Golcadomide + Rituximab for Follicular Lymphoma

(GOLSEEK-2 Trial)

Recruiting at 119 trial locations

Overseen By First line of the email MUST contain the NCT# and Site #.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Celgene

Disqualifiers: Transformed lymphoma, Follicular large cell, 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: 6 months

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the combination of golcadomide and rituximab to evaluate their effectiveness and safety for individuals with advanced-stage follicular lymphoma, a type of blood cancer. Participants will receive various treatments, such as rituximab with chemotherapy or rituximab with different doses of golcadomide, to identify the best option. The trial seeks individuals newly diagnosed with advanced-stage follicular lymphoma who have not yet received any systemic treatment. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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 study team or your doctor.

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

Research has shown that the combination of golcadomide and rituximab has been tested for safety in patients with diffuse large B-cell lymphoma (DLBCL). In these studies, the treatment was generally well-tolerated, with most patients not experiencing severe side effects. The side effects that did occur were consistent across different doses of golcadomide.

Although specific side effects were not listed, the progression of the study to its current phase suggests the treatment is reasonably safe so far. Additionally, rituximab is already an approved treatment for some types of lymphoma, providing some reassurance about its safety.

Prospective trial participants should consult a healthcare provider to understand what side effects to expect. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Golcadomide combined with Rituximab for follicular lymphoma because it offers a new approach compared to standard treatments like R-CHOP or Rituximab with Bendamustine. Golcadomide is distinctive due to its novel mechanism of action, which may enhance the immune system's ability to target cancer cells more effectively. Additionally, the combination with Rituximab, a well-established therapy, could potentially improve outcomes by attacking the lymphoma from multiple angles. This innovative approach aims to provide more effective and potentially faster results for patients with this type of lymphoma.

What evidence suggests that this trial's treatments could be effective for Follicular Lymphoma?

Research has shown that combining golcadomide and rituximab, which participants in this trial may receive, could be a promising treatment for follicular lymphoma. In patients whose follicular lymphoma returned or did not respond to other treatments, this combination proved effective for a longer duration. It was also well tolerated, with patients experiencing no severe side effects. Additionally, participants in this trial may receive golcadomide with R-CHOP, which demonstrated strong cancer-fighting effects in aggressive B-cell lymphoma, suggesting potential effectiveness for other lymphoma types as well. Overall, these findings suggest that golcadomide plus rituximab could be an effective treatment option for follicular lymphoma. ^{1 2 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 newly diagnosed advanced stage Follicular Lymphoma (grades 1, 2, or 3a) who haven't had systemic treatment. They can have had radiation or surgery if it was for stage I disease. Participants must show symptoms like large masses, fever, night sweats, weight loss over 10%, low blood counts due to lymphoma, or organ compression.

Inclusion Criteria

I have experienced fever, night sweats, or significant weight loss without a clear reason.

I have not had any drug treatments for my follicular lymphoma, but I may have had radiation or surgery if it was stage I.

My spleen is enlarged and extends below my belly button.

Exclusion Criteria

My lymphoma is classified as Follicular Large Cell or Grade 3b.

Other protocol-defined Inclusion/Exclusion criteria apply

My lymphoma has changed into a more aggressive form.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Golcadomide in combination with Rituximab or Rituximab with Chemotherapy

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Long-term Follow-up

Participants are monitored for progression-free survival and overall survival

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

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

Trial Overview The study tests the effectiveness and safety of a new drug combo: Golcadomide with Rituximab versus standard treatments (Prednisone, Vincristine, Bendamustine, Doxorubicin & Cyclophosphamide). It aims to see how well this new mix works in treating Follicular Lymphoma compared to existing therapies.

How Is the Trial Designed?

Group I: Rituximab + Chemotherapy Experimental Treatment 6 Interventions

R-CHOP (Rituximab, Doxorubicin, Vincristine, Cyclophosphamide, Prednisone) or Rituximab + Bendamustine

Group II: Golcadomide Dose 2 + Rituximab Experimental Treatment 2 Interventions

Group III: Golcadomide Dose 1 + Rituximab Experimental Treatment 2 Interventions

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 phase II trial involving 29 patients with untreated follicular lymphoma, rituximab combined with fludarabine and mitoxantrone achieved a high overall response rate of 100% and a complete remission rate of 66%, with notably higher remission rates in female patients.

Pharmacokinetic analysis revealed significant variability in rituximab serum concentrations, which correlated with treatment outcomes; specifically, higher serum levels were linked to better remission quality and longer progression-free survival, suggesting that dosing may need to be tailored based on patient characteristics like gender and bone marrow infiltration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab serum concentrations during immuno-chemotherapy of follicular lymphoma correlate with patient gender, bone marrow infiltration and clinical response. Jäger, U., Fridrik, M., Zeitlinger, M., et al.[2021]

In a systematic review of 11 trials involving 1009 patients with follicular lymphoma and mantle cell lymphoma, 24% experienced grade 3/4 adverse events during maintenance rituximab treatment, indicating a notable risk of severe toxicity.

Patients receiving maintenance rituximab every 6 months had significantly lower toxicity rates (10%) compared to those treated every 2 months (28%), and those who received rituximab alone during induction had fewer adverse events than those who received it with chemotherapy (12% vs. 35%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of comparative schedule-related toxicities with maintenance rituximab in follicular and mantle cell lymphomas. Nabhan, C., Ollberding, NJ., Villines, D., et al.[2019]

Rituximab is effective in treating both newly diagnosed and relapsed or refractory follicular lymphoma, whether used alone or with chemotherapy.

Due to its good tolerability, rituximab is being explored for maintenance therapy to enhance progression-free and overall survival in patients with follicular lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimization of postremission therapy in follicular lymphoma: efficacy of rituximab maintenance. Roy, R., Gordon, LI.[2019]

Rituximab is highly effective for treating low-grade CD20+ lymphoma, especially when combined with chemotherapy, which is the standard treatment for follicular lymphoma (FL).

The efficacy of rituximab can be enhanced by combining it with biological agents like interferon-alpha-2a, bortezomib, or lenalidomide, but more research is needed to determine the best combinations and timing of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological therapy doublets: pairing rituximab with interferon, lenalidomide, and other biological agents in patients with follicular lymphoma. Kimby, E.[2021]

In a study of 428 patients with untreated advanced-stage follicular lymphoma, adding rituximab to the standard CHOP chemotherapy significantly reduced the risk of treatment failure by 60% and improved overall survival rates.

While the combination therapy (R-CHOP) led to a higher incidence of myelosuppression, severe infections remained rare, indicating that rituximab can enhance treatment efficacy without causing major safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Hiddemann, W., Kneba, M., Dreyling, M., et al.[2022]

A phase 3 study involving 407 treatment-naïve patients with diffuse large B-cell lymphoma demonstrated that HLX01, a biosimilar to rituximab, has comparable efficacy to the reference drug, with overall response rates of 94.1% for HLX01 and 92.8% for rituximab, falling within the pre-defined equivalence margin.

The safety profiles of HLX01 and rituximab were similar, with nearly identical rates of treatment-emergent adverse events (99.5% vs. 99.0%) and serious adverse events (34.0% vs. 32.5%), confirming that HLX01 is a safe alternative to rituximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma. Shi, Y., Song, Y., Qin, Y., et al.[2021]

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]

Rituximab is an effective treatment for follicular lymphoma (FL), improving outcomes when used in combination with traditional chemotherapy, and has shown significant benefits as a maintenance therapy without increasing side effects or compromising patients' quality of life.

Despite its long history of use, new safety alerts and side effects have emerged that clinicians need to be aware of, highlighting the importance of ongoing monitoring and management in patients receiving rituximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical appraisal of rituximab in the maintenance treatment of advanced follicular lymphoma. Aguiar-Bujanda, D., Blanco-Sánchez, MJ., Hernández-Sosa, M., et al.[2022]

Rituximab has shown a response rate of approximately 70% as a first-line treatment for indolent lymphoma, with low toxicity and the ability to retreat patients successfully, leading to longer remission durations.

Combination therapies using rituximab with chemotherapy have resulted in high complete response rates and a greater likelihood of molecular complete remission compared to chemotherapy alone, indicating its potential to enhance treatment outcomes in lymphoid malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal antibody therapy in lymphoid malignancies. Hainsworth, JD.[2019]

In a study of 60 patients with symptomatic or bulky follicular lymphoma, a combination of short-course chemoimmunotherapy (CHOP-R) followed by radioimmunotherapy (RIT) led to a significant increase in complete response (CR) rates, from 40% after CHOP-R to 82% after RIT, as assessed by imaging.

The study found that patients who did not achieve a complete metabolic response on PET imaging after CHOP-R had a higher risk of relapse, highlighting the importance of early PET assessment in predicting treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of short-course CHOP-R followed by 90Y-ibritumomab tiuxetan and extended rituximab in previously untreated follicular lymphoma. Jacobs, SA., Swerdlow, SH., Kant, J., et al.[2016]

Rituximab and second-generation anti-CD20 antibodies, either alone or combined with chemotherapy, remain effective treatment options for patients with relapsed follicular lymphoma, highlighting their role in managing this incurable disease.

The treatment landscape for relapsed follicular lymphoma is evolving with new targeted agents and immunotherapies under investigation, emphasizing the need for personalized treatment plans that consider individual patient factors and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating relapsed follicular lymphoma. Erblich, T., Montoto, S.[2019]

In a study of 365 multiple sclerosis patients treated with rituximab over four years, the treatment showed a very low annualized relapse rate (ARR) of 0.03, indicating high efficacy in preventing disease relapses.

While rituximab was generally safe, with 79% of patients achieving no evidence of disease activity (NEDA-3), there were notable risks of infections and neutropenia, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of rituximab as first- and second line treatment in multiple sclerosis - A cohort study. Torgauten, HM., Myhr, KM., Wergeland, S., et al.[2022]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3018/533620/Golcadomide-GOLCA-Rituximab-RTX-Demonstrates

Golcadomide (GOLCA) ± Rituximab (RTX) Demonstrates ... Golcadomide (GOLCA) ± Rituximab (RTX) demonstrates durable efficacy and is well tolerated in patients (pts) with relapsed/refractory follicular lymphoma (R/R ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06425302

NCT06425302 | A Study to Evaluate the Efficacy and ... The purpose of this study is to assess the efficacy and safety of golcadomide in combination with rituximab in participants with newly diagnosed advanced stage ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124091390

Golseek-2: A Phase 2 Randomized, Open-Label Study to ... A randomized phase 2 trial assessing the efficacy and safety of GOLCA-R as a chemo-free option in pts with newly diagnosed advanced-stage FL.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12081106/

Follicular lymphoma: contemporary clinical management with ... In the pre-rituximab era, long-term follow-up data from the Dana-Farber Cancer Institute showed an 8-year disease-free survival rate of 42% and an OS rate of 66 ...

5. onclive.com onclive.com/view/frontline-golcadomide-r-chop-combo-elicits-antitumor-activity-in-aggressive-b-cell-lymphoma

Frontline Golcadomide/R-CHOP Combo Elicits Antitumor ... Golcadomide given at 0.4 mg plus R-CHOP elicited a high rate of metabolic responses in patients with previously untreated aggressive B-cell lymphoma.

6. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/4496/501000/Efficacy-and-Safety-of-Golcadomide-a-Novel

Efficacy and Safety of Golcadomide, a Novel Cereblon E3 ... Conclusions: Golcadomide oral therapy combined with rituximab showed promising efficacy in heavily pretreated patients with R/R DLBCL, including ...

7. bmsclinicaltrials.com bmsclinicaltrials.com/golcainnhl/golseek-2

Golseek-2 Clinical Trial Information | Bristol Myers Squibb GOLSEEK 2 is an open label randomized Phase 2 study designed to assess the efficacy and safety of golcadomide in combination with rituximab.

8. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper203131.html

Golcadomide (GOLCA) ± Rituximab ... In the GOLCA + RTX-treated safety population (n = 43), the incidence of treatment emergent adverse events (TEAEs) was similar across 0.2 and 0.4 mg dose levels ...