Glofitamab + Gemcitabine + Oxaliplatin for Lymphoma

Recruiting at 19 trial locations

Overseen By Reference Study ID Number: GO45434 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Hoffmann-La Roche

Must not be taking: Monoclonal antibodies, Immunosuppressive drugs

Disqualifiers: CNS disease, Cardiovascular disease, Pulmonary disease, Infections, 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: Unknown

Duration: 12 weeks

100 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have had certain cancer treatments, like chemotherapy or immunotherapy, within 2 weeks before starting the study, and you should not be on systemic immunosuppressive medications within 4 weeks prior to the first dose.

What data supports the effectiveness of the drug combination Glofitamab, Gemcitabine, and Oxaliplatin for treating lymphoma?

Research shows that the combination of Gemcitabine and Oxaliplatin has been effective in treating relapsed or refractory aggressive lymphoma, with a 43% overall response rate and a 30% complete response rate. This suggests that these drugs can be effective in difficult-to-treat lymphoma cases. ^{1 2 3 4 5}

Is the combination of Glofitamab, Gemcitabine, and Oxaliplatin safe for humans?

Gemcitabine and Oxaliplatin, when used together with other drugs, have been associated with serious skin reactions like toxic epidermal necrolysis (TEN), which is a severe rash that can be life-threatening. Careful monitoring for skin-related side effects is important when these drugs are combined. ^{6 7 8 9 10}

What makes the drug combination of Glofitamab, Gemcitabine, and Oxaliplatin unique for treating lymphoma?

This treatment is unique because it combines Glofitamab, a novel antibody therapy, with Gemcitabine and Oxaliplatin, which have shown effectiveness in patients who have not responded to other chemotherapy regimens. This combination may offer a new option for patients with difficult-to-treat lymphoma. ^{1 2 3 4 11}

What is the purpose of this trial?

The main goal of this trial is to study the frequency and severity of cytokine release syndrome (CRS) in participants with diffuse large B-cell lymphoma (DLBCL) who are using a combination of glofitamab + gemcitabine + oxaliplatin (Glofit-GemOx) followed by glofitamab-only treatment.

Research Team

Study Director

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with Diffuse Large B-Cell Lymphoma (DLBCL) who have tried at least one systemic therapy and are not candidates for stem cell transplant. They should be relatively active (ECOG status 0, 1, or 2), have measurable cancer lesions, and good blood and kidney function. Exclusions include severe allergies to monoclonal antibodies, prior treatments with certain drugs listed, significant other diseases or conditions that could interfere with the study or pose risks.

Inclusion Criteria

I can take care of myself and am up and about more than half of the day.

I have a tumor that can be measured on a CT scan.

I have received at least one treatment for my condition.

Exclusion Criteria

My slow-growing cancer has changed into aggressive large B-cell lymphoma.

Prior enrollment in Study GO41943 (NCT04313608), GO41944 (STARGLO; NCT04408638), or Study GO44900 (NCT06624085)

My condition is primary mediastinal B-cell lymphoma.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive obinutuzumab pre-treatment, followed by glofitamab + gemcitabine + oxaliplatin, and then glofitamab monotherapy

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Gemcitabine
• Glofitamab
• Oxaliplatin

Trial Overview The trial tests how often and how severely patients experience cytokine release syndrome when treated with a combination of glofitamab + gemcitabine + oxaliplatin followed by only glofitamab. It aims to optimize this treatment regimen's safety profile in those with relapsed/refractory DLBCL.

Participant Groups

Group I: R/R DLBCL Experimental Treatment 4 Interventions

Participants with R/R DLBCL will receive obinutuzumab pre-treatment, followed by glofitamab + gemcitabine + oxaliplatin, followed by glofitamab monotherapy.

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 GEMOX regimen, combining gemcitabine and oxaliplatin, showed an overall response rate of 45.8% in 24 lymphoma patients who had previously failed multiple chemotherapy treatments, with some achieving long-term survival.

While the treatment was effective, it was associated with significant hematologic toxicity, including grade III or IV neutropenia in 59.3% of patients, indicating that while GEMOX can be beneficial, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety evaluation of gemcitabine combined with oxaliplatin in lymphoma patients after failure of multiple chemotherapy regimens]. Yang, J., Shi, Y., He, X., et al.[2014]

In a study of 62 patients with relapsed/refractory B-cell lymphoma, the combination of gemcitabine and oxaliplatin (GEMOX) showed an overall response rate of 57%, while adding rituximab (R-GEMOX) improved the response rate to 78%.

R-GEMOX demonstrated better failure-free survival (28% at 42 months) and overall survival (37% at 42 months) compared to GEMOX, indicating that the addition of rituximab enhances treatment efficacy, although both treatments had significant side effects like neutropenia and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term results of gemcitabine plus oxaliplatin with and without rituximab as salvage treatment for transplant-ineligible patients with refractory/relapsing B-cell lymphoma. Corazzelli, G., Capobianco, G., Arcamone, M., et al.[2022]

The GIDOX treatment regimen showed a 52% overall response rate in 27 patients with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma, with 15% achieving complete remission and 37% partial remission after three cycles.

Despite some significant toxicities, including grade 3 and 4 neutropenia and thrombocytopenia, GIDOX was generally well-tolerated, allowing 26% of patients to proceed to high-dose chemotherapy followed by autologous stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage therapy with gemcitabine, ifosfamide, dexamethasone, and oxaliplatin (GIDOX) for B-cell non-Hodgkin's lymphoma: a consortium for improving survival of lymphoma (CISL) trial. Park, BB., Kim, WS., Eom, HS., et al.[2022]

In a Phase I trial involving 10 patients with intermediate grade non-Hodgkin lymphoma (NHL), the combination of gemcitabine at 500 mg/m² with standard CHOP chemotherapy was found to be the maximum tolerated dose, showing a 71% survival rate at 2.5 years.

The study reported significant toxicities, particularly in the higher dose cohort (750 mg/m²), where three out of four patients experienced dose-limiting toxicities, highlighting the need for careful monitoring and potential dose adjustments in future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial examining addition of gemcitabine to CHOP in intermediate grade NHL. Reagan, JL., Rosmarin, A., Butera, JN., et al.[2022]

In a study of 44 patients with relapsed aggressive lymphoma, the Gemcitabine/Oxaliplatin (Gem-Ox) regimen, with or without rituximab, showed an overall response rate of 43% and a complete response rate of 30%, indicating its efficacy as a second-line treatment.

Despite its favorable toxicity profile compared to more aggressive inpatient regimens, the treatment was associated with significant hematological toxicity, including a 22% incidence of febrile neutropenia, and the median overall survival for patients remained low at 8 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome for patients with relapsed/refractory aggressive lymphoma treated with gemcitabine and oxaliplatin with or without rituximab; a retrospective, multicentre study. Dhanapal, V., Gunasekara, M., Lianwea, C., et al.[2022]

In a meta-analysis of 11,465 patients from 18 clinical trials, PD-1/PD-L1 inhibitors were found to significantly increase the risk of developing dermatologic adverse effects like rash and pruritus compared to chemotherapy, with relative risks of 1.84 and 3.74, respectively.

PD-1/PD-L1 inhibitors showed a lower risk of mucosal inflammation and alopecia compared to chemotherapy, indicating a distinct safety profile that differs from traditional cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of dermatologic and mucosal adverse events associated with PD-1/PD-L1 inhibitors in cancer patients: A meta-analysis of randomized controlled trials. Yang, W., Li, S., Yang, Q.[2021]

A patient with NK/T-cell lymphoma developed toxic epidermal necrolysis (TEN) after receiving a combination of sintilimab and P-GemOx chemotherapy, highlighting a serious risk associated with this treatment regimen.

This case emphasizes the need for careful monitoring of skin-related toxicities when using PD-1 inhibitors like sintilimab in combination with other chemotherapy agents, as TEN can occur rapidly and may be life-threatening.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxic epidermal necrolysis associated with chemoimmunotherapy for lymphoma: case report and literature review. Yang, W., Xu, X., Xia, D., et al.[2022]

The addition of immune checkpoint inhibitors to chemotherapy does not significantly increase the risk of high-grade hematological toxicities like anemia, thrombocytopenia, or neutropenia, based on a meta-analysis of 11 studies.

However, the combination treatment does lead to a significantly higher risk of high-grade diarrhea, indicating a specific area of concern for patients undergoing this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity patterns associated with chemotherapy/immune checkpoint inhibitor combinations: a meta-analysis. Abdel-Rahman, O.[2020]

Immune checkpoint inhibitor (ICI) combination therapy significantly improves objective response rates (ORR), disease control rates (DCR), progression-free survival (PFS), and overall survival (OS) in patients with advanced malignancies, based on a meta-analysis of 10 studies involving 2410 patients.

While ICI combination therapy shows enhanced efficacy compared to monotherapy, it is associated with a higher incidence of severe adverse events, including fatigue, nausea, and elevated liver enzymes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitor (ICI) combination therapy compared to monotherapy in advanced solid cancer: A systematic review. Ma, X., Zhang, Y., Wang, S., et al.[2021]

In a meta-analysis of 18 studies involving 5,649 patients with non-small cell lung cancer, first-line therapy using PD-1/PD-L1 inhibitors showed a significantly higher risk of treatment-related adverse events (trAEs) and immune-related adverse events (irAEs) compared to subsequent therapies, indicating a need for careful monitoring in initial treatments.

Despite the higher incidence of adverse events in first-line therapy, the types of trAEs and irAEs were largely similar across different therapy lines, suggesting that while the severity may differ, the overall spectrum of side effects remains consistent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of first and subsequent lines of PD-1/PD-L1 inhibitors monotherapy in non-small cell lung cancer patients: a meta-analysis. Yang, Y., Pang, P., Xie, Z., et al.[2022]

The combination of gemcitabine, dexamethasone, and cisplatin (GDP) showed a promising overall response rate of 49% in patients with recurrent or refractory non-Hodgkin lymphoma, with 16% achieving complete responses after two treatment cycles.

Despite some significant toxicities, such as grade 3 and 4 neutropenia in 33% and 39% of patients respectively, the GDP regimen can be safely administered to outpatients, allowing many patients to proceed to stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine, dexamethasone, and cisplatin in patients with recurrent or refractory aggressive histology B-cell non-Hodgkin lymphoma: a Phase II study by the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG). Crump, M., Baetz, T., Couban, S., et al.[2022]

References

1. China pubmed.ncbi.nlm.nih.gov

[Efficacy and safety evaluation of gemcitabine combined with oxaliplatin in lymphoma patients after failure of multiple chemotherapy regimens]. [2014]

2. Germany pubmed.ncbi.nlm.nih.gov

Long-term results of gemcitabine plus oxaliplatin with and without rituximab as salvage treatment for transplant-ineligible patients with refractory/relapsing B-cell lymphoma. [2022]

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

Salvage therapy with gemcitabine, ifosfamide, dexamethasone, and oxaliplatin (GIDOX) for B-cell non-Hodgkin's lymphoma: a consortium for improving survival of lymphoma (CISL) trial. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Phase I trial examining addition of gemcitabine to CHOP in intermediate grade NHL. [2022]

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

Outcome for patients with relapsed/refractory aggressive lymphoma treated with gemcitabine and oxaliplatin with or without rituximab; a retrospective, multicentre study. [2022]

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

Risk of dermatologic and mucosal adverse events associated with PD-1/PD-L1 inhibitors in cancer patients: A meta-analysis of randomized controlled trials. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Toxic epidermal necrolysis associated with chemoimmunotherapy for lymphoma: case report and literature review. [2022]

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

Toxicity patterns associated with chemotherapy/immune checkpoint inhibitor combinations: a meta-analysis. [2020]

9. Australia pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitor (ICI) combination therapy compared to monotherapy in advanced solid cancer: A systematic review. [2021]

10. China pubmed.ncbi.nlm.nih.gov

The safety of first and subsequent lines of PD-1/PD-L1 inhibitors monotherapy in non-small cell lung cancer patients: a meta-analysis. [2022]

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

Gemcitabine, dexamethasone, and cisplatin in patients with recurrent or refractory aggressive histology B-cell non-Hodgkin lymphoma: a Phase II study by the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG). [2022]