Glofitamab + R-CHOP for Diffuse Large B-Cell Lymphoma

Recruiting at 46 trial locations

Overseen By Reference Study ID Number: GO43075

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Hoffmann-La Roche

Disqualifiers: Gray-zone lymphoma, Burkitt, CNS lymphoma, 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: 30 weeks

46 Participants Needed

Trial Summary

What is the purpose of this trial?

This Phase II, open-label, multicenter study will evaluate the safety, efficacy, and pharmacokinetics of glofitamab in combination with rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in individuals with circulating tumor DNA (ctDNA) high-risk diffuse large B-cell lymphoma (DLBCL), as the first line of treatment.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you have had prior treatment for indolent lymphoma or have received certain therapies, you may not be eligible. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination Glofitamab + R-CHOP for treating diffuse large B-cell lymphoma?

Research shows that the addition of rituximab to the R-CHOP chemotherapy regimen improves outcomes for patients with diffuse large B-cell lymphoma. R-CHOP, which includes drugs like cyclophosphamide, doxorubicin, vincristine, and prednisone, is a standard treatment for this condition, and the addition of rituximab has been shown to enhance its effectiveness. ^{1 2 3 4 5}

Is the combination of Glofitamab and R-CHOP generally safe for humans?

The R-CHOP regimen, which includes drugs like rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, is known to cause some side effects, such as febrile neutropenia (a fever with low white blood cell count) and non-neutropenic fever (a fever without low white blood cell count). However, studies have shown that the safety profile of R-CHOP is generally acceptable, with no treatment-related deaths reported in some trials. The safety of Glofitamab in combination with R-CHOP specifically may not be fully established, but the existing data on R-CHOP provides some reassurance about its general safety in humans. ^{6 7 8 9 10}

How is the drug Glofitamab + R-CHOP different from other treatments for diffuse large B-cell lymphoma?

Glofitamab + R-CHOP is unique because it combines a novel drug, Glofitamab, with the standard R-CHOP regimen, potentially offering a new mechanism of action by targeting specific proteins on cancer cells, which may enhance treatment effectiveness compared to traditional R-CHOP alone. ^{1 5 7 11 12}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for patients with untreated CD20-positive Diffuse Large B-Cell Lymphoma (DLBCL) who are at high risk based on circulating tumor DNA. They should have a good performance status, measurable lymphoma lesions, normal heart function, and adequate blood cell counts. Pregnant or breastfeeding individuals and those with certain other lymphomas or prior treatments are excluded.

Inclusion Criteria

Life expectancy of at least 6 months

I can take care of myself and am up and about more than half of my waking hours.

My blood cell counts are within a healthy range.

Exclusion Criteria

I have had a solid organ or bone marrow transplant.

I have received treatment for a slow-growing type of lymphoma.

I am allergic or cannot take part of the R-CHOP chemotherapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive glofitamab in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as the first line of treatment

30 weeks

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Cyclophosphamide
• Doxorubicin
• Glofitamab
• Prednisone
• Rituximab
• Tocilizumab
• Vincristine

Trial Overview The study tests the combination of Glofitamab and Rituximab with CHOP chemotherapy in high-risk DLBCL patients as a first treatment. It's an open-label Phase II trial to assess safety, effectiveness, and how the body processes these drugs.

Participant Groups

Group I: Glofitamab + R-CHOP Immunochemotherapy Experimental Treatment 7 Interventions

Participants will receive step-up doses of glofitamab, starting on Day 8 of Cycle 3 (2.5 mg), Day 15 of Cycle 3 (10 mg), then 30 mg glofitamab will be given every three weeks (Q3W) onwards, on Day 8 of Cycles 4-6 and on Day 1 of Cycles 7-10. (cycle length = 21 days) Participants will receive rituximab, cyclophosphamide, doxorubicin, and vincristine Q3W on Day 1 of Cycles 1-6. Prednisone or prednisolone will be administered daily (QD) on Days 1-5 of Cycles 1-6. (cycle length = 21 days)

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?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Findings from Research

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 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]

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 involving 602 elderly patients with untreated diffuse large B-cell lymphoma, the dose-dense R-CHOP regimen administered every 2 weeks (R-CHOP14) did not show improved event-free survival compared to the standard 3-week schedule (R-CHOP21), with 3-year event-free survival rates of 56% and 60% respectively.

Although both regimens had similar rates of serious adverse events, the R-CHOP14 group experienced a significantly higher need for red-blood-cell transfusions (47% vs. 31% in R-CHOP21), indicating a potential drawback of the more frequent dosing schedule.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): a randomised phase 3 trial. Delarue, R., Tilly, H., Mounier, N., et al.[2022]

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 397 newly diagnosed diffuse large B-cell lymphoma patients treated with R-CHOP, non-neutropenic fever (NNF) occurred in 9.8% of patients, primarily after the third cycle, with interstitial pneumonitis being the most common cause.

NNF was associated with a higher mortality rate of 10.3% compared to febrile neutropenia (FN), which had a mortality rate of only 1.3%, highlighting the need for careful monitoring and management of febrile complications during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Significance of Non-neutropenic Fever in the Management of Diffuse Large B-Cell Lymphoma Patients Treated with Rituximab-CHOP: Comparison with Febrile Neutropenia and Risk Factor Analysis. Park, S., Kang, CI., Chung, DR., et al.[2018]

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]

In a study of 23 patients with aggressive B-cell non-Hodgkin lymphoma, the combination of rituximab with CODOX-M/IVAC showed promising efficacy, with 83% of low-risk and 71% of high-risk patients achieving complete remission after treatment.

The safety profile was acceptable, with no treatment-related deaths and manageable toxicity, including only two cases of grade 3 neutropenia, suggesting that this treatment combination is both effective and safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in combination with CODOX-M/IVAC: a retrospective analysis of 23 cases of non-HIV related B-cell non-Hodgkin lymphoma with proliferation index >95%. Mohamedbhai, SG., Sibson, K., Marafioti, T., 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 phase III study involving 300 patients with untreated indolent B-cell lymphoma, the R-CHOP-14 regimen (administered every 2 weeks) did not significantly improve progression-free survival (PFS) compared to the standard R-CHOP-21 regimen (every 3 weeks), with median PFS times of 4.7 years and 3.7 years respectively.

While both treatment regimens showed similar overall survival rates (approximately 87% to 88% at 6 years), the R-CHOP-21 group experienced more severe side effects, such as grade 4 neutropenia and grade 3 infections, indicating that the dose-dense strategy did not enhance efficacy and may have increased toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II/III study of R-CHOP-21 versus R-CHOP-14 for untreated indolent B-cell non-Hodgkin's lymphoma: JCOG 0203 trial. Watanabe, T., Tobinai, K., Shibata, T., et al.[2022]

In a retrospective analysis of 371 high-risk DLBCL patients, adding rituximab to standard chemotherapy (R-CHOP) significantly improved overall response rates (ORR) from 76.7% to 95.6% (P <0.05).

R-CHOP with rituximab also enhanced 5-year overall survival (OS) and progression-free survival (PFS) in both younger and older patients, with younger patients showing OS of 42% vs 38% and PFS of 46% vs 27%, and older patients showing OS of 82% vs 52% and PFS of 67% vs 45% (all P <0.05).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of rituximab in the first-line therapy of high-risk diffuse large B-cell lymphoma: a retrospective analysis by the Polish Lymphoma Research Group. Jurczak, W., Ochrem, B., Giza, A., et al.[2019]

References

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

Nursing Alchemy: Transforming R-CHOP Information Into Essentials. [2023]

2. England 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). [2022]

3. 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]

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

Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): a randomised phase 3 trial. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

Phase II study of CHOP-GR therapy in diffuse large B-cell lymphoma. [2021]

6. Greece pubmed.ncbi.nlm.nih.gov

Evaluation of Medication Instruction Sheets for Patients Undergoing R-CHOP Therapy in Non-Hodgkin's Lymphoma. [2022]

7. Korea (South) pubmed.ncbi.nlm.nih.gov

Clinical Significance of Non-neutropenic Fever in the Management of Diffuse Large B-Cell Lymphoma Patients Treated with Rituximab-CHOP: Comparison with Febrile Neutropenia and Risk Factor Analysis. [2018]

8. England pubmed.ncbi.nlm.nih.gov

A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Rituximab in combination with CODOX-M/IVAC: a retrospective analysis of 23 cases of non-HIV related B-cell non-Hodgkin lymphoma with proliferation index >95%. [2015]

10. United States 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. [2022]

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

Phase II/III study of R-CHOP-21 versus R-CHOP-14 for untreated indolent B-cell non-Hodgkin's lymphoma: JCOG 0203 trial. [2022]

12. Poland pubmed.ncbi.nlm.nih.gov

Role of rituximab in the first-line therapy of high-risk diffuse large B-cell lymphoma: a retrospective analysis by the Polish Lymphoma Research Group. [2019]