Golcadomide + R-CHOP for B-Cell Lymphoma

(GOLSEEK-1 Trial)

Recruiting at 583 trial locations

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

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Celgene

Disqualifiers: Other lymphoma subtypes, CNS involvement, others

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

The purpose of this study is to compare the effectiveness and safety of golcadomide in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy vs placebo in combination with R-CHOP chemotherapy in participants with previously untreated high-risk large B-cell lymphoma (LBCL).

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.

What data supports the effectiveness of the drug Golcadomide + R-CHOP for B-Cell Lymphoma?

Research shows that adding rituximab to CHOP chemotherapy improves outcomes for aggressive B-cell lymphoma. Additionally, similar regimens like PACEBOM and CODOX-M/IVAC, which include components of R-CHOP, have shown effectiveness in treating various types of lymphoma. ^{1 2 3 4 5}

What safety data exists for the Golcadomide + R-CHOP treatment for B-Cell Lymphoma?

The R-CHOP regimen, which includes drugs like cyclophosphamide, doxorubicin, vincristine, and prednisone, is known to have manageable toxicity, but doxorubicin can cause heart-related side effects, especially in older patients. Studies have shown that while the treatment is generally safe, there is a risk of heart problems, and some regimens have substituted doxorubicin with other drugs to reduce this risk. ^{6 7 8 9 10}

What makes the drug Golcadomide + R-CHOP unique for treating B-cell lymphoma?

The addition of Golcadomide to the standard R-CHOP regimen for B-cell lymphoma is unique because it introduces a new component that may enhance the effectiveness of the existing treatment. R-CHOP is already a well-established therapy for this type of cancer, and Golcadomide could potentially offer additional benefits, although specific details about its mechanism or advantages are not provided in the available research. ^{11 12 13 14 15}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Cyclophosphamide (Alkylating agents)
• Doxorubicin (Anti-tumor antibiotic)
• Golcadomide (Other)
• Prednisone (Corticosteroid)
• Rituximab (Monoclonal Antibodies)
• Vincristine (Vinca alkaloids)

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.

Participant Groups

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 Canada, Japan for the following indications:

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

Findings from Research

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]

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 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 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]

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 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]

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]

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]

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]

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. Australia pubmed.ncbi.nlm.nih.gov

Efficacy and toxicity of PACEBOM chemotherapy in relapsed/refractory aggressive lymphoma in the rituximab era. [2018]

2. United States 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. [2017]

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

AMOPLACE treatment of intermediate-grade and high-grade malignant lymphoma: a Cancer and Leukemia Group B study. [2017]

4. 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]

5. Italy pubmed.ncbi.nlm.nih.gov

Clinical experience with biweekly CHOP plus rituximab chemoimmunotherapy for the treatment of aggressive B-cell non-Hodgkin lymphoma. [2021]

6. England 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. [2015]

7. United States 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. [2015]

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

Incidence and risk-factors of CHOP/R-CHOP-related cardiotoxicity in patients with aggressive non-Hodgkin's lymphoma. [2022]

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

Updated clinical experience with MACOP-B. [2017]

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

CEOP-B alternated with VIMB in intermediate-grade and high-grade non-Hodgkin's lymphoma: a pilot study. [2017]

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

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

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

Role of radiotherapy to bulky disease in elderly patients with aggressive B-cell lymphoma. [2022]

13. United States 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. [2018]

14. England 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. [2020]

15. 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]