Golcadomide + Rituximab for Non-Hodgkin's Lymphoma

Recruiting at 6 trial locations

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: CYP3A4/5 inhibitors

Disqualifiers: Pregnancy, HIV, Hepatitis B/C, 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: 4

41 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining golcadomide, a new potential drug, with rituximab effectively treats aggressive B-cell non-Hodgkin lymphoma, a cancer affecting the immune system. It targets patients whose cancer has returned after treatment or didn't respond to previous treatments, serving as a bridge to prepare them for CAR T-cell therapy, a potential cure for some. Individuals with this type of lymphoma, who have tried one or two standard treatments without success, and who might be eligible for CAR T-cell therapy, could be a good fit for this trial. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take strong or moderate CYP3A4/5 inhibitors and inducers within 14 days before starting the study treatment. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that golcadomide and rituximab are likely to be safe?

Studies have shown that using golcadomide with rituximab is generally safe for patients. Research indicates that this combination has a safety profile similar to golcadomide alone. In trials with patients who had already tried many other treatments, this combination was well-tolerated.

Patients experienced no unexpected side effects; instead, the side effects resembled those typically seen with these medications. This suggests that the treatment is relatively safe for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Golcadomide and Rituximab for treating Non-Hodgkin's Lymphoma because it offers a novel approach to tackling this cancer. Unlike standard treatments that often rely solely on chemotherapy or monoclonal antibodies, Golcadomide introduces a new active ingredient that may enhance the effectiveness of Rituximab. Golcadomide is taken orally, which can be more convenient compared to traditional intravenous chemotherapy, and it works by potentially modulating the immune response to better target cancer cells. This combination not only aims to improve outcomes but also allows patients eligible for CAR-T therapy to integrate this advanced treatment seamlessly.

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

Research has shown that combining golcadomide with rituximab is effective for patients with relapsed or hard-to-treat diffuse large B-cell lymphoma (DLBCL). One study found that 92% of patients responded positively to this treatment, with some experiencing this effect for an average of 22 months. Furthermore, 93% of patients achieved minimal residual disease negativity, showing no signs of cancer after treatment. In this trial, participants will receive golcadomide and rituximab, which may effectively target cancer cells and potentially enable patients to proceed to CAR T-cell therapy. ^{1 2 3 5 6}

Who Is on the Research Team?

Grzegorz S. Nowakowski, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for patients with aggressive B-cell non-Hodgkin lymphoma that has either returned after treatment or hasn't responded to previous treatments. It's a bridge to CAR T-cell therapy, which may not be immediately available due to relapse. Key eligibility details are not provided.

Inclusion Criteria

Absolute neutrophil count (ANC) ≥ 1000/mcL

My doctor thinks I might be a good candidate for CAR-T therapy.

I agree not to donate blood while on golcadomide.

Exclusion Criteria

Pregnant persons

Persons of childbearing potential unwilling to employ adequate contraception

Receiving other investigational agents for lymphoma

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Bridging Treatment

Participants receive golcadomide and rituximab as bridging therapy before CAR T-cell therapy. Golcadomide is taken orally once daily on days 1-14, and rituximab is administered intravenously on days 1, 8, 15, and 22 of cycle 1, then on day 1 of subsequent cycles. Cycles repeat every 28 days for up to 2 cycles.

8 weeks

4 visits (in-person) per cycle

CAR-T Preparation

Eligible patients undergo leukapheresis and may receive 1-2 additional cycles of golcadomide and rituximab prior to undergoing standard of care CAR-T therapy.

4-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment. CAR-T ineligible patients are followed up every 3 months until progression or subsequent treatment, then every 6 months for up to 2 years. CAR-T eligible patients are followed up at 180 days after CAR-T then every 6 months for up to 2 years.

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Golcadomide
• Rituximab

Trial Overview The effectiveness of golcadomide and rituximab as bridging treatments before CAR T-cell therapy is being tested. Golcadomide might prevent cancer growth, while rituximab targets certain immune cells potentially helping kill cancer cells.

How Is the Trial Designed?

Group I: Treatment (golcadomide, rituximab) Experimental Treatment 9 Interventions

Patients receive golcadomide PO QD on days 1-14 of each cycle and rituximab IV on days 1, 8, 15 and 22 of cycle 1 and then on day 1 of all subsequent cycles. Cycles repeat every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. ELIGIBLE FOR CAR-T: After 2 cycles, patients undergo leukapheresis and may receive 1-2 additional cycles of golcadomide and rituximab prior to undergoing standard of care CAR-T therapy. INELIGIBLE FOR CAR-T: After 2 cycles, patients receive golcadomide PO QD on days 1-14 of each cycle and rituximab IV on day 1 of each cycle. Cycles repeat every 28 days for up to 10 additional cycles of golcadomide (cycles 3-12) and up to 3 additional cycles of rituximab (cycles 3-5) in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and PET/CT or CT throughout the study. Additionally, patients may undergo bone marrow aspiration and biopsy as clinically indicated.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

In a phase II study involving 37 patients with relapsed or refractory low-grade or follicular B-cell non-Hodgkin's lymphoma, Rituximab was found to be well tolerated, with most adverse events being mild and decreasing with subsequent infusions.

The treatment resulted in a 57% overall response rate, with 14% achieving a complete response and 43% a partial response, indicating significant clinical activity and suggesting that extended Rituximab treatment may be effective for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended Rituximab (anti-CD20 monoclonal antibody) therapy for relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma. Piro, LD., White, CA., Grillo-López, AJ., et al.[2022]

Rituximab, an anti-CD20 monoclonal antibody, demonstrated a 43% overall response rate in a phase II trial involving 31 patients with bulky relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma, indicating its efficacy as a treatment option.

The treatment was well-tolerated, with no patients discontinuing due to adverse events, and it showed a median time to progression of 8.1 months, highlighting its safety and potential for managing this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-agent monoclonal antibody efficacy in bulky non-Hodgkin's lymphoma: results of a phase II trial of rituximab. Davis, TA., White, CA., Grillo-López, AJ., et al.[2022]

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, an anti-CD20 monoclonal antibody, shows high efficacy in treating low-grade lymphoma, with response rates of 50-60% in relapsed cases and 60-75% as a first-line treatment, and even higher rates (85-95%) when combined with chemotherapy.

The mechanism of action for rituximab includes complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity, and its dosing may be optimized by monitoring serum levels to account for individual patient variability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of low-grade B-cell lymphoma with the monoclonal antibody rituximab. Dillman, RO.[2019]

In a study involving 1030 patients with previously untreated follicular lymphoma, the combination of rituximab and lenalidomide showed similar efficacy to rituximab plus chemotherapy, with complete response rates of 48% and 53% respectively at 120 weeks.

The safety profiles differed between the two treatments, with rituximab-chemotherapy leading to higher rates of severe neutropenia, while rituximab-lenalidomide was associated with more severe skin reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma. Morschhauser, F., Fowler, NH., Feugier, P., et al.[2021]

Rituximab, when added to standard chemotherapy, significantly improved survival rates in patients with non-Hodgkin's lymphoma.

In patients with chronic B-cell lymphocytic leukemia, the addition of rituximab to fludarabine-based regimens enhanced both response rates and overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of the safety and feasibility of rapid infusion of rituximab. Atmar, J.[2022]

The CHOEA-7 chemotherapy regimen, which includes cyclophosphamide, doxorubicin, vincristine, etoposide, and ara-C, has shown excellent results in treating patients with CD 20-positive non-Hodgkin's lymphoma.

Adding rituximab to the CHOEA-7 regimen (RCHOEA-7) further enhances treatment efficacy, indicating a promising approach for improving outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Results of dose-intense, dose-impact weekly combination chemotherapy with rituximab for patients with CD 20-positive B-cell non-Hodgkin's lymphoma]. Uzuka, Y., Saitou, Y., Saitou, K., et al.[2015]

Rituximab is a highly effective monoclonal antibody for treating various B-cell lymphomas, including follicular lymphoma and diffuse large B-cell lymphoma, demonstrating a strong activity with low toxicity.

The combination of rituximab with chemotherapy (R-CHOP) has shown the highest efficacy reported for any chemotherapy regimen in treating diffuse large B-cell lymphoma and follicular lymphoma, although some patients may still be resistant to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab therapy in malignant lymphoma. Coiffier, B.[2022]

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]

Rituximab is the first monoclonal antibody approved for treating B-cell lymphomas, showing significant effectiveness in conditions like follicular lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma.

The combination of rituximab with standard chemotherapy agents (cyclophosphamide, doxorubicin, vincristine, and prednisone) has achieved the highest efficacy reported for treating diffuse large B-cell lymphoma and follicular lymphoma, while maintaining low toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolving role of rituximab in the treatment of patients with non-Hodgkin's lymphoma. Traullé, C., Coiffier, BB.[2015]

In a study of 40 patients with low-grade or follicular B-cell non-Hodgkin's lymphoma, the combination of Rituxan (Rituximab) and CHOP chemotherapy resulted in a high overall response rate of 95%, with 55% achieving complete remission.

The combination therapy showed promising safety, with common side effects being manageable, and it also indicated potential for clearing minimal residual disease, as evidenced by the conversion of the bcl-2 translocation from positive to negative in several patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. Czuczman, MS., Grillo-López, AJ., White, CA., et al.[2022]

Rituximab, a chimeric anti-CD20 monoclonal antibody, has shown to induce responses in nearly 50% of patients with relapsed follicular/low-grade non-Hodgkin's lymphoma, with complete remissions occurring in 6% of cases, highlighting its efficacy in treating this type of cancer.

The drug is generally well tolerated, with common side effects being mild to moderate fevers and chills, and it is also effective against various other B-cell malignancies, suggesting its potential for broader applications in both cancer treatment and autoimmune disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab: clinical development and future directions. Cheson, BD.[2019]

Citations

1. 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 ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0006497123110974

Efficacy and Safety of Golcadomide, a Novel Cereblon E3 ... We report efficacy and safety results for golcadomide + rituximab in patients with DLBCL treated in Part B expansion on a 14 days on/14 days off schedule.

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

Golcadomide (GOLCA) ± Rituximab ... Responses were durable, with median DOR of 22 mo (range, 2–51) at a median follow up of 30 mo. 33% of pts (4/12) have completed 2 yrs of protocol defined GOLCA ...

4. news.bms.com news.bms.com/news/details/2023/Two-Early-Studies-Evaluating-Potential-First-in-Class-CELMoD-Agent-Golcadomide-for-the-Treatment-of-Non-Hodgkin-Lymphomas-Presented-at-ASH-2023/default.aspx

Two Early Studies Evaluating Potential First-in-Class ... Minimal residual disease negativity at the end of treatment was achieved in 93% (14/15) of patients treated with 0.4 mg of golcadomide plus R- ...

5. clinicaloptions.com clinicaloptions.com/activities/oncology/latest-data-on-celmods-in-nhl/80596/content

Latest Data on CELMoDs in NHL In the 25 patients treated with 0.4 mg golcadomide plus rituximab, the ORR was 92%, while in the 22 patients treated with 0.2 mg golcadomide ...

6. 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 ...