Golcadomide + Rituximab for Follicular Lymphoma

(GOLSEEK-2 Trial)

Recruiting in Palo Alto (17 mi)

+115 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Celgene

Disqualifiers: Transformed lymphoma, Follicular large cell, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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 Follicular Lymphoma (FL).

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.

What data supports the effectiveness of the drug combination Golcadomide + Rituximab for treating follicular lymphoma?

Research shows that adding rituximab to chemotherapy significantly improves outcomes for patients with follicular lymphoma, reducing the risk of treatment failure and prolonging the time to treatment failure. Rituximab, when combined with other drugs, has shown high therapeutic efficacy in treating low-grade lymphomas. ^{1 2 3 4 5}

Is the combination of Golcadomide and Rituximab safe for treating follicular lymphoma?

Rituximab, used in treating follicular lymphoma, has been shown to be generally safe, with some patients experiencing serious side effects like myelosuppression (reduced bone marrow activity) and infections. The safety profile of Rituximab is well-established, but new side effects can still emerge, so it's important for clinicians to monitor and manage these. The combination with Golcadomide specifically hasn't been detailed in the provided research, so consulting with a healthcare provider for the latest safety data is recommended. ^{6 7 8 9 10}

What makes the drug Golcadomide + Rituximab unique for treating follicular lymphoma?

The combination of Golcadomide with Rituximab for follicular lymphoma is unique because it pairs Rituximab, a well-established monoclonal antibody, with a novel agent, Golcadomide, potentially offering a new mechanism of action or enhanced efficacy compared to existing treatments that typically combine Rituximab with chemotherapy or other biological agents. ^{1 2 7 11 12}

Eligibility Criteria

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

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

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.

Trial Timeline

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

Treatment Details

Interventions

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

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.

Participant Groups

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Local Institution - 0031 Rochester, MN

Alaska Oncology and Hematology Anchorage, AK

Local Institution - 0205 Chicoutimi, Canada

CIUSSS- saguenay-Lac-Saint-Jean Chicoutimi, Canada

More Trial Locations

Who Is Running the Clinical Trial?

Celgene Lead Sponsor

References

1. United States 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. [2022] Phase 2 studies suggest that the monoclonal antibody rituximab may improve the prognosis of patients with follicular lymphoma (FL) when it is added to chemotherapy. In the current study, 428 patients with untreated, advanced-stage FL were randomly assigned for therapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) alone (n = 205) or CHOP combined with rituximab (R-CHOP) (n = 223). R-CHOP reduced the relative risk for treatment failure by 60% and significantly prolonged the time to treatment failure (P

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

Biological therapy doublets: pairing rituximab with interferon, lenalidomide, and other biological agents in patients with follicular lymphoma. [2021] Rituximab (R) is a monoclonal antibody with high therapeutic efficacy in low-grade CD20+ lymphoma. The combination of R with chemotherapy is the most common treatment option for patients with follicular lymphoma (FL). The efficacy of R has also been shown to be augmented, when used in combinations with biologicals such as interferon-alpha-2a (IFN), bortezomib, or lenalidomide. The best combination of these drugs are not well defined and a better understanding of pharmacokinetics and timing of drugs relative to the rituximab infusion is crucial. Other new targeted agents, such as inhibitors of BTK and PI3Kdelta, have also been promising in FL. Translational research questions should be added to clinical trial protocols to increase the knowledge on how the tumor microenvironment and the host immune system affect the response to the different drugs and combinations with the aim of a more individualized therapy.

3. United States 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. [2016] Radioimmunotherapy has been approved for relapsed follicular lymphoma (FL), including rituximab-refractory FL. This study was designed to determine the CR rate with short-course chemoimmunotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (CHOP-R) followed by 90-Y ibritumomab tiuxetan (RIT) with extended rituximab as first-line treatment.

4. England pubmed.ncbi.nlm.nih.gov

Treating relapsed follicular lymphoma. [2019] Advanced follicular lymphoma (FL) remains an incurable disease, at least with conventional therapy. Despite the long remission and disease-free periods that can be currently achieved with treatment, the disease will ultimately relapse in most of the patients. Areas covered: This article reviews the current spectrum of therapies for patients with relapsed FL in the rituximab area. It will revisit current therapies, approaches to therapeutic decision making and novel agents under investigation. Expert commentary: At present, rituximab or second generation anti-CD20 antibodies either as single agent or in combination with chemotherapy, anti-CD20 maintenance therapy and stem cell transplant remain effective treatment options for relapsed patients. A plethora of new targeted agents and novel approaches such as immunotherapy are currently under investigation,thus the landscape is rapidly evolving. In this context, therapeutic decisions for individual patients in a disease which is increasingly becoming a chronic condition require a tailored approach integrating multiple clinical parameters with particular considerations of patients' preferences and quality of life.

5. England pubmed.ncbi.nlm.nih.gov

Monoclonal antibody therapy in lymphoid malignancies. [2019] The concept of targeted therapy for patients with advanced cancer has intrigued researchers for many years. The lymphoid malignancies are particularly good candidates for this therapeutic approach, due to the identification of multiple lymphocyte-specific antigens. The recent introduction of rituximab marks the beginning of a new era in the treatment of lymphoid malignancies. Rituximab is one of the most active single agents for patients with refractory indolent lymphoma, producing response rates of approximately 50%, with low toxicity and a brief duration of treatment. Additional uses of rituximab are being evaluated in ongoing clinical trials, and are briefly reviewed. As a first-line agent, responses of approximately 70% are produced in patients with indolent lymphoma, with minimal toxicity. A substantial percentage of patients can be successfully retreated with rituximab, with second remission durations longer than the first remission (14-16 months versus 12 months). Multiple combination regimens using rituximab plus chemotherapy are also being evaluated. Although the role of these combined approaches is incompletely defined, high complete response rates can be obtained, with a higher rate of molecular complete remission (i.e., eradication of detectable bcl-2 rearrangements) than has been observed in patients receiving chemotherapy alone. Rituximab is also being evaluated in other CD20(+) lymphoid malignancies including large-cell lymphoma, chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. Within the next 12 months, several additional monoclonal antibodies will be available for the treatment of lymphoid malignancies. These include the radioimmunoconjugates tositumomab (Bexxar) and ibritumomab (Zevalin), as well as Campath-1H (anti-CD52) monoclonal antibody. Early clinical data with each of these agents are also briefly reviewed.

6. New Zealand pubmed.ncbi.nlm.nih.gov

Critical appraisal of rituximab in the maintenance treatment of advanced follicular lymphoma. [2022] Rituximab is an IgG1, chimeric monoclonal antibody specifically designed to recognize the CD20 antigen expressed on the surface of normal and malignant B-lymphocytes, from the B-cell precursor to the mature B-cells of the germinal center, and by most neoplasms derived from B-cells. After 2 decades of use, rituximab is firmly positioned in the treatment of follicular lymphoma (FL), both in the front line and in the relapsing disease, improving previous results by including it in classical chemotherapy regimens. However, the pharmacology of rituximab continues to generate controversial issues especially regarding the mechanisms of action in vivo. The contribution of rituximab as a maintenance treatment in FL has been significant progress in the management of this disease without an increase in side effects or a decrease in the quality of life of patients. With the widespread use of rituximab, there are new security alerts and side effects not previously detected in the pivotal trials that clinicians should learn to recognize and manage. In this article, we will review the pharmacokinetics and pharmacodynamics of rituximab, the management issues in the treatment of advanced FL focusing on maintenance rituximab, its long-term efficacy and safety profile, and its effect on the quality of life.

7. Italy pubmed.ncbi.nlm.nih.gov

Rituximab serum concentrations during immuno-chemotherapy of follicular lymphoma correlate with patient gender, bone marrow infiltration and clinical response. [2021] Treatment of follicular lymphoma with rituximab is currently recommended at a dose of 375 mg/m(2). We aimed to provide a rationale for optimal dosing and scheduling of this anti-CD20 antibody based on pharmacokinetics.

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

Safety and efficacy of rituximab as first- and second line treatment in multiple sclerosis - A cohort study. [2022] Rituximab is increasingly used as off-label therapy in multiple sclerosis (MS). More data are needed on safety and efficacy of rituximab, particularly in cohorts of de novo patients and patients in early therapy escalation.

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

A systematic review of comparative schedule-related toxicities with maintenance rituximab in follicular and mantle cell lymphomas. [2019] Abstract We conducted a systematic review of grade 3/4 adverse events (AEs) reported in prospective trials enrolling patients with follicular lymphoma (FL) and mantle cell lymphoma (MCL) receiving maintenance rituximab (MR). Random-effects models were used to calculate summary estimates and 95% confidence intervals for the proportion of AEs occurring during MR. Differences by induction program, histology, setting and MR schedule were examined by stratified analyses and univariate random-effects meta-regression. Eleven trials met the search criteria, with nine sufficiently reporting AEs during the MR phase. Of 1009 patients receiving MR, the proportion experiencing cumulative grade 3/4 toxicity was 24% (95% confidence interval [CI]: 14-36%). Patients receiving MR every 6 months as four weekly infusions for 2 years had significantly less toxicity compared with those receiving MR every 2 months (10% vs. 28%; p = 0.035). Patients treated with rituximab alone during induction had fewer toxicities compared to those treated with rituximab plus chemotherapy induction (12% vs. 35%; p = 0.031). Myelosuppression and infections were the most common toxicities. Our literature analysis suggests that MR given every 6 months and rituximab alone as induction may be associated with fewer grade 3/4 AEs for patients with FL and MCL; however, assessing the true independent impact of induction regimens and schedule on toxicity will require prospective trials.

10. England pubmed.ncbi.nlm.nih.gov

A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma. [2021] Rituximab in combination with chemotherapy has shown efficacy in patients with diffuse large B-cell lymphoma (DLBCL) for more than 15 years. HLX01 was developed as the rituximab biosimilar following a stepwise approach to demonstrate biosimilarity in analytical, pre-clinical, and clinical investigations to reference rituximab. With demonstrated pharmacokinetic similarity, a phase 3 multi-center, randomized, parallel, double-blind study (HLX01-NHL03) was subsequently conducted to compare efficacy and safety between HLX01 plus cyclophosphamide, doxorubicin, vincristine, and prednisone (H-CHOP) and reference rituximab plus CHOP (R-CHOP) in a total of 407 treatment-naïve, CD20-positive DLBCL patients aged 18-80 years. The primary efficacy endpoint was best overall response rate (ORR) within six cycles of treatment in the per-protocol set (PPS). Secondary endpoints included 1-year efficacy outcomes, safety, and immunogenicity profile. The results showed difference in ORRs [H-CHOP 94.1%; R-CHOP 92.8%] between two treatment groups was 1.4% (95% confidence interval [CI], - 3.59 to 6.32, p = 0.608) which falls within the pre-defined equivalence margin of ± 12%. The safety profile was comparable between the treatment groups, with a similar overall incidence of treatment-emergent adverse events (H-CHOP 99.5%, R-CHOP 99.0%, p = 1.000) and serious adverse events (H-CHOP 34.0%, R-CHOP 32.5%, p = 0.752). This study established bioequivalence in efficacy and safety between HLX01 and reference rituximab. The trial was registered at http://www.chinadrugtrials.org.cn on 26 August 2015 [#CTR20150583].

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

Optimization of postremission therapy in follicular lymphoma: efficacy of rituximab maintenance. [2019] Rituximab has been proven to be an important part of the treatment of newly diagnosed and relapsed or refractory follicular lymphoma both alone and in combination with chemotherapy. Given its tolerability, rituximab has now been investigated in the maintenance setting in an effort to further improve progression-free and overall survival in patients with follicular lymphoma.

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

Rituximab plus chemotherapy in follicular and mantle cell lymphomas. [2022] Rituximab shows high single-agent activity in both previously untreated and relapsed or refractory indolent non-Hodgkin's lymphoma. In combination with chemotherapy, rituximab has achieved response rates higher than 90% with long duration of remission in phase II studies. Therefore, randomized phase III studies have been undertaken to determine whether rituximab plus chemotherapy can significantly improve outcomes compared with conventional chemotherapy in indolent non-Hodgkin's lymphoma. A study by the German Low-Grade Study Group has evaluated rituximab in combination with FCM (fludarabine/cyclophosphamide/mitoxantrone) in a randomized setting versus FCM alone in patients with relapsed or refractory follicular, mantle cell, or lymphoplasmacytic lymphoma. An interim analysis of 94 evaluable patients has shown a significantly higher response rate for rituximab plus FCM (overall response rate [ORR] 83%; complete response [CR] 35%) compared with FCM alone (ORR 58%; CR 13%), with no increase in toxicity. Superiority of rituximab plus FCM was seen in both follicular lymphoma (n = 53; ORR 92% v 75%; CR 40% v 21%) and, most strikingly, in mantle cell lymphoma (n = 38; ORR 65% v 33; CR 35% v 0%). A trend towards longer overall and disease-free survival for rituximab plus FCM has been observed, but longer follow-up is required.