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

Trial Summary

What is the purpose of this trial?

This phase II trial tests the effectiveness of golcadomide and rituximab as bridging treatment before chimeric antigen receptor (CAR) T-cell therapy in patients with aggressive B-cell non-Hodgkin lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Patients that are able to receive CAR T-cell therapy have a potential for cure, however, many will not be qualified to receive therapy due to relapse. Bridging therapy is therapy intended to transition a patient from one therapy or medication to another or maintain their health or status until they are a candidate for a therapy or have decided on a therapy. Golcadomide may help block the formation, growth or spread of cancer cells. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Giving golcadomide and rituximab as bridging therapy before CAR T-cell therapy may kill more tumor cells and may improve the chance of proceeding to CAR T-cell therapy in patients with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma.

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.

What data supports the effectiveness of the drug combination Golcadomide and Rituximab for treating non-Hodgkin's lymphoma?

Rituximab, when added to standard chemotherapy, has been shown to improve survival in patients with non-Hodgkin's lymphoma. It has also demonstrated high response rates when used in combination with other treatments for various types of lymphoma, suggesting its potential effectiveness in combination therapies. ^{1 2 3 4 5}

Is the combination of Golcadomide and Rituximab safe for humans?

Rituximab, used in treating non-Hodgkin's lymphoma, is generally safe with mild to moderate side effects mostly related to infusion, such as reactions from cytokine release (proteins that can affect immune responses). Serious side effects like myelosuppression (reduced bone marrow activity) and infections are less common, especially when Rituximab is used alone rather than with chemotherapy. ^{6 7 8 9 10}

How does the drug Golcadomide + Rituximab differ from other treatments for non-Hodgkin's lymphoma?

Golcadomide + Rituximab is unique because it combines Rituximab, a well-established monoclonal antibody targeting B-cell lymphomas, with Golcadomide, which may offer a novel mechanism of action or enhanced efficacy. Rituximab is known for its high activity and low toxicity, and combining it with Golcadomide could potentially improve outcomes for patients who are refractory to standard treatments. ^{5 11 12 13 14}

Research Team

Grzegorz S. Nowakowski, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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, 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 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]

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, 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]

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 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]

References

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

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

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

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

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

Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma. [2021]

4. 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]

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

Evolving role of rituximab in the treatment of patients with non-Hodgkin's lymphoma. [2015]

6. 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]

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

Efficacy and safety assessment of prolonged maintenance with subcutaneous rituximab in patients with relapsed or refractory indolent non-Hodgkin lymphoma: results of the phase III MabCute study. [2022]

8. Croatia pubmed.ncbi.nlm.nih.gov

[Rituximab in the treatment of B-cell non-Hodgkin lymphoma]. [2015]

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

Single-agent monoclonal antibody efficacy in bulky non-Hodgkin's lymphoma: results of a phase II trial of rituximab. [2022]

10. United States 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. [2022]

11. Japan 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]. [2015]

12. England pubmed.ncbi.nlm.nih.gov

Rituximab: clinical development and future directions. [2019]

13. England pubmed.ncbi.nlm.nih.gov

Rituximab therapy in malignant lymphoma. [2022]

14. England pubmed.ncbi.nlm.nih.gov

Extended Rituximab (anti-CD20 monoclonal antibody) therapy for relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma. [2022]