Radiation Therapy vs Observation for B-Cell Lymphoma

Not currently recruiting at 93 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether radiation therapy is necessary for patients with primary mediastinal large B-cell lymphoma after treatment with chemoimmunotherapy, which combines chemotherapy and the antibody rituximab. The study compares two groups: one receiving radiation therapy and the other undergoing regular check-ups without radiation. The aim is to determine if skipping radiation is safe and effective, particularly when a PET/CT scan shows no active tumor. Suitable candidates for this trial have a confirmed diagnosis of this lymphoma type and no signs of disease spread outside the chest. The goal is to discover if careful observation can provide similar outcomes to radiation without additional treatment. As an unphased trial, this study allows patients to contribute to research that could simplify treatment and enhance quality of life.

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 prior data suggests that radiation therapy and observation are safe for patients with B-cell lymphoma?

Research has shown that radiation therapy can benefit patients with B-cell lymphoma after chemoimmunotherapy, especially when combined with rituximab. One study found that patients who received radiation therapy experienced good results and survival rates. However, another study found that some patients did well without radiation if their PET/CT scan showed no active cancer after initial treatment.

Radiation therapy is usually well-tolerated but can cause side effects. Common side effects include tiredness and skin reactions, while rare ones might involve harm to nearby organs. The safety of radiation is generally considered acceptable, especially when the benefits outweigh the risks.

The observation group in this trial involves regular check-ups without additional treatment. This option avoids radiation side effects but requires careful monitoring to detect any changes early.

In summary, both radiation therapy and observation have proven safe in different situations, depending on the specifics of the patient's condition. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores whether radiation therapy as a consolidation treatment can be a game-changer for patients with B-cell lymphoma. Unlike many current treatments that involve extended chemotherapy sessions, radiation therapy might offer a more targeted approach to eliminate residual disease after initial chemotherapy. Additionally, the study also examines the potential benefits of simply observing patients who achieve complete remission, potentially reducing unnecessary treatments and their side effects. This dual approach could lead to more personalized and less invasive strategies for managing B-cell lymphoma.

What evidence suggests that this trial's treatments could be effective for B-cell lymphoma?

Research has shown that many patients with primary mediastinal large B cell lymphoma achieve excellent survival rates after chemoimmunotherapy, even without additional radiation. One study found a survival rate of 96.3% at 2 years and 95.1% at 5 years without radiation. In this trial, one group of participants will undergo observation, which involves monitoring patients without additional radiation if their PET/CT scans show no active tumor after initial treatment. This approach aims to avoid unnecessary radiation, which carries its own risks, while maintaining high survival rates. Another group will receive mediastinal irradiation as a consolidation treatment to compare outcomes. ^{1 4 6 7 8}

Who Is on the 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)

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4986477/

from 3D conformal radiotherapy (3DCRT) to intensity ... 49 patients were treated by 3DCRT and 20 patients by IMRT. The median dose received by patients treated for NHL was 40 Gy (range: 36–44 Gy), and the median dose ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5484240/

Treatment outcome of diffuse large B-cell lymphoma ... Excellent local control and survival rates can be achieved with R-CHOP followed by radiotherapy in patients with DLBCL involving the head and neck.

3. advancesradonc.com advancesradonc.com/article/S2452-1094(22)00122-1/fulltext

What Is the Right Regimen for Palliation? One-hundred and sixty-nine patients were treated with 205 RT courses (73 [36%] salvage, 132 [64%] palliative), and hypofractionated RT was used ...

4. ar.iiarjournals.org ar.iiarjournals.org/content/41/10/5131

Intensity-modulated Radiotherapy in Patients With ... Results: The median follow-up was 42 months. Patients treated with IMRT experienced higher overall responde rate than patients who received 3DCRT (85% vs. 73%, ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO-24-01373

Omission of Radiotherapy in Primary Mediastinal B-Cell ... The overall survival rate was 96.3% (95% CI, 94.3 to 97.6) at 2 years and 95.1% (95% CI, 92.8 to 96.6) at 5 years. OS, overall survival; PFS, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12427289/

Clinical Outcomes and Safety of Ultra-Low-Dose ... This systematic review was conducted to address inconsistencies in the reported clinical outcomes and safety profile of ultra-low-dose ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2452109422001221

Radiation Therapy for Relapsed or Refractory Diffuse ... To report objective response rates (ORR), time to local failure (TTLF), and overall survival (OS) among patients with relapsed or refractory diffuse large ...

8. mdpi.com mdpi.com/2072-6694/16/3/649

Long-Term Results of IFRT vs. ISRT in Infradiaphragmal ... According to the National Cancer Institute data from 2013 and 2019, the 5-year overall survival rate for patients with diffuse large B-cell ...