Glofitamab + Chemotherapy for Non-Hodgkin's Lymphoma

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for diffuse large B-cell lymphoma, a specific type of blood cancer that has not responded to previous treatments. Researchers aim to determine if adding glofitamab (an antibody therapy) to a chemotherapy regimen of rituximab, ifosfamide, carboplatin, and etoposide is safe and effective. Individuals with this type of lymphoma who have tried one line of treatment, including a specific antibody therapy, but still have active disease might be suitable candidates, especially if they are eligible for more intensive treatments like a stem cell transplant or CAR-T therapy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

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

A previous study found that glofitamab, part of the treatment being tested, was safe for patients with relapsed or hard-to-treat large B-cell lymphoma. Nearly half of the patients in that study saw their cancer respond to the treatment, and the side effects were manageable.

Rituximab, another drug in the treatment plan, has long been used to treat similar conditions. While most patients experience some side effects, 38% encounter more serious ones. Its use is well-documented, and it is generally considered safe.

Ifosfamide is also included in the study. Although effective, it may increase the risk of other cancers later on, so weighing this risk against its potential benefits is important.

Carboplatin's safety in this specific treatment combination remains unclear, but it is a common drug in cancer therapy. Its side effects vary in severity.

Etoposide, another part of the treatment, is well-tolerated, especially in older patients with aggressive non-Hodgkin lymphoma. It has been used in various treatments and is generally safe for most people.

Together, these drugs aim to offer a new treatment option, and the study seeks to confirm their safety when used in combination. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lymphoma?

Researchers are excited about the treatment combination involving glofitamab for Non-Hodgkin's Lymphoma because it introduces a novel mechanism of action. Unlike standard treatments that primarily rely on chemotherapy or monoclonal antibodies like rituximab, glofitamab is a bispecific antibody. This means it can simultaneously bind to cancer cells and T-cells, potentially enhancing the immune system's ability to target and destroy cancer cells more effectively. This dual-targeting approach could offer a powerful new option for patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL), who may not respond well to existing therapies.

What evidence suggests that this treatment might be an effective treatment for non-Hodgkin's lymphoma?

Research shows that glofitamab may help treat relapsed or hard-to-treat diffuse large B-cell lymphoma (DLBCL). Studies found that glofitamab, a special type of antibody targeting cancer cells, reduced cancer in 52% of patients, meaning more than half saw their cancer shrink. In this trial, participants will receive a combination of glofitamab with chemotherapy agents, including rituximab, ifosfamide, carboplatin, and etoposide (glofit-R-ICE). Early tests of glofitamab combined with chemotherapy showed promising results, suggesting it might work well with other treatments. However, many patients experienced serious side effects. Consulting healthcare professionals is important to understand the potential risks and benefits. ^{6 7 8 9 10}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2206913

Glofitamab for Relapsed or Refractory Diffuse Large B-Cell ... Glofitamab therapy was effective for DLBCL. More than half the patients had an adverse event of grade 3 or 4.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12334432/

Efficacy and safety of Glofitamab in patients with R/R ... Glofitamab, a CD20-directed CD3 T-cell engager, was recently FDA-approved after demonstrating a 52% overall response rate (ORR) and a 39% ...

3. ashpublications.org ashpublications.org/blood/article/146/15/1824/546454/Preclinical-advances-in-glofitamab-combinations-a

Preclinical advances in glofitamab combinations: a new ... Glofitamab combinations with chemotherapy and antibody-drug conjugates reveal strong synergy in preclinical humanized lymphoma models.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2473952924007195

Safety and efficacy of glofitamab for relapsed/refractory ... Glofitamab, a bispecific antibody targeting CD20 and CD3, is approved for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) ...

5. oncologynewscentral.com oncologynewscentral.com/drugs/info/fda-rejects-glofitamab-for-diffuse-large-b-cell-lymphoma-indication

FDA Rejects Glofitamab (Columvi) for Diffuse Large B-cell ... The U.S. Food and Drug Administration declined to approve glofitamab-gxbm (Columvi) plus chemotherapy for diffuse large B-cell lymphoma, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7768428/

Current Immunotherapy Approaches in Non-Hodgkin ... In this review, we recapitulate currently used immunotherapy modalities in NHL and discuss future perspectives of combinatorial immunotherapy strategies.

7. sciencedirect.com sciencedirect.com/science/article/pii/S0006497119833669

High-Dose Ara-C, Carboplatin, Etoposide, and Steroids ... The efficacy and safety of ACES are still unclear because clinical study on ACES regimen for lymphoma is limited. Therefore, we retrospectively ...

8. emedicine.medscape.com emedicine.medscape.com/article/203399-treatment

Non-Hodgkin Lymphoma (NHL) Treatment & Management Radiation therapy (2500-4000 cGy) produces a 10-year failure-free survival (FFS) rate of 50-60%, with an overall survival (OS) rate of 60-80%.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT00598169

Bortezomib, Ifosfamide, Carboplatin, and Etoposide, With ... PURPOSE: This clinical trial is studying giving bortezomib together with dexamethasone, ifosfamide, carboplatin, and etoposide to see how well it works with or ...

10. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/abs/10.1002/hon.3236

A phase II study of gemcitabine, carboplatin ... This study evaluated the efficacy and safety of salvage chemotherapy with gemcitabine, carboplatin, dexamethasone, and rituximab (GCD ± R) for Japanese patients