AZD0486 + Rituximab for Follicular Lymphoma

Recruiting at 53 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

Trial Summary

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. ^{1 2 3 4 5}

What 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. ^{6 7 8 9 10}

What 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. ^{6 7 11 12 13}

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.

Research Team

Chan Cheah

Principal Investigator

Sir Charles Gairdner Hospital (SCGH)

Eligibility 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.

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.

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

Treatment Details

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.

Participant Groups

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)

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

Findings from Research

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]

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-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]

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]

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. United States 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. [2016]

3. United States 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. [2021]

4. England pubmed.ncbi.nlm.nih.gov

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

5. New Zealand pubmed.ncbi.nlm.nih.gov

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

6. England pubmed.ncbi.nlm.nih.gov

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

7. United States pubmed.ncbi.nlm.nih.gov

Use of rituximab, the new FDA-approved antibody. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Rescue Therapy Using Rituximab for Multiple Sclerosis. [2017]

9. United States 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. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Rituximab-induced severe acute thrombocytopenia in a patient with splenic marginal zone lymphoma. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Evolving role of rituximab in the treatment of patients with non-Hodgkin's lymphoma. [2015]

12. Greece 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. [2015]

13. Mexico pubmed.ncbi.nlm.nih.gov

INFECTIOUS COMPLICATIONS AS A PREDICTOR OF MORTALITY IN PATIENTS WITH NON-HODGKIN LYMPHOMA RECEIVING RITUXIMAB-CONTAINING CHEMOTHERAPY. [2022]