Golcadomide + R-CHOP for B-Cell Lymphoma

(GOLSEEK-1 Trial)

Recruiting at 682 trial locations

Overseen By BMS Clinical Trials Contact Center www.BMSClinicalTrials.com

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Celgene

Disqualifiers: Other lymphoma subtypes, CNS involvement, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 cycles (approximately 18 weeks)

850 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how well a new drug, golcadomide, works with a common chemotherapy mix (R-CHOP) for treating high-risk large B-cell lymphoma, a type of blood cancer. It compares this combination to standard chemotherapy alone to determine if adding golcadomide improves outcomes. The trial seeks participants who have not yet been treated for certain types of large B-cell lymphoma and have a significant tumor size. Participants will be randomly assigned to receive either the experimental treatment or the standard one. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants the opportunity to contribute to a treatment that could soon become widely available.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that patients with aggressive B-cell lymphoma have tolerated the combination of golcadomide and R-CHOP well. This treatment has demonstrated high rates of long-lasting positive responses, benefiting patients over an extended period. Importantly, this combination did not cause any unexpected side effects. The standard R-CHOP treatment is generally safe and commonly used for B-cell lymphoma. Adding golcadomide has not significantly increased side effects. Overall, available research suggests that the treatment is generally safe for people. ^{1 2 3 4 5}

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

Researchers are excited about Golcadomide in combination with R-CHOP for B-cell lymphoma because it introduces a novel active ingredient, Golcadomide, which could enhance the effectiveness of the standard R-CHOP regimen. Unlike traditional treatments that rely solely on the R-CHOP components—Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone—Golcadomide may offer a new mechanism of action that targets cancer cells differently. This potential to improve patient outcomes by providing an additional line of attack against lymphoma cells is why this treatment is generating interest among researchers.

What evidence suggests that this trial's treatments could be effective for large B-cell lymphoma?

Research has shown that golcadomide, one of the treatments in this trial, shows promise when combined with R-CHOP chemotherapy for high-risk large B-cell lymphoma. Studies have found that this combination leads to high rates of metabolic responses, effectively fighting the cancer. Participants in this trial may receive golcadomide plus R-CHOP, which has demonstrated long-lasting responses in patients with aggressive B-cell lymphoma, keeping their cancer at bay longer. Golcadomide targets specific proteins that help cancer cells survive, making it a unique treatment option. Overall, evidence suggests that this combination could be a strong option for treating this type of lymphoma. ^{2 3 6 7 8}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for adults with a new diagnosis of high-risk large B-cell lymphoma, including several specific subtypes. Participants must have an IPI score indicating moderate to high risk and measurable disease by certain medical imaging criteria. They cannot join if they have other types of lymphoma, CNS involvement by the lymphoma, or any condition that could interfere with their participation.

Inclusion Criteria

My cancer can be measured by scans and shows up on PET or CT/MRI.

I have a specific type of large B-cell lymphoma that has not been treated before.

My cancer is at stage II, III, or IV according to the Ann Arbor classification.

Exclusion Criteria

My lymphoma is not one of the excluded types.

Any significant medical condition, active infection, laboratory abnormality, or psychiatric illness that would prevent participation

My lymphoma has spread to or is suspected to be in my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either golcadomide plus R-CHOP chemotherapy or placebo plus R-CHOP chemotherapy

6 cycles (approximately 18 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Doxorubicin
• Golcadomide
• Prednisone
• Rituximab
• Vincristine

Trial Overview

The study is testing the effectiveness and safety of Golcadomide combined with R-CHOP chemotherapy versus a placebo combined with R-CHOP in treating patients who haven't been treated before for high-risk large B-cell lymphoma.

How Is the Trial Designed?

Group I: Golcadomide + R-CHOP (Rituximab, Doxorubicin, Vincristine, Cyclophosphamide, Prednisone) Experimental Treatment 6 Interventions

Group II: Placebo + R-CHOP Placebo Group 6 Interventions

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?

Celgene

Lead Sponsor

Trials

649

Recruited

130,000+

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Jay Backstrom

Celgene

Chief Medical Officer since 2016

MD

Mark Alles

Celgene

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Published Research Related to This Trial

In a randomized phase III trial involving 246 high-risk patients, high-dose sequential chemotherapy with autologous stem-cell transplantation (R-HDS) did not show improved 3-year event-free survival compared to standard R-CHOP treatment, with rates of 62% versus 65% respectively.

While R-HDS initially showed better disease-free survival (91% vs 79%), this advantage diminished due to late treatment-related deaths, and R-HDS was associated with significantly higher rates of hematologic toxicity and infectious complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Trial Comparing R-CHOP Versus High-Dose Sequential Chemotherapy in High-Risk Patients With Diffuse Large B-Cell Lymphomas. Cortelazzo, S., Tarella, C., Gianni, AM., et al.[2018]

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 CEOP chemotherapy regimen, which substitutes epirubicin for doxorubicin, demonstrated a high efficacy with a complete remission rate of 64.3% in 186 patients with intermediate- or high-grade non-Hodgkin lymphoma, particularly benefiting elderly patients.

Long-term follow-up showed that 79.8% of patients who achieved complete remission remained disease-free at a median of 86.9 months, indicating that CEOP is not only effective but also well-tolerated, with no deaths from cardiac toxicity reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of patients with intermediate or high-grade non-Hodgkin lymphoma treated with a combination of cyclophosphamide, epirubicin, vincristine, and prednisone. Rossini, F., Terruzzi, E., Perego, D., et al.[2015]

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]

In a study of 37 patients with relapsed/refractory aggressive lymphoma, the PACEBOM regimen demonstrated an overall response rate of 65% for Diffuse Large B-Cell Lymphoma (DLBCL), 70% for T-Cell Lymphoma (TCL), and 71% for Hodgkin lymphoma, indicating its efficacy as a treatment option.

The combination of PACEBOM with rituximab showed manageable toxicity, with the most common severe side effects being neutropenia (46%) and anemia (24%), suggesting that this treatment can be safely administered to patients previously treated with rituximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and toxicity of PACEBOM chemotherapy in relapsed/refractory aggressive lymphoma in the rituximab era. Tamjid, B., Mckendrick, J., Schwarer, A., et al.[2018]

The intensified chemotherapy regimen for children with advanced B-cell malignancies resulted in a high overall complete remission rate of 93%, with 66 out of 74 patients with B-ALL and 57 out of 59 patients with stage IV SNCCL achieving remission.

The 4-year event-free survival rates were promising, at 65% for B-ALL and 79% for stage IV SNCCL, indicating that the intensified treatment may significantly improve long-term outcomes for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved survival for children with B-cell acute lymphoblastic leukemia and stage IV small noncleaved-cell lymphoma: a pediatric oncology group study. Bowman, WP., Shuster, JJ., Cook, B., et al.[2017]

In a study of 20 patients with untreated poor prognosis diffuse large B-cell lymphoma (DLBCL), the two-weekly dose-adjusted EPOCH-like chemotherapy (DA-EDOCH14-R) showed a promising three-year progression-free survival (PFS) rate of 95%, compared to 74% in a previous trial with a three-weekly regimen.

The treatment was well-tolerated with manageable toxicity and no therapy-related deaths, highlighting its safety, especially for patients with a high-risk prognosis (age-adjusted International Prognostic Index of 3), where PFS reached 100% compared to just 30% in the previous trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-weekly dose-adjusted (DA)-EPOCH-like chemotherapy with high-dose dexamethasone plus rituximab (DA-EDOCH14-R) in poor-prognostic untreated diffuse large B-cell lymphoma. García-Suárez, J., Flores, E., Callejas, M., et al.[2015]

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 60 previously untreated patients with intermediate- or high-grade non-Hodgkin's lymphomas, the combination chemotherapy regimen CEOP-B/VIMB achieved a high complete remission rate of 77% and a 48-month overall survival rate of 70%.

The treatment demonstrated mild toxicity, making it a favorable option compared to third-generation regimens, while patient outcomes were significantly influenced by factors such as serum LDH levels and performance status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CEOP-B alternated with VIMB in intermediate-grade and high-grade non-Hodgkin's lymphoma: a pilot study. De Lena, M., Ditonno, P., Lorusso, V., et al.[2017]

In a study of 125 patients with advanced stage diffuse large cell non-Hodgkin's lymphoma, the MACOP-B chemotherapy regimen achieved a high complete response rate of 84%, indicating its efficacy in treating this aggressive cancer.

The overall toxicity of the MACOP-B treatment was manageable, with only 4.8% of patients experiencing treatment-related deaths, and the most common side effects were mucocutaneous, suggesting that while effective, there is still room for improvement in reducing toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated clinical experience with MACOP-B. Klimo, P., Connors, JM.[2017]

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 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 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]

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 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]

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