Rituximab + Chemotherapy +/- Lenalidomide for Lymphoma

Not currently recruiting at 589 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Anticoagulants, Aspirin

Must not be taking: Erythroid stimulants

Disqualifiers: CNS lymphoma, Active malignancy, others

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

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

Compensation: Varies

Number of Visits: 3

Duration: 18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates the effectiveness of combining rituximab and chemotherapy, with or without lenalidomide, for treating diffuse large B cell lymphoma. Rituximab, a monoclonal antibody, may stop cancer cells from growing, while chemotherapy uses various drugs to kill cancer cells or prevent their spread. Lenalidomide might enhance the immune system's ability to fight cancer. The study seeks participants who have been newly diagnosed with stage II-IV disease and have not yet received treatment. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must not be receiving any other treatment for lymphoma, and certain medications like erythroid stimulating agents are not allowed. It's best to discuss your current medications with the trial team to ensure they don't interfere with the study.

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

Research has shown that a combination of rituximab, chemotherapy, and lenalidomide has been tested for safety in people with lymphoma. One study focused on older patients with diffuse large B cell lymphoma and found this treatment safe and effective. Although the study involved older adults, the results suggest that others may also tolerate the treatment well.

Rituximab and the chemotherapy drugs—cyclophosphamide, doxorubicin, vincristine, and prednisone—form a treatment plan known as R-CHOP, commonly used for lymphoma. This combination is well-known for its safety and is widely used for similar conditions.

Adding lenalidomide to these treatments might help the immune system fight cancer. While the exact effectiveness of lenalidomide with rituximab and chemotherapy in this specific situation remains unknown, earlier research supports its safety when used with these drugs.

Overall, this treatment has been tested in people and is generally well-tolerated, with manageable side effects. However, since everyone reacts differently, potential participants should discuss specific risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a potentially improved approach to battling lymphoma. Unlike the standard of care, which typically includes chemotherapy drugs like cyclophosphamide, doxorubicin, vincristine, and prednisone, Arm A of this trial adds lenalidomide to the mix. Lenalidomide is an immunomodulatory agent that might boost the immune system’s ability to fight cancer and potentially enhance the effectiveness of the existing chemotherapy regimen. This combination could provide a more comprehensive attack on lymphoma cells, potentially leading to better outcomes for patients.

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

Previous studies have shown that combining rituximab with chemotherapy effectively treats certain types of lymphoma. This combination stops cancer cells from growing and spreading. In this trial, some participants will receive rituximab with chemotherapy alone, while others will receive an additional treatment with lenalidomide. Lenalidomide may strengthen the immune system and has shown promise when added to this treatment for aggressive lymphomas. Early research suggests that lenalidomide can be safely used with rituximab and chemotherapy, possibly leading to better outcomes. These combinations might improve results against diffuse large B cell lymphoma. ^{1 6 7 8 9}

Who Is on the Research Team?

Grzegorz S Nowakowski

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed stage II-IV diffuse large B cell lymphoma. Participants must have a performance status of 0-2, meaning they can perform daily activities without significant limitations. They should not have had previous treatments for lymphoma or other active cancers requiring therapy, no history of heart issues like recent myocardial infarction, and be able to take blood thinners if necessary.

Inclusion Criteria

I have a tumor tissue sample from my initial biopsy ready for analysis.

I am willing and able to take blood thinning medication as prescribed.

I do not have AIDS or conditions related to it, and if HIV positive, I am on certain antiretrovirals with a CD4 count over 400.

Exclusion Criteria

Patient is living outside the US

I have had a condition where my lymphocytes grow abnormally.

I have a history of cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive rituximab and combination chemotherapy with or without lenalidomide every 21 days for 6 courses

18 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

Every 3 months for 2 years, every 6 months for 1 year, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Doxorubicin Hydrochloride
• Lenalidomide
• Prednisone
• Rituximab
• Vincristine Sulfate

Trial Overview The study is testing the effectiveness of rituximab combined with chemotherapy drugs (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone) versus the same combination with an additional drug called lenalidomide. The goal is to see which regimen works better at treating diffuse large B cell lymphoma.

How Is the Trial Designed?

Group I: Arm A (rituximab, combination chemotherapy, lenalidomide) Experimental Treatment 7 Interventions

Patients receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1; prednisone PO on days 1-5; and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Group II: Arm B (rituximab, combination chemotherapy) Active Control 6 Interventions

Patients receive rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone as in Arm A. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The CHOEA-7 chemotherapy regimen, which includes cyclophosphamide, doxorubicin, vincristine, etoposide, and ara-C, has shown excellent results in treating patients with CD 20-positive non-Hodgkin's lymphoma.

Adding rituximab to the CHOEA-7 regimen (RCHOEA-7) further enhances treatment efficacy, indicating a promising approach for improving outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Results of dose-intense, dose-impact weekly combination chemotherapy with rituximab for patients with CD 20-positive B-cell non-Hodgkin's lymphoma]. Uzuka, Y., Saitou, Y., Saitou, K., et al.[2015]

In a study of 20 patients with untreated poor prognosis diffuse large B-cell lymphoma (DLBCL), the two-weekly dose-adjusted EPOCH-like chemotherapy (DA-EDOCH14-R) showed a promising three-year progression-free survival (PFS) rate of 95%, compared to 74% in a previous trial with a three-weekly regimen.

The treatment was well-tolerated with manageable toxicity and no therapy-related deaths, highlighting its safety, especially for patients with a high-risk prognosis (age-adjusted International Prognostic Index of 3), where PFS reached 100% compared to just 30% in the previous trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-weekly dose-adjusted (DA)-EPOCH-like chemotherapy with high-dose dexamethasone plus rituximab (DA-EDOCH14-R) in poor-prognostic untreated diffuse large B-cell lymphoma. García-Suárez, J., Flores, E., Callejas, M., et al.[2015]

In a study of 115 patients with Waldeyer's ring diffuse large B-cell lymphoma, those treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab (DA-EPOCH-R) showed significantly better progression-free survival (PFS) and overall survival (OS) compared to those receiving standard R-CHOP treatment, with 2-year PFS rates of 90.1% versus 80.5%.

The DA-EPOCH-R treatment was associated with fewer deaths (2 out of 42 patients) compared to R-CHOP (9 out of 42 patients) during a median follow-up of 45 months, while both treatments had similar clinical responses and treatment-related toxicities, indicating that DA-EPOCH-R is a safer and more effective option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-adjusted EPOCH-R vs. R-CHOP in frontline management of Waldeyer's ring diffuse large B-cell lymphoma: a retrospective study from a single institution. Liang, Y., Liu, X., Yang, J., et al.[2023]

Lenalidomide, when used in combination with rituximab, has been shown to be an effective treatment for patients with relapsed or refractory follicular lymphoma, offering a chemotherapy-free option.

This combination therapy improves outcomes compared to using rituximab alone and may serve as a viable alternative to traditional chemoimmunotherapy for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in follicular lymphoma. Flowers, CR., Leonard, JP., Fowler, NH.[2021]

In a phase 2 trial involving 80 patients with untreated high burden follicular lymphoma, the combination of lenalidomide and R-CHOP (R2-CHOP) resulted in a high complete response rate of 74% after six treatment cycles, indicating strong anti-cancer activity.

The treatment was generally safe, with the most common side effect being grade 4 neutropenia in 65% of patients, but no treatment-related deaths were reported, suggesting an acceptable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with R-CHOP (R2-CHOP) as first-line treatment of patients with high tumour burden follicular lymphoma: a single-arm, open-label, phase 2 study. Tilly, H., Morschhauser, F., Casasnovas, O., et al.[2019]

In the phase III AUGMENT trial, lenalidomide combined with rituximab significantly improved progression-free survival in patients with relapsed or refractory follicular lymphoma compared to placebo, showing particular benefit for elderly patients.

Lenalidomide has an acceptable safety profile, although it can cause more frequent cases of severe neutropenia, which can be managed with dosage adjustments and growth factor support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: A Review in Previously Treated Follicular Lymphoma. Blair, HA.[2021]

In a phase I study involving 21 elderly patients with untreated diffuse large B-cell lymphoma, the combination of lenalidomide and standard chemotherapy resulted in a high overall response rate of 90%, with 81% achieving complete remission.

The maximum tolerated dose of lenalidomide was determined to be 15 mg/day, with manageable safety concerns, including hematologic toxicities like neutropenia in 28% of treatment courses, indicating that this regimen is safe for elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide plus cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab is safe and effective in untreated, elderly patients with diffuse large B-cell lymphoma: a phase I study by the Fondazione Italiana Linfomi. Chiappella, A., Tucci, A., Castellino, A., et al.[2021]

In a study of 50 patients treated with R-CHOP-14 for aggressive B-cell lymphoma, 82% achieved a complete or improved response, indicating high efficacy of this treatment regimen.

Despite its effectiveness, R-CHOP-14 was associated with significant toxicities, including grade 3-4 neutropenia in 32% of patients and peripheral neuropathy in 45%, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with biweekly CHOP plus rituximab chemoimmunotherapy for the treatment of aggressive B-cell non-Hodgkin lymphoma. Aguiar Bujanda, D., Aguiar Morales, J., Bohn Sarmiento, U., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/23812930/

a phase I study by the Fondazione Italiana Linfomi Lenalidomide alone or in combination with rituximab has been shown to be active in relapsed/refractory aggressive lymphomas. In this phase I study we determined ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1805104

Rituximab plus Lenalidomide in Advanced Untreated ... Rituximab plus chemotherapy has been shown to be effective in patients with advanced-stage, previously untreated follicular lymphoma.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.20.01366

ROBUST: A Phase III Study of Lenalidomide Plus R-CHOP ... What is the potential improvement in outcomes with the combination of lenalidomide plus rituximab plus cyclophosphamide, doxorubicin, ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02340936

Study Details | NCT02340936 | Clinical Trial to ... A phase 1 study showed that lenalidomide can be safely combined with R-CHOP (R2CHOP) in the initial chemotherapy for aggressive B-cell lymphomas. Preliminary ...

5. ncoda.org ncoda.org/pes/rituximab-cyclophosphamide-doxorubicin-vincristine-and-prednisone/

Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, ... About this Treatment. The combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is used for certain types of lymphoma.

6. clinicaltrial.be clinicaltrial.be/en/details/12366?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Rituximab and Combination Chemotherapy With or Without ... Patients receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1; prednisone PO on days 1-5 ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02636322

NCT02636322 | Smart Start: A Phase II Study of Rituximab, ... This phase II trial studies how well giving rituximab, lenalidomide, and ibrutinib with chemotherapy works in treating patients with high-risk diffuse large ...

8. hemonc.org hemonc.org/wiki/Mantle_cell_lymphoma

Mantle cell lymphoma R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone. Example orders. Example orders for R-CHOP in lymphoma ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3286173/

Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and ... R-CHOP was more effective than CHOP, with results comparable with those of more intensive regimens. Keywords: Rituximab, CHOP, Large B-cell lymphoma, Primary ...