Radiation Therapy + Rituximab for Follicular Lymphoma

Overseen By Bouthaina S. Dabaja

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Complementary medicines

Disqualifiers: Hepatitis, HIV, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: 20

130 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how radiation therapy combined with rituximab, an immune-boosting drug, can treat early-stage follicular lymphoma, a type of blood cancer. The study aims to determine if this combination can kill more cancer cells than radiation alone. One group of participants will receive both treatments, while the other group will receive only radiation followed by observation. The trial seeks individuals newly diagnosed with stage I or II follicular lymphoma, confirmed to be grade 1 or 2, who have not previously received radiation treatment at the lymphoma site. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have pre-existing cardiovascular disease requiring ongoing treatment, you may not be eligible to participate.

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

Research shows that combining radiation therapy with rituximab is generally well-tolerated for treating follicular lymphoma. Studies have found that radiation therapy can lead to excellent long-term results, with many patients achieving good survival rates. Rituximab, a treatment that helps the immune system fight cancer, has been used in many patients.

Reports indicate side effects, but they are often manageable. Patients receiving rituximab might experience reactions like fever or chills during treatment. Radiation therapy can sometimes cause skin irritation or tiredness. However, these treatments are commonly used for other conditions, indicating a known safety record.

Overall, while side effects can occur, the treatment is usually well-tolerated, and previous studies have shown promising results in controlling follicular lymphoma. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of radiation therapy and rituximab for treating follicular lymphoma because it offers a novel approach compared to the current standard treatments like chemotherapy and monoclonal antibodies alone. Rituximab is a monoclonal antibody that specifically targets the CD20 protein on the surface of B-cells, which are often involved in follicular lymphoma. By combining this targeted action with radiation therapy, which directly kills cancer cells in a localized area, this treatment has the potential to enhance effectiveness and reduce the likelihood of the disease progressing. Additionally, the use of rituximab after the initial radiation treatment could help sustain remission, offering a longer-term benefit.

What evidence suggests that this trial's treatments could be effective for follicular lymphoma?

Studies have shown that radiation therapy effectively treats various cancers by using high-energy x-rays to kill cancer cells. This well-established method can precisely target tumors. In this trial, one group of participants will receive both radiation therapy and rituximab, a monoclonal antibody effective against follicular lymphoma. Research indicates that rituximab has led to high survival rates, with up to 83% of patients experiencing good outcomes over ten years. Rituximab helps the immune system find and attack cancer cells. Another group in this trial will receive radiation therapy followed by observation. Combining these treatments might enhance their effectiveness, potentially killing more cancer cells than using either treatment alone. ^{6 7 8 9 10}

Who Is on the Research Team?

Bouthaina S. Dabaja

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for newly diagnosed patients with early-stage (I-II) grade 1 or 2 follicular lymphoma. Participants must have certain blood cell counts, good performance status, and proper liver and kidney function. Men must use contraception; women must be postmenopausal, surgically sterilized, or using two barrier methods of contraception.

Inclusion Criteria

Absolute neutrophil count (ANC) >= 1000/mm^3; Platelets >= 80,000/mm^3; Hemoglobin >= 8 g/dL; Bilirubin =< 1.5 times the upper limit of normal (ULN); Alanine aminotransferase (ALT) =< 2 times the ULN or aspartate aminotransferase (AST) =< 2 times the ULN; Performance status >= 2; Patients are required to have adequate renal function as indicated by a serum creatinine =< 2.5 mg/dL; No prior known allergic reaction to monoclonal antibodies; Male patients must agree to use a barrier method of contraception or agree to abstain from heterosexual activity for the duration of the study; Female patients must be willing to use two adequate barrier methods of contraception to prevent pregnancy or agree to abstain from heterosexual activity throughout the study or be post menopausal (free from menses > two years or surgically sterilized); Female patients of childbearing potential must have a negative serum pregnancy test (beta human chorionic gonadotropin [B HCG]) within 72 hours of receiving the first dose of rituximab; Patients must have the ability able to give informed consent

I have been newly diagnosed with early-stage follicular lymphoma, confirmed to be grade 1 or 2.

My doctor decides if I need lamivudine to prevent hepatitis B.

Exclusion Criteria

I have serious heart problems that need ongoing treatment.

I do not have any active infections needing treatment.

I've had radiation to the same area where my current cancer is, and can't have more without risking harm.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation and Rituximab Treatment

Patients undergo radiation therapy five days a week for 2.5 weeks and receive rituximab IV weekly for 4 weeks, followed by rituximab every 2 months for up to 4 additional doses

4-6 months

12 radiation visits, 4-8 rituximab visits

Observation

Patients undergo observation after radiation therapy

2.5 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 years

Follow-up at 3 and 6 months, every 6 months for 2 years, yearly for 3 years, then every 2 years for 10 years

What Are the Treatments Tested in This Trial?

Interventions

• Radiation Therapy
• Rituximab

Trial Overview The study tests the combination of radiation therapy with rituximab against cancer cells in patients with follicular lymphoma. Radiation aims to kill cancer cells directly while rituximab is an antibody that may help the immune system fight cancer.

How Is the Trial Designed?

Group I: Arm II (radiation therapy and observation) Experimental Treatment 2 Interventions

Patients undergo radiation therapy five days a week for 2.5 weeks and then undergo observation.

Group II: Arm I (radiation therapy and rituximab) Experimental Treatment 2 Interventions

Patients undergo radiation therapy five days a week for 2.5 weeks (12 treatments) and receive rituximab IV over 4-6 hours weekly with the start of radiation for 4 weeks and then every 2 months for up to 4 additional doses in the absence of disease progression or unacceptable toxicity.

Radiation Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in United States as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Canada as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Japan as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in China as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Switzerland as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 108 patients with early-stage follicular lymphoma, those treated with rituximab (R) alone or in combination with involved-field radiotherapy (R+IFRT) showed significantly better long-term disease control compared to those receiving only involved-field radiotherapy (IFRT).

The complete response rates were high across all groups, with 97% in the R+IFRT group, and both rituximab treatment options resulted in longer progression-free survival and time to next treatment without adding significant toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy for stage I/II follicular lymphoma (FL): is it time for a re-appraisal? Mondello, P., Steiner, N., Wasle, I., et al.[2014]

Radioimmunotherapy (RIT) is a safe and effective treatment for patients with indolent B-cell non-Hodgkin lymphomas, showing similar clinical outcomes for the two approved agents, 90Y-ibritumomab tiuxetan and 131I-tositumomab.

Recent changes, such as the removal of the pretreatment biodistribution evaluation for 90Y-ibritumomab tiuxetan, have increased its accessibility, and ongoing research is exploring its efficacy for other aggressive lymphoma types, with no increased risk of myelodysplastic syndrome compared to chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radioimmunotherapy for B-cell non-hodgkin lymphomas. Tomblyn, M.[2022]

In a study of 41 early-stage follicular lymphoma patients treated with rituximab and involved-field radiotherapy, all patients achieved complete remission (CR), and the estimated 5-year progression-free survival (PFS) rate was 90%.

The combination of rituximab with involved-field radiotherapy appears to enhance treatment efficacy without increasing toxicity, suggesting it could be a promising first-line treatment option for early-stage follicular lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy plus rituximab as first-line regimen for localized follicular lymphoma. Cencini, E., Puccini, B., Rigacci, L., et al.[2019]

The study found that (186)Re-epratuzumab, a radioimmunotherapy treatment for non-Hodgkin's lymphoma, is well tolerated at a maximum dose of 2.0 GBq/m², with no major toxicities reported during or after treatment.

Out of 15 patients treated, 5 showed objective responses, including one complete remission lasting 4 months and four partial remissions, indicating promising therapeutic potential for this treatment in relapsed or refractory NHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final results of a phase I radioimmunotherapy trial using (186)Re-epratuzumab for the treatment of patients with non-Hodgkin's lymphoma. Postema, EJ., Raemaekers, JM., Oyen, WJ., et al.[2017]

Radioimmunotherapy (RIT) uses radionuclides attached to tumor-targeting antibodies to deliver targeted radiation therapy, with successful examples like (90)Y-ibritumomab tiuxetan and (131)I-tositumomab approved for treating non-Hodgkin lymphoma.

Research is ongoing to improve RIT by minimizing unnecessary radiation exposure while enhancing its effectiveness, with promising results seen in preclinical studies for solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radioimmunotherapy: a specific treatment protocol for cancer by cytotoxic radioisotopes conjugated to antibodies. Kawashima, H.[2019]

In a study of 93 patients with early-stage follicular lymphoma, the combination of rituximab (R) with radiotherapy (RT) showed a complete response rate of 100%, suggesting enhanced effectiveness compared to RT alone, which had a 92% response rate.

The median progression-free survival (PFS) was significantly better for patients treated with R alone (4.9 years) compared to those receiving RT (3.3 years), indicating that R may provide superior disease control, although further research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy with rituximab may be better than radiotherapy alone in first-line treatment of early-stage follicular lymphoma: is it time to change the standard strategy? Janikova, A., Bortlicek, Z., Campr, V., et al.[2019]

In a study of 94 patients with stage I-II follicular lymphoma, adding rituximab to radiation therapy improved 10-year progression-free survival (PFS) to 64.6% compared to 50.7% for radiation alone, suggesting enhanced treatment efficacy.

The study highlights the importance of molecular disease monitoring, as positive PCR results at diagnosis were linked to a higher risk of relapse, indicating that understanding the molecular profile of the disease can inform treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of Rituximab to Involved-Field Radiation Therapy Prolongs Progression-free Survival in Stage I-II Follicular Lymphoma: Results of a Multicenter Study. Ruella, M., Filippi, AR., Bruna, R., et al.[2016]

The combination of radioimmunotherapy (RIT) using 131I-labelled anti-CEA MAb F(ab')2 fragments and radiotherapy (RT) at 20 Gy was tested in 6 patients with liver metastases from colorectal cancer, showing that this approach is feasible for targeting tumors while potentially minimizing side effects.

While reversible bone marrow and liver toxicity were observed in most patients, the treatment resulted in stable disease for 3 patients and a minor response in 1 patient, indicating some therapeutic benefit from the combined treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined radioimmunotherapy and radiotherapy of liver metastases from colorectal cancer: a feasibility study. Buchegger, F., Allal, AS., Roth, A., et al.[2018]

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]

Radioimmunotherapy using 90Y ibritumomab tiuxetan is both safe and effective for patients, with minimal radiation safety requirements for caregivers and patients, allowing for outpatient administration.

The administration of 90Y ibritumomab tiuxetan involves standard safety precautions, including universal precautions and acrylic shielding, highlighting the important role of oncology nurses in ensuring safe treatment delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation safety with yttrium 90 ibritumomab tiuxetan (Zevalin) radioimmunotherapy. Hendrix, C.[2019]

Radioimmunotherapy (RIT) using (90)Y-ibritumomab tiuxetan or (131)I-tositumomab is effective for treating B-cell non-Hodgkin lymphoma, particularly in relapsed or refractory follicular lymphoma, with overall response rates of 60-80%.

RIT is generally safe, with reversible myelosuppression as the primary side effect, and it can enhance treatment outcomes when used as consolidation therapy after initial chemotherapy, improving response rates and prolonging disease control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment recommendations for radioimmunotherapy in follicular lymphoma: a consensus conference report. Witzig, TE., Fishkin, P., Gordon, LI., et al.[2019]

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