Split-Dose R-CHOP for Lymphoma

Overseen By Cancer Connect

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Wisconsin, Madison

Must be taking: Entecavir

Must not be taking: Investigational drugs

Disqualifiers: Anthracycline exposure, 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: 12

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new schedule for administering the R-CHOP chemotherapy regimen to treat Diffuse Large B-Cell Lymphoma (DLBCL), with a focus on elderly patients. Researchers aim to determine if this split-dose approach is effective and safer for those aged 75 and older, a group often excluded from other trials. Participants should have a recent DLBCL diagnosis and must not have started treatment. The trial will last about 2.5 years. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to potentially safer treatment options for their age group.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have hepatitis B, you will need to take entecavir as part of the trial requirements.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that the R-CHOP treatment, which combines rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, is commonly used to treat Diffuse Large B-Cell Lymphoma (DLBCL). Studies have found that this treatment cures about 70% of patients with DLBCL. However, increasing the frequency of doses does not improve results and can cause more side effects.

A study on a split-dose schedule of R-CHOP for older adults has provided some insights. Split-dosing divides the treatment into two parts over a cycle, which can help manage side effects better. Results from previous patients suggest that this approach might be easier for older patients to handle, though potential side effects remain a consideration.

For those considering joining a trial, it is reassuring to know that R-CHOP is a well-established treatment with a known safety record. This study is simply testing a new way to schedule the doses. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the split-dose R-CHOP regimen for lymphoma because it modifies the standard R-CHOP treatment by splitting the chemotherapy doses, potentially enhancing its effectiveness. Traditionally, R-CHOP is administered in a single session per cycle, but this split-dose approach divides the treatment into two parts within a 28-day cycle, which might reduce side effects and improve patient tolerance. Additionally, this method could maintain or even increase the treatment's effectiveness by sustaining drug exposure over a longer period, offering hope for improved outcomes in lymphoma management.

What evidence suggests that this split-dose R-CHOP treatment could be effective for Diffuse Large B-Cell Lymphoma?

Research has shown that R-CHOP, a combination of chemotherapy drugs, is effective for about 70% of patients with Diffuse Large B-Cell Lymphoma (DLBCL). This treatment includes rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. Studies have found that administering R-CHOP more frequently does not enhance its effectiveness but can increase side effects. This trial tests a split-dose R-CHOP for older patients to determine if it remains effective while reducing side effects. The goal is to identify a safe and effective treatment for older patients, who are often excluded from trials due to age-related risks. Early results from similar treatments have been encouraging, showing good survival rates. ^{1 2 3 5 6}

Who Is on the Research Team?

Christopher Fletcher, MD

Principal Investigator

University of Wisconsin, Madison

Nirav Shah, MD, MS

Principal Investigator

Medical College of Wisconsin Clinical Cancer Center

Are You a Good Fit for This Trial?

This trial is for older adults aged 75+ with untreated Diffuse Large B-Cell Lymphoma (DLBCL). Some individuals aged 70-74 may qualify if they are unfit or frail. Participants must have a good heart function, no severe liver issues, and not be HIV positive. Prior low-grade NHL treatment without anthracyclines is okay. Exclusions include recent heart attack, CNS involvement by lymphoma, very poor kidney function, active second cancer within the last two years, and certain infections.

Inclusion Criteria

Negative HIV test

I have hepatitis C antibodies but my viral load is negative.

I have hepatitis B but my viral load is negative and I'm following a prevention plan during chemotherapy.

Exclusion Criteria

I have had cancer before, but I haven't needed chemotherapy for it in the last 2 years.

My cancer has spread to my brain or its coverings.

I do not have any active, uncontrolled infections.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive split-dose R-CHOP chemotherapy for up to 6 months, with Rituximab on Day 1 and CHOP chemotherapy on Days 1 and 15 of each 28-day cycle

6 months

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cancer-specific geriatric assessments

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Doxorubicin
• Prednisone
• Rituximab
• Vincristine

Trial Overview The study tests a split-dose R-CHOP chemotherapy regimen in elderly patients with DLBCL to see if it's effective and tolerable. R-CHOP includes Rituximab plus four other drugs: Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone. The trial lasts for about 2.5 years including follow-up after six months of treatment.

How Is the Trial Designed?

Group I: Split Dose R-CHOP Experimental Treatment 6 Interventions

Each cycle is 28 days and consists of one "A" treatment on Day 1 and one "B" treatment on Day 15 for 6 cycles Day 1 ("A" part of cycle) * Rituximab 375 mg/m2 IV (or biosimilars Ruxience or Truxima) * Cyclophosphamide 375 mg/m2 IV * Doxorubicin 25 mg/m2 IV * Vincristine 1 mg IV * Prednisone 50 mg (Days 1-5) PO * Pegfilgrastim (supportive care) 6 mg on Day 2 (24 hours after completion of chemotherapy) or filgrastim daily as institutionally indicated (starting 24 hours post completion of chemotherapy), or institutional standard granulocyte stimulating factor. Day 15 ("B" part of cycle) * Cyclophosphamide 375 mg/m2 IV * Doxorubicin 25 mg/m2 IV * Vincristine 1 mg IV * Prednisone 50 mg (Days 15-19) PO * Pegfilgrastim (supportive care) 6 mg on Day 16 (24 hours after completion of chemotherapy) or filgrastim daily as institutionally indicated (starting 24 hours post completion of chemotherapy), or institutional standard granulocyte stimulating factor.

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?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

Medical College of Wisconsin

Collaborator

Trials

645

Recruited

1,180,000+

Published Research Related to This Trial

The R-CHOP regimen, which includes rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, is a standard first-line treatment for diffuse large B-cell lymphoma, highlighting its importance in oncology.

Nursing implications of administering R-CHOP are significant, as the combination of these drugs requires careful monitoring for side effects and patient management during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nursing Alchemy: Transforming R-CHOP Information Into Essentials. Sakowski, AK., Patel, PR.[2023]

In a study of 582 patients with diffuse large B-cell lymphoma (DLBCL) treated in Germany, both R-CHOP-14 and R-CHOP-21 regimens showed similar overall survival rates at 3 years, with 84% for R-CHOP-14 and 84% for R-CHOP-21.

The findings confirm previous randomized clinical trials that indicated no superiority of the dose-dense R-CHOP-14 over the standard R-CHOP-21, supporting the use of either regimen in routine clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Similar effectiveness of R-CHOP-14 and -21 in diffuse large B-cell lymphoma-data from the prospective German Tumour Registry Lymphatic Neoplasms. Knauf, W., Abenhardt, W., Mohm, J., et al.[2020]

The medication instruction sheet (MIS) developed for patients receiving R-CHOP therapy effectively predicted 71% of adverse drug reactions (ADRs) during the treatment period, demonstrating its usefulness in managing these reactions.

The MIS accurately matched the onset timing of infusion reactions and peripheral neuropathy, although its effectiveness was lower for predicting thrombocytopenia-related ADRs, indicating areas for improvement in monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Medication Instruction Sheets for Patients Undergoing R-CHOP Therapy in Non-Hodgkin's Lymphoma. Uchida, M., Kawai, R., Hisamitsu, R., 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 112 patients under 65 years old with diffuse large B-cell lymphoma, the combination of rituximab and high-dose sequential chemotherapy led to an impressive 80% clinical remission rate, demonstrating its efficacy in treating this aggressive cancer.

At a median follow-up of 48 months, 78% of patients remained alive and 73% were in continuous remission, indicating that this treatment significantly improves life expectancy compared to conventional chemotherapy for younger patients with higher risk scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged survival in poor-risk diffuse large B-cell lymphoma following front-line treatment with rituximab-supplemented, early-intensified chemotherapy with multiple autologous hematopoietic stem cell support: a multicenter study by GITIL (Gruppo Italiano Terapie Innovative nei Linfomi). Tarella, C., Zanni, M., Di Nicola, M., et al.[2022]

The AMOPLACE chemotherapy regimen, which includes additional agents beyond the standard CHOP treatment, achieved a complete response rate of 68% in 60 patients with intermediate to high-grade non-Hodgkin's lymphomas, indicating its potential efficacy.

Despite its effectiveness, AMOPLACE was associated with significant myelosuppression, as 73% of patients experienced low white blood cell counts, and there were two treatment-related deaths, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AMOPLACE treatment of intermediate-grade and high-grade malignant lymphoma: a Cancer and Leukemia Group B study. Parker, BA., Santarelli, M., Green, MR., et al.[2017]

In a study of 250 patients with indolent non-Hodgkin lymphomas, both R-CVP and R-CHOP regimens followed by rituximab maintenance showed similar efficacy in terms of event-free survival and progression-free survival after a median follow-up of over 5 years.

R-CVP demonstrated significantly lower rates of severe adverse events compared to R-CHOP, making it a safer option for induction treatment in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line R-CVP versus R-CHOP induction immunochemotherapy for indolent lymphoma with rituximab maintenance. A multicentre, phase III randomized study by the Polish Lymphoma Research Group PLRG4. Walewski, J., Paszkiewicz-Kozik, E., Michalski, W., et al.[2020]

In a study involving 166 patients with aggressive B-cell lymphoma, the addition of radiotherapy (RT) to the standard R-CHOP treatment significantly improved event-free survival (EFS) for those with bulky disease, indicating that RT is beneficial for this patient group.

Patients who did not receive RT had a higher risk of disease progression and lower overall survival rates, suggesting that RT effectively mitigates the risks associated with bulky disease in elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of radiotherapy to bulky disease in elderly patients with aggressive B-cell lymphoma. Held, G., Murawski, N., Ziepert, M., et al.[2022]

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]

The combination of biweekly THP-COP chemotherapy and radiotherapy resulted in a high 5-year overall survival rate of 89% and a cause-specific survival rate of 90% in 41 patients with early-stage non-Hodgkin's lymphoma.

Despite some patients experiencing grade 4 neutropenia (12%), the treatment was well-tolerated, with 93% of patients completing the chemotherapy as scheduled, indicating that this regimen is both feasible and effective for low-risk cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of modified version of CHOP plus radiotherapy for early-stage aggressive non-Hodgkin's lymphoma of the head and neck. Nishioka, T., Tsuchiya, K., Nishioka, S., et al.[2015]

In a study of 40 patients with low-grade or follicular B-cell non-Hodgkin's lymphoma, the combination of Rituxan (Rituximab) and CHOP chemotherapy resulted in a high overall response rate of 95%, with 55% achieving complete remission.

The combination therapy showed promising safety, with common side effects being manageable, and it also indicated potential for clearing minimal residual disease, as evidenced by the conversion of the bcl-2 translocation from positive to negative in several patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. Czuczman, MS., Grillo-López, AJ., White, CA., et al.[2022]

In a study of 180 patients with aggressive non-Hodgkin's lymphoma, the use of dexrazoxane significantly reduced the risk of cardiac events and congestive heart failure (CHF) during treatment with the CHOP/R-CHOP regimen, with a 5-year cumulative risk of cardiac events dropping from 29% to 8% after its introduction.

Younger patients (under 60 years) also showed a lower risk of cardiac events, indicating that both dexrazoxane and age are important factors in protecting against the cardiotoxic effects of chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and risk-factors of CHOP/R-CHOP-related cardiotoxicity in patients with aggressive non-Hodgkin's lymphoma. Limat, S., Daguindau, E., Cahn, JY., et al.[2022]

A phase 3 study involving 407 treatment-naïve patients with diffuse large B-cell lymphoma demonstrated that HLX01, a biosimilar to rituximab, has comparable efficacy to the reference drug, with overall response rates of 94.1% for HLX01 and 92.8% for rituximab, falling within the pre-defined equivalence margin.

The safety profiles of HLX01 and rituximab were similar, with nearly identical rates of treatment-emergent adverse events (99.5% vs. 99.0%) and serious adverse events (34.0% vs. 32.5%), confirming that HLX01 is a safe alternative to rituximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma. Shi, Y., Song, Y., Qin, Y., et al.[2021]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.7554

Phase II trial of split-dose R-CHOP for older patients with ... Results: To date, 14 pts have completed tx. The median age was 81 years (73-88) and 57% (n = 8) were male. Most pts had stage 4 disease (n ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7970687/

Rituximab in combination with cyclophosphamide ... R-CHOP cures approximately 70% of DLBCL patients. Dose-dense regimens do not show a benefit in response and increase toxicity.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03943901

Split-Dose R-CHOP for Older Adults With DLBCL This study will test the efficacy of split-dose R-CHOP for the treatment of elderly patients with de novo diagnosis of DLBCL or transformed DLBCL. Split-dose R ...

4. ashpublications.org ashpublications.org/bloodadvances/article/5/4/984/475201/A-randomized-phase-2-3-study-of-R-CHOP-vs-CHOP

A randomized phase 2/3 study of R-CHOP vs CHOP ... Key Points. For untreated DLBCL, CHOP combined with dose-dense rituximab is not superior to standard R-CHOP.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2213048921000510

Outcomes of patients with double/triple expressor diffuse ... The survival rate among double/triple expressor lymphoma patients received R-DA-EPOCH was 82.8%, and 83.3% received R-CHOP.

6. onclive.com onclive.com/view/dr-shah-on-the-investigation-of-split-dose-r-chop-in-dlbcl

Dr Shah on the Investigation of Split-Dose R-CHOP in ... Shah, MD, discusses primary outcomes from a phase 2 trial investigating split-dose R-CHOP in older patients with diffuse large B-cell lymphoma.