Radiation Therapy vs Observation for B-Cell Lymphoma

Recruiting at 84 trial locations

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: International Extranodal Lymphoma Study Group (IELSG)

Must be taking: Rituximab, Anthracyclines

Disqualifiers: Other malignancies, Cardiac disease, HIV, others

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

Compensation: Varies

Number of Visits: 3

540 Participants Needed

Trial Summary

What is the purpose of this trial?

Primary mediastinal large B cell lymphoma is treated with a combination of chemotherapy and the monoclonal antibody rituximab (chemoimmunotherapy). Following chemoimmunotherapy patients receive radiation therapy if they have residues which may be active tumour. However at the end of chemoimmunotherapy the majority of patients show tissue scarring that is not necessarily active tumor. In recent years, PET/CT has proved to be a good tool to accurately identify active tumor from scar tissue in patients treated for mediastinal lymphoma.The purpose of this trial is to test whether radiation therapy is really necessary in patients where PET/CT has shown that the tumor is no longer active. Therefore we will compare radiation treatment with careful observation. Patients that at the end of conventional treatment of chemoimmunotherapy have a negative PET/CT (i.e., without residues suspected to contain active tumor), will randomly assigned to two different treatment groups: one treatment group will receive the radiation treatment, and the other treatment group will receive careful observation. The trial is planned according to a non-inferiority design aimed at demonstrating that progression free survival after the experimental treatment (observation) is not worse than after the standard comparator (mediastinal irradiation.Participation in this study could spare patients with complete remission at the end of chemo immunotherapy (PET/CT negative) radiation therapy that may be unnecessary.

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 data supports the effectiveness of the drug Rituximab for B-cell lymphoma?

Rituximab has been shown to improve response rates and survival in patients with B-cell lymphoma, particularly when combined with chemotherapy, achieving response rates of 90%-95% in certain types of non-Hodgkin's lymphoma. ^{1 2 3 4 5}

Is rituximab safe for humans?

Rituximab has been used for over 10 years and is generally considered safe, but it can increase the risk of infections, especially in people with weakened immune systems. Common side effects include fevers and chills during the first infusion, and there is a risk of serious infections like hepatitis B reactivation and a rare brain infection called PML. ^{4 6 7 8 9}

How does Rituximab treatment differ from other treatments for B-cell lymphoma?

Rituximab is unique because it targets the CD20 protein on B-cells, which helps the immune system destroy these cancerous cells. Unlike traditional chemotherapy, Rituximab is a monoclonal antibody (a lab-made protein that can bind to substances in the body) and is often used in combination with other treatments to improve outcomes in B-cell lymphoma. ^{2 10 11 12 13}

Research Team

Maurizio Martelli, MD

Principal Investigator

Università La Sapienza (Rome - Italy)

Andrew J Davies, MD

Principal Investigator

University of Southampton (UK)

Mary Gospodarowicz, MD

Principal Investigator

Princess Margaret Hospital Toronto (Canada)

Sally F Barrington, MD

Principal Investigator

St. Thomas' - London (UK)

Alberto Biggi, MD

Principal Investigator

AO S. Croce e Carle, Cuneo (Italia)

Annibale Versari, MD

Principal Investigator

S.Maria Nuova Hospital, Reggio Emilia (Italia)

Stèphane Chauvie, MD

Principal Investigator

AO S. Crtoce e Carle - Cuneo (Italy)

Luca Ceriani, MD

Principal Investigator

IOSI - Bellinzona (Switzerland)

Gianni Ciccone, MD

Principal Investigator

CPO Torino (Italy)

Eligibility Criteria

Adults with newly diagnosed primary mediastinal large B-cell lymphoma, CD20 positive, without extranodal disease outside the chest. They must have completed chemoimmunotherapy without autologous stem cell support and show no active tumor on PET/CT. Excludes pregnant women, those with certain psychological or medical conditions, HIV-positive individuals, and recent history of other cancers.

Inclusion Criteria

I am considered healthy enough to undergo chemotherapy and radiotherapy aimed at curing my condition.

Able and willing to give informed consent, and to undergo staging including PET scanning

I am receiving Rituximab with anthracycline chemotherapy but not stem cell support.

Exclusion Criteria

Known HIV-positive serology

Pregnant or lactating women

Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoimmunotherapy

Participants receive a combination of chemotherapy and the monoclonal antibody rituximab

Varies

Radiation or Observation

Participants with negative PET/CT scans are randomized to receive either radiation therapy or careful observation

Radiation: 30 Gy; Observation: 24 months of follow-up

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

3-month intervals for 24 months, then every 6 months until 5 years

Treatment Details

Interventions

• 3D-Conformal Radiotherapy (3D-CRT)
• observation
• Rituximab

Trial Overview This trial is testing if radiation therapy after chemoimmunotherapy is necessary for patients whose PET/CT scans don't show active tumors. Participants are randomly assigned to either receive radiation treatment or undergo careful observation to compare progression-free survival rates.

Participant Groups

Group I: observation Experimental Treatment 1 Intervention

Follow up visits are scheduled from randomization. Patients will be seen at 3-months intervals for 24 months, then every 6 months until 5 years from randomization.

Group II: mediastinal irradiation Active Control 1 Intervention

Radiotherapy will be delivered in this phase III protocol, as alternative to observation, as consolidation treatment in patients achieving a CR status (PET/CT scan negative) at the end of R-chemotherapy, with a total dose of 30 Gy.

Who Is Running the Clinical Trial?

International Extranodal Lymphoma Study Group (IELSG)

Lead Sponsor

Trials

29

Recruited

3,700+

Findings from Research

Rituximab was the first monoclonal antibody approved for cancer therapy and has significantly improved survival rates in patients with diffuse large cell lymphoma when combined with CHOP chemotherapy.

Initially approved in 1997 for relapsed or refractory low-grade or follicular, CD20-positive, B-cell non-Hodgkin's lymphoma, rituximab is also being researched for other B-cell malignancies and nonmalignant diseases like autoimmune disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab: review and clinical applications focusing on non-Hodgkin's lymphoma. King, KM., Younes, A.[2015]

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]

Rituximab has significantly improved outcomes for patients with Non-Hodgkin's lymphoma (NHL), particularly in aggressive forms like diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL).

The treatment is generally well-tolerated by patients and has been shown to be cost-effective, making it a valuable option in both initial and relapsed cases of B cell NHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in the treatment of non-Hodgkin's lymphoma--a critical evaluation of randomized controlled trials. Griffin, MM., Morley, N.[2020]

Rituximab has significantly improved survival rates in patients with non-Hodgkin lymphomas, but there is a lack of comprehensive data on its long-term safety, indicating a need for extended patient follow-up.

Current literature provides limited guidance on systematic follow-up models for patients receiving rituximab, highlighting the necessity for developing monitoring strategies to ensure patient safety and optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical follow-up for patients on rituximab therapy for non-Hodgkin lymphoma: what is the evidence? Hegele, V., Stoll, P., Wüst, D., et al.[2021]

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]

In a study of 365 multiple sclerosis patients treated with rituximab over four years, the treatment showed a very low annualized relapse rate (ARR) of 0.03, indicating high efficacy in preventing disease relapses.

While rituximab was generally safe, with 79% of patients achieving no evidence of disease activity (NEDA-3), there were notable risks of infections and neutropenia, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of rituximab as first- and second line treatment in multiple sclerosis - A cohort study. Torgauten, HM., Myhr, KM., Wergeland, S., et al.[2022]

Rituximab has been shown to be very safe over more than 10 years of use, but it can significantly increase the risk of infections, especially in patients with low-grade lymphoma or severe immunodeficiency, such as those with HIV or on immunosuppressive therapies.

The most critical infection associated with rituximab is hepatitis B reactivation, which can lead to severe liver failure; therefore, screening for hepatitis B and considering preemptive antiviral treatment is essential for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab-associated infections. Gea-Banacloche, JC.[2020]

References

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

Rituximab therapy of B-cell neoplasms. [2022]

2. Italy pubmed.ncbi.nlm.nih.gov

Impact on survival through consolidation radiotherapy for diffuse large B-cell lymphoma: a comprehensive meta-analysis. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Rituximab: review and clinical applications focusing on non-Hodgkin's lymphoma. [2015]

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

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

5. England pubmed.ncbi.nlm.nih.gov

Rituximab in the treatment of non-Hodgkin's lymphoma--a critical evaluation of randomized controlled trials. [2020]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Pharmaceutical follow-up for patients on rituximab therapy for non-Hodgkin lymphoma: what is the evidence? [2021]

7. 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]

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

Safety and efficacy of rituximab as first- and second line treatment in multiple sclerosis - A cohort study. [2022]

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

Rituximab-associated infections. [2020]

10. Italy pubmed.ncbi.nlm.nih.gov

Radioimmunotherapy of B-cell lymphoma with radiolabelled anti-CD20 monoclonal antibodies. [2018]

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

Role of radiation therapy in primary breast diffuse large B-cell lymphoma in the Rituximab era: a SEER database analysis. [2019]

12. England pubmed.ncbi.nlm.nih.gov

Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial. [2022]

13. Ireland pubmed.ncbi.nlm.nih.gov

Changes in treatment patterns and impact of radiotherapy for early stage diffuse large B cell lymphoma after Rituximab: A population-based analysis. [2018]