Glofitamab + Chemotherapy for Non-Hodgkin's Lymphoma

Recruiting at 12 trial locations

Overseen By Reference Study ID Number: GO43693 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Hoffmann-La Roche

Must not be taking: Bispecific antibodies, Immunosuppressive medications

Disqualifiers: CNS disease, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 9 weeks

43 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called glofitamab combined with other cancer drugs in patients with a type of lymphoma that hasn't responded to previous treatments. The treatment works by helping the immune system attack cancer cells and using chemotherapy to kill or stop the growth of these cells.

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

The trial requires that you stop certain cancer treatments, like chemotherapy and immunotherapy, at least 2 weeks before starting the study. If you're on monoclonal antibodies for cancer, you need to stop them 4 weeks before. If you're taking corticosteroids, you must be on a stable dose of 30 mg/day or less for at least 4 weeks before starting the trial.

What data supports the effectiveness of the drug combination Glofitamab + Chemotherapy for Non-Hodgkin's Lymphoma?

The combination of rituximab with chemotherapy has shown improved outcomes in various types of lymphomas, such as increased progression-free survival in mantle cell lymphoma and improved response rates in diffuse large B-cell lymphoma. Additionally, the ICE regimen (ifosfamide, carboplatin, and etoposide) has been effective for patients with relapsed or refractory non-Hodgkin's lymphoma. ^{1 2 3 4 5}

What safety data exists for the combination of Glofitamab and chemotherapy drugs like Carboplatin, Ifosfamide, and Etoposide?

The combination of Carboplatin, Ifosfamide, and Etoposide has been studied in various trials, showing that the main safety concerns are myelosuppression (a decrease in bone marrow activity leading to fewer blood cells), including neutropenia (low white blood cell count) and thrombocytopenia (low platelet count). Other side effects include nausea, fatigue, and mild nerve damage, but these are generally manageable. ^{6 7 8 9 10}

What makes the Glofitamab + Chemotherapy treatment unique for non-Hodgkin's lymphoma?

This treatment is unique because it combines glofitamab, a novel antibody targeting CD20 on B cells, with a chemotherapy regimen that includes carboplatin, etoposide, ifosfamide, and rituximab, which are known for their effectiveness in relapsed or refractory cases. The combination aims to enhance the immune system's ability to fight cancer cells while using chemotherapy to reduce tumor size. ^{5 11 12 13 14}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for people with a type of cancer called diffuse large B-cell lymphoma that has come back or didn't respond after their first treatment. They must have had therapy before that included an anti-CD20 antibody and anthracycline, be healthy enough to consider more intense treatments like stem cell transplant or CAR-T therapy, and not have certain medical conditions.

Inclusion Criteria

Life expectancy ≥ 12 weeks

I am eligible for intense chemotherapy followed by stem cell or CAR-T therapy.

My cancer is a type of B-cell lymphoma confirmed by lab tests.

Exclusion Criteria

I have had a stem cell transplant from a donor.

I am on a stable dose of corticosteroids not exceeding 30 mg/day for at least 4 weeks.

I have or had a brain-related condition like stroke or epilepsy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive up to 3 cycles of glofitamab, rituximab, ifosfamide, carboplatin, and etoposide (glofit-R-ICE)

9 weeks

3 cycles of 21 days each

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2.5 years

Treatment Details

Interventions

• Carboplatin
• Etoposide
• Glofitamab
• Ifosfamide
• Rituximab

Trial Overview Researchers are testing how well Glofitamab works when given with Rituximab plus Ifosfamide, Carboplatin, and Etoposide in patients whose cancer returned or resisted the first line of treatment. The study will look at the drug's effects on the body and its safety.

Participant Groups

Group I: R/R DLBCL Experimental Treatment 7 Interventions

Participants will receive up to 3 21-day cycles of glofitamab, rituximab, ifosfamide, carboplatin, and etoposide (glofit-R-ICE).

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

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

Salvage chemotherapy followed by high-dose therapy and autologous stem cell transplantation is the standard treatment for relapsed diffuse large B-cell lymphoma, but the addition of rituximab has improved outcomes after first-line treatment and relapses.

The CORAL trial found no significant difference in response rates between two salvage regimens (R-ICE and R-DHAP), and identified that factors like early relapse and certain genetic markers significantly affect survival, indicating that over 70% of patients may not benefit from standard salvage therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there any role for transplantation in the rituximab era for diffuse large B-cell lymphoma? Gisselbrecht, C.[2022]

In a study of 91 people living with HIV and Burkitt lymphoma, adding rituximab to CODOX-M/IVAC chemotherapy did not increase severe treatment-related toxicities, indicating it is a safe option for this population.

The addition of rituximab significantly improved both overall survival (72% vs. 55%) and progression-free survival (81% vs. 55%) compared to chemotherapy alone, suggesting it enhances treatment efficacy without added risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adding rituximab to CODOX-M/IVAC chemotherapy in the treatment of HIV-associated Burkitt lymphoma is safe when used with concurrent combination antiretroviral therapy. Alwan, F., He, A., Montoto, S., et al.[2022]

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 43 patients with inoperable non-small cell lung cancer (NSCLC), the combination of carboplatin, ifosfamide, and etoposide resulted in a 40% objective response rate, indicating potential efficacy for this treatment regimen.

The treatment was generally well-tolerated, with myelosuppression being the main dose-limiting side effect, while serious issues like nephrotoxicity and neurotoxicity were not observed, suggesting a favorable safety profile for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-finding studies with carboplatin, ifosfamide, etoposide, and mesna in non-small cell lung cancer. van Zandwijk, N., ten Bokkel Huinink, WW., Wanders, J., et al.[2018]

The combination of paclitaxel and carboplatin demonstrated a 53.3% objective response rate in 15 patients with stage III B and IV non-small cell lung cancer (NSCLC), indicating moderate efficacy in treating advanced disease.

While the regimen was associated with significant myelosuppression, including grade 3-4 granulocytopenia in 18% of treatment courses, most toxicities were manageable and well tolerated, suggesting a favorable safety profile for this chemotherapy combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel and carboplatin in combination in the treatment of advanced non-small-cell lung cancer (NSCLC): a preliminary study. Ratanatharathorn, V., Jirajarus, M., Sirachainan, E., et al.[2015]

Rituximab is the first FDA-approved monoclonal antibody for cancer treatment, specifically targeting the CD20 antigen on B cells, and has shown efficacy in treating relapsed low-grade and follicular non-Hodgkin's lymphoma in multicenter studies.

The treatment is generally well-tolerated, with side effects mainly consisting of mild fevers and chills during the first infusion, and its low immunogenicity allows for potential future treatments without significant complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of rituximab, the new FDA-approved antibody. Leget, GA., Czuczman, MS.[2019]

Rituximab, when combined with chemotherapy (FCM), significantly improves response rates in patients with relapsed or refractory indolent non-Hodgkin's lymphoma, achieving an overall response rate of 83% compared to 58% with FCM alone, without increasing toxicity.

The combination therapy shows particularly strong results in follicular lymphoma (92% response rate) and mantle cell lymphoma (65% response rate), suggesting that rituximab enhances treatment efficacy in these subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab plus chemotherapy in follicular and mantle cell lymphomas. Hiddemann, W., Dreyling, M., Unterhalt, M.[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]

References

1. Italy pubmed.ncbi.nlm.nih.gov

The addition of rituximab to fludarabine and cyclophosphamide chemotherapy results in a significant improvement in overall survival in patients with newly diagnosed mantle cell lymphoma: results of a randomized UK National Cancer Research Institute trial. [2018]

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

Is there any role for transplantation in the rituximab era for diffuse large B-cell lymphoma? [2022]

3. England pubmed.ncbi.nlm.nih.gov

Adding rituximab to CODOX-M/IVAC chemotherapy in the treatment of HIV-associated Burkitt lymphoma is safe when used with concurrent combination antiretroviral therapy. [2022]

4. 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]

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

Ifosfamide, carboplatin, and etoposide: a highly effective cytoreduction and peripheral-blood progenitor-cell mobilization regimen for transplant-eligible patients with non-Hodgkin's lymphoma. [2017]

6. Germany pubmed.ncbi.nlm.nih.gov

A phase I trial of AUC-directed carboplatin with infusional doxorubicin and ifosfamide plus G-CSF in patients with advanced gynecologic malignancies. [2013]

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

Dose-finding studies with carboplatin, ifosfamide, etoposide, and mesna in non-small cell lung cancer. [2018]

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

Phase I study of escalating targeted doses of carboplatin combined with ifosfamide and etoposide in treatment of newly diagnosed pediatric solid tumors. [2019]

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

Phase I trial of carboplatin, paclitaxel, etoposide, and cyclophosphamide with granulocyte colony stimulating factor as first-line therapy for patients with advanced epithelial ovarian cancer. [2015]

10. Thailand pubmed.ncbi.nlm.nih.gov

Paclitaxel and carboplatin in combination in the treatment of advanced non-small-cell lung cancer (NSCLC): a preliminary study. [2015]

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

Use of rituximab, the new FDA-approved antibody. [2019]

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

Rituximab plus chemotherapy in follicular and mantle cell lymphomas. [2022]

13. Germany pubmed.ncbi.nlm.nih.gov

IEVM chemotherapy with rhGM-CSF support for aggressive non-Hodgkin's lymphomas: a pilot study. [2019]

14. 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]