.[2019]

In a study of 12 patients with relapsing-remitting multiple sclerosis (MS), rituximab was found to be safe and well-tolerated, with no serious adverse reactions reported during an average follow-up of 40 months.

Rituximab treatment resulted in no clinical relapses and improved disability scores in 11 out of 12 patients, indicating its effectiveness for those who had previously failed other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rescue Therapy Using Rituximab for Multiple Sclerosis. Berenguer-Ruiz, L., Sempere, AP., Gimenez-Martinez, J., et al.[2017]

In a phase II trial involving 123 patients with advanced indolent lymphoma, the combination of interferon-alpha2a (IFN) with extended dosing of rituximab significantly improved response rates, with 94% of patients achieving an overall response compared to 78% with rituximab alone.

The addition of IFN not only increased the number of patients achieving complete responses (CR) but also helped maintain these responses for over 24 months in 72% of patients, indicating that this combination therapy can lead to long-term benefits without the need for chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Kimby, E., Jurlander, J., Geisler, C., et al.[2021]

Rituximab, a treatment for B-cell lymphoma, can cause severe acute thrombocytopenia, as demonstrated in a case where a 51-year-old patient experienced a drastic drop in platelet count from 112,000/μL to 5,000/μL shortly after administration.

Despite the risk of thrombocytopenia, the patient's platelet count recovered to 122,000/μL within two weeks, indicating that with careful monitoring and management, patients can continue receiving rituximab safely.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab-induced severe acute thrombocytopenia in a patient with splenic marginal zone lymphoma. Kars, TU., Yorgancı, ZF., Yaşkıran, O., et al.[2023]

Rituximab is highly effective for treating low-grade CD20+ lymphoma, especially when combined with chemotherapy, which is the standard treatment for follicular lymphoma (FL).

The efficacy of rituximab can be enhanced by combining it with biological agents like interferon-alpha-2a, bortezomib, or lenalidomide, but more research is needed to determine the best combinations and timing of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological therapy doublets: pairing rituximab with interferon, lenalidomide, and other biological agents in patients with follicular lymphoma. Kimby, E.[2021]

Rituximab-treated patients with B cell non-Hodgkin lymphoma (NHL) showed significant humoral immunodeficiency, with only 20% responding to diphtheria and pneumococcal vaccinations, despite having relatively normal IgG levels.

Subcutaneous immunoglobulin (subq Ig) therapy was well-tolerated and significantly increased serum IgG levels, leading to a reduction in nonneutropenic infections, indicating its efficacy as a supportive treatment for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Use of 20% Subcutaneous Immunoglobulin Replacement Therapy in Patients With B Cell Non-Hodgkin Lymphoma With Humoral Immune Dysfunction After Treatment With Rituximab. Mustafa, SS., Jamshed, S., Vadamalai, K., et al.[2021]

Rituximab combined with chemotherapy significantly improves response rates and progression-free survival (PFS) in patients with advanced stage symptomatic follicular non-Hodgkin's lymphoma (NHL), without increasing toxicity, based on data from large-scale phase III trials.

Patients with follicular NHL should receive rituximab plus chemotherapy as first-line treatment, and maintenance therapy with rituximab has been shown to further prolong PFS in both relapsed and newly diagnosed patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of rituximab in patients with follicular lymphoma. Marcus, R.[2019]

Citations

1. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D7401C00001

A study of AZD0486 plus Rituximab in previously untreated ... 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 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06549595

NCT06549595 | A Study of AZD0486 Plus Rituximab in ... 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 ...

3. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/526315

A Study of AZD0486 Plus Rituximab in Previously Untreated ... 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 ...

4. ashpublications.org ashpublications.org/bloodneoplasia/article/2/4/100131/537831/Current-landscape-of-frontline-and-relapsed

Current landscape of frontline and relapsed follicular ... AZD0486 is a novel immunoglobulin G4 (IgG4) fully human CD3×CD19 bispecific antibody that was recently reported to be effective in R/R FL (NCT04594642).57 The ...

5. app.1104health.com app.1104health.com/start/physician/NCT06549595/

Phase 3, global randomized study in untreated follicular ... This Phase 3 trial evaluates the efficacy and safety of AZD0486 plus rituximab compared to standard chemoimmunotherapy in patients with previously untreated ...

6. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/526315

A Study of AZD0486 Plus Rituximab in Previously ... 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 ...