Rituximab + Chemotherapy for B-Cell Lymphoma

Recruiting at 1 trial location

Overseen By Research Nurse Navigator

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Jennifer Amengual

Must be taking: Rituximab

Disqualifiers: Systemic chemotherapy, CNS involvement, 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: 4

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that participants must not have had chemotherapy for other conditions within 4 weeks before starting the study.

What data supports the effectiveness of the drug combination Rituximab + Chemotherapy for B-Cell Lymphoma?

Research shows that adding rituximab to the CHOP chemotherapy regimen (which includes cyclophosphamide, doxorubicin, vincristine, and prednisone) improves outcomes for patients with aggressive B-cell lymphoma. This combination, known as R-CHOP, has been shown to be effective in treating various types of B-cell lymphomas. ^{1 2 3 4 5}

Is Rituximab with Chemotherapy safe for B-Cell Lymphoma?

Rituximab combined with chemotherapy drugs like cyclophosphamide, doxorubicin, vincristine, and prednisone has been studied for safety in various types of B-cell lymphoma. Some studies have reported adverse effects such as vomiting and drug hypersensitivity, but these treatments are generally considered safe for use in humans. ^{3 6 7 8 9}

How is the drug Rituximab + Chemotherapy unique for treating B-cell lymphoma?

Rituximab combined with chemotherapy, including cyclophosphamide, doxorubicin, etoposide, prednisone, and vincristine, is unique because it has shown the highest efficacy in treating diffuse large B-cell lymphoma and follicular lymphoma, with high activity and low toxicity compared to other treatments. ^{2 7 10 11 12}

What is the purpose of this trial?

The purpose of this study is to find out if there is a benefit to giving rituximab with etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (R-EPOCH) in participants who have high-risk B-cell PTLD in their 2nd phase of treatment (consolidation) while those with low-risk disease will be spared of chemotherapy and treated with rituximab consolidation alone. This study is also being done to find out about the usefulness of circulating tumor DNA (ctDNA), a novel blood test which, has been shown to help guide treatment decisions in other types of lymphoma. The goal is to answer the question if ctDNA is a viable and informative tool in treating PTLD with the hope that in the future it may be used to individualize study treatment for participants with PTLD in a way that limits study treatment toxicity without losing the effectiveness of the treatment plan.

Research Team

Jennifer Amengual, MD

Principal Investigator

Columbia University

Eligibility Criteria

This trial is for individuals with high-risk B-cell PTLD who are in their second phase of treatment. It's also suitable for those with low-risk disease, as they will receive a less intense therapy. Participants must have specific types of lymphoma or lymphoproliferative disorders to join.

Inclusion Criteria

I am 15 years old or older.

My lab tests show I can safely receive rituximab and R-EPOCH treatment.

Women of childbearing age must have a documented negative serum β-hCG measured within 2 weeks of starting treatment

Exclusion Criteria

I have had chemotherapy for post-transplant lymphoproliferative disorder.

My lymphoma has spread to my brain or spinal cord.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Participants receive induction therapy with rituximab to assess response and stratify into risk groups

Up to 3 years

Consolidation Therapy

Low-risk participants receive rituximab every 21 days for 4 cycles; high-risk participants receive R-EPOCH every 21 days for 4 cycles

12 weeks

4 cycles, each with multiple visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Treatment Details

Interventions

• Cyclophosphamide
• Doxorubicin
• Etoposide
• Prednisone
• Rituximab
• Vincristine

Trial Overview The study tests the effectiveness of combining rituximab with chemotherapy (R-EPOCH) against rituximab alone in treating PTLD. Additionally, it evaluates the use of ctDNA blood tests to guide treatment decisions and potentially personalize future therapies.

Participant Groups

Group I: Arm B (High-risk) Experimental Treatment 7 Interventions

Following completion of induction therapy, participants will be assigned to Arm B if they meet the following criteria: 1. Stable disease 2. Progressive disease OR 3. Partial response to rituximab induction with any of the following: * Residual bulky disease, defined as any single lesion measuring ≥ 7 cm or any 3 lesions each measuring ≥ 3 cm * High risk cytogenetic features including a complex karyotype (defined as ≥3 abnormalities on conventional karyotype), FISH positive for MYC rearrangement, double hit lymphoma (defined as MYC rearranged with BCL2 or BCL6), or p53 derangements * Plasmablastoid histology High-risk participants will receive R-EPOCH every 21 days for 4 cycles: * Rituximab 375 mg/m2 IV Day 1 * Etoposide 50 mg/m2 IV Day 1, 2, 3, 4 * Prednisone 60 mg/m2 PO Day 1, 2, 3, 4, 5 * Vincristine 0.4 mg/m2 IV Day 1, 2, 3, 4 * Cyclophosphamide 375 mg/m2 IV Day 5 * Doxorubicin 10 mg/m2 IV Day 1, 2, 3, 4

Group II: Arm A (Low-risk) Experimental Treatment 2 Interventions

Following completion of induction therapy, participants will be assigned to Arm A if they meet the following criteria: 1. Complete response to rituximab induction OR 2. Partial response to rituximab induction without any additional high-risk features. Low-risk participants will receive IV rituximab 375 mg/m2 every 21 days for 4 cycles.

Who Is Running the Clinical Trial?

Jennifer Amengual

Lead Sponsor

Trials

3

Recruited

80+

The Leukemia and Lymphoma Society

Collaborator

Trials

87

Recruited

26,200+

Findings from Research

In a study involving 549 patients with advanced indolent lymphoma, bendamustine plus rituximab significantly improved median progression-free survival (69.5 months) compared to R-CHOP (31.2 months), indicating it may be a more effective first-line treatment.

Bendamustine plus rituximab was better tolerated than R-CHOP, with significantly lower rates of side effects such as alopecia, hematological toxicity, infections, and peripheral neuropathy, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Rummel, MJ., Niederle, N., Maschmeyer, G., et al.[2022]

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]

In a study of 824 young patients with good-prognosis diffuse large-B-cell lymphoma, adding rituximab to CHOP-like chemotherapy significantly improved 3-year event-free survival (79% vs 59%) and overall survival (93% vs 84%).

The study identified two prognostic subgroups based on treatment response and disease characteristics, allowing for a more tailored therapeutic approach without increasing the frequency of adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Pfreundschuh, M., Trümper, L., Osterborg, A., et al.[2022]

In a study of 435 patients with diffuse large B-cell lymphoma (DLBCL), the addition of rituximab to CHOP chemotherapy (R-CHOP) was associated with a reduced risk of central nervous system (CNS) relapse, showing a trend of 6.4% risk in R-CHOP patients compared to 9.7% in those treated with CHOP.

Rituximab significantly lowered the risk of CNS relapse (hazard ratio 0.45) and this benefit was even greater for patients who achieved a complete response (hazard ratio 0.18), indicating that R-CHOP is particularly effective in preventing CNS involvement in DLBCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and risk factors for central nervous system relapse in patients with diffuse large B-cell lymphoma: the impact of the addition of rituximab to CHOP chemotherapy. Villa, D., Connors, JM., Shenkier, TN., et al.[2022]

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]

In a pooled analysis of 150 patients with HIV-associated aggressive B-cell non-Hodgkin lymphoma, those treated with R-EPOCH showed significantly better event-free survival (EFS) and overall survival (OS) compared to those receiving R-CHOP, particularly in patients with a CD4 count ≥100/μL.

Patients with CD4 counts <50/μL experienced a much higher rate of treatment-related deaths (37% vs 6%), indicating that lower immune function increases the risk of lethal toxicity during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled analysis of AIDS malignancy consortium trials evaluating rituximab plus CHOP or infusional EPOCH chemotherapy in HIV-associated non-Hodgkin lymphoma. Barta, SK., Lee, JY., Kaplan, LD., et al.[2022]

In a study of 13 elderly patients (median age 79) with diffuse large B cell lymphoma, the combination of rituximab with CHOP or THP-COP resulted in a 54% complete response rate and a 62% two-year survival rate, indicating its efficacy in this age group.

The treatment was generally safe, although 69% of patients experienced bone marrow suppression, and infusion reactions occurred in 30.7%, which were manageable by adjusting the rituximab dosage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The efficacy and adverse effects of rituximab with CHOP or THP-COP in old-old and extremely old patients with diffuse large B cell lymphoma]. Kikukawa, M., Miyazaki, K., Kiuchi, A., et al.[2019]

In a phase 3 study involving 447 treatment-naive patients with indolent non-Hodgkin's lymphoma or mantle cell lymphoma, bendamustine plus rituximab (BR) was found to be noninferior to standard rituximab-chemotherapy regimens (R-CHOP/R-CVP) in achieving complete response rates (31% vs 25%).

While BR showed a higher overall response rate (97% vs 91%), it also had a higher incidence of vomiting and drug-hypersensitivity reactions compared to standard therapies, indicating a need to consider safety profiles when choosing treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Flinn, IW., van der Jagt, R., Kahl, BS., et al.[2022]

Rituximab is a highly effective monoclonal antibody for treating various B-cell lymphomas, including follicular lymphoma and diffuse large B-cell lymphoma, demonstrating a strong activity with low toxicity.

The combination of rituximab with chemotherapy (R-CHOP) has shown the highest efficacy reported for any chemotherapy regimen in treating diffuse large B-cell lymphoma and follicular lymphoma, although some patients may still be resistant to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab therapy in malignant lymphoma. Coiffier, B.[2022]

Rituximab has revolutionized lymphoma treatment, showing effectiveness as a single agent in all types of B-cell lymphomas, both indolent and aggressive.

Combining rituximab with chemotherapy (like CHOP) significantly improves treatment outcomes for large-cell lymphomas without adding significant toxicity, establishing it as the standard of care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab and chemotherapy for aggressive lymphomas: a significant advance in therapy. Hagemeister, FB.[2015]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. [2022]

2. China pubmed.ncbi.nlm.nih.gov

[Efficacy of R±BEACOP regimen in patients with poor-prognosis lymphoma]. [2019]

3. Italy pubmed.ncbi.nlm.nih.gov

Clinical experience with biweekly CHOP plus rituximab chemoimmunotherapy for the treatment of aggressive B-cell non-Hodgkin lymphoma. [2021]

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

CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. [2022]

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

Incidence and risk factors for central nervous system relapse in patients with diffuse large B-cell lymphoma: the impact of the addition of rituximab to CHOP chemotherapy. [2022]

6. China 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. [2023]

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

Pooled analysis of AIDS malignancy consortium trials evaluating rituximab plus CHOP or infusional EPOCH chemotherapy in HIV-associated non-Hodgkin lymphoma. [2022]

8. Japan pubmed.ncbi.nlm.nih.gov

[The efficacy and adverse effects of rituximab with CHOP or THP-COP in old-old and extremely old patients with diffuse large B cell lymphoma]. [2019]

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

Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. [2022]

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

Rituximab therapy in malignant lymphoma. [2022]

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

Rituximab and chemotherapy for aggressive lymphomas: a significant advance in therapy. [2015]

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

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