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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining rituximab (a type of immunotherapy) with chemotherapy is more effective for individuals with high-risk B-cell PTLD, a type of lymphoma, while those with low-risk will receive only rituximab. It will also investigate whether a new blood test, circulating tumor DNA (ctDNA), can guide treatment decisions for PTLD. Individuals diagnosed with CD20+ PTLD and who have measurable disease might be suitable for this study. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to significant findings.

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.

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

Studies have shown that rituximab, when used regularly, is generally well-tolerated. Research indicates that adding rituximab to chemotherapy improves outcomes in certain types of lymphoma, with no unexpected safety issues reported. This suggests successful use in similar conditions, indicating a positive safety profile.

Regarding the R-EPOCH regimen, which includes rituximab along with etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin, additional considerations arise. Research shows that this combination can be more taxing on the body compared to some other treatments. Some patients have experienced stronger side effects, but doctors generally manage these during treatment. Discuss any concerns with the medical team, as they can provide specific information based on individual health needs.

Overall, the treatments under study have been used in other situations, aiding in understanding their safety. However, individual experiences may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using rituximab with chemotherapy for B-cell lymphoma because it offers a tailored approach based on risk. For low-risk patients, rituximab alone is used after the initial response, aiming for effectiveness with minimal treatment burden. High-risk patients receive R-EPOCH, which combines rituximab with multiple chemotherapy agents to aggressively target persistent or complex disease features. This dual strategy allows for a more personalized treatment plan, potentially improving outcomes by matching therapy intensity to disease severity.

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

Studies have shown that rituximab effectively treats B-cell cancers, such as diffuse large B-cell lymphoma and Burkitt's lymphoma, with many patients responding positively. For individuals with B-cell non-Hodgkin lymphoma, ongoing rituximab treatment has significantly extended the time they live without disease progression. In this trial, participants in the high-risk arm will receive the R-EPOCH treatment plan, which includes rituximab and several chemotherapy drugs. This regimen has been very successful in treating large B-cell lymphomas, helping to halt disease progression. This combination aims to more effectively target and destroy cancer cells, particularly in high-risk patients. ^{1 3 6 7 8}

Who Is on the Research Team?

Jennifer Amengual, MD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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]

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]

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]

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 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]

Citations

1. eviq.org.au eviq.org.au/haematology-and-bmt/lymphoma/other-b-cell-lymphoma/783-da-r-epoch-dose-adjusted-rituximab-etoposide

783-DA-R-EPOCH (dose adjusted rituximab etoposide ... This study was designed to assess the efficacy and safety of an infusional DA-EPOCH (dose-adjusted etoposide/vincristine/doxorubicin/bolus cyclophosphamide/ ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9036549/

DA-R-EPOCH vs R-CHOP in DLBCL: How Do We Choose? The emerging molecular and prognostic characterization of diffuse large B-cell lymphoma (DLBCL) has challenged the rituximab, cyclophosphamide, doxorubicin, ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2152265025002344

Impact of Chemoimmunotherapy Sequencing on Treatment ... Our findings suggest delaying rituximab following EPOCH did not affect treatment outcomes and are associated with lower infusion reactions.

4. bccancer.bc.ca bccancer.bc.ca/chemotherapy-protocols-site/Documents/Lymphoma-Myeloma/LYEPOCHR_Protocol.pdf

Adjusted Etoposide, DOXOrubicin, vinCRIStine Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas: a pharmacodynamic approach with high efficacy. Blood 2002;99:2685-93. 4. Petrich et al.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07097363

Study Details | NCT07097363 | Epcoritamab With Dose ... Giving epcoritamab with EPOCH-R may be safe, tolerable, and effective in treating patients with aggressive B-cell non-Hodgkin lymphoma. Detailed Description.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30939090/

Dose-Adjusted EPOCH-R Compared With R-CHOP ... - PubMed In the 50303 study population, the more intensive, infusional DA-EPOCH-R was more toxic and did not improve PFS or OS compared with R-CHOP.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01092182

NCT01092182 | Phase II Study of Dose-Adjusted EPOCH- ... Two National Cancer Institute (NCI) phase II trials have used etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) chemotherapy with 1 or 2 ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa1214561

Dose-Adjusted EPOCH-Rituximab Therapy in Primary ... Efficacy and Safety of Rituximab plus Modified EPOCH (Etoposide, Vincristine, Doxorubicin, Carboplatin, and Prednisolone) for Transplant ...