EO2463 Combination Therapy for Non-Hodgkin's Lymphoma

(SIDNEY Trial)

Recruiting at 11 trial locations

Overseen By Karlijn Kroon, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Enterome

Must not be taking: Immunotherapy, Radionuclide therapy

Disqualifiers: Autoimmune disorder, CNS metastasis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken certain treatments like dexamethasone above a specific dose or immunotherapy within a certain time before starting the trial. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug EO2463 Combination Therapy for Non-Hodgkin's Lymphoma?

The drug rituximab, part of the EO2463 Combination Therapy, has shown effectiveness in treating non-Hodgkin's lymphoma, especially when used with chemotherapy. It is a monoclonal antibody that targets specific molecules on lymphoma cells, and has become a standard treatment for both indolent and aggressive forms of the disease. ^{1 2 3 4 5}

Is EO2463 combination therapy for Non-Hodgkin's Lymphoma safe?

The combination of vorinostat and rituximab, which includes rituximab (a component of EO2463 therapy), was generally well tolerated in patients with indolent B-cell non-Hodgkin lymphoma, with common side effects being manageable. Another study on a similar anti-CD20 monoclonal antibody (like rituximab) showed it was well tolerated, with no severe adverse events reported. ^{6 7 8 9 10}

How is the drug EO2463 different from other treatments for non-Hodgkin's lymphoma?

EO2463 is unique because it is being studied as a combination therapy specifically for non-Hodgkin's lymphoma, potentially offering a new approach compared to existing treatments like monoclonal antibodies and chemotherapy regimens. While other treatments focus on targeting specific molecules or using established chemotherapy drugs, EO2463 may involve novel mechanisms or combinations that are not yet standard in current therapies. ^{1 5 11 12 13}

What is the purpose of this trial?

The purpose of this study is to define the recommended Phase 2 Dose, safety, tolerability, immunogenicity, and preliminary efficacy of EO2463 during monotherapy and in combination with lenalidomide and/or rituximab in patients with indolent NHL

Research Team

Jan Fagerberg, MD

Principal Investigator

Enterome

Eligibility Criteria

Adults over 18 with certain types of indolent Non-Hodgkin Lymphoma (NHL) such as Follicular Lymphoma or Marginal Zone Lymphoma. Participants must have measurable disease, be HLA-A2 positive, and can include both newly diagnosed and those who've relapsed after treatment. Excludes pregnant women, individuals on high-dose steroids, those with aggressive lymphoma subtypes or other recent cancers, uncontrolled brain metastasis, autoimmune disorders, organ transplants, HIV/HBV/HCV infections.

Inclusion Criteria

Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.

I am HLA-A2 positive.

I am a male or a female not pregnant or breastfeeding.

Exclusion Criteria

I have previously been treated with EO2463.

I have or might have an autoimmune disorder, including conditions like Guillain-Barré syndrome.

I do not have uncontrolled brain metastasis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

EO2463 monotherapy for 6 weeks, followed by combination with lenalidomide and/or rituximab

24 months

Weekly visits during initial treatment phase

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 7 years

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• EO2463
• Lenalidomide
• Rituximab

Trial Overview The trial is testing EO2463 alone and in combination with lenalidomide and/or rituximab to determine the optimal dose for Phase 2 trials. It aims to assess safety, tolerability, immune response generation (immunogenicity), and initial effectiveness against indolent NHL.

Participant Groups

Group I: Cohort 4 Experimental Treatment 3 Interventions

15 Previously treated patients with FL Or MZL. Evaluation of EO2463 at the established dose in Cohort 1 in combination with lenalidomide and with addition of rituximab from week 19 onwards (depending on response)

Group II: Cohort 3 Experimental Treatment 2 Interventions

15 Previously untreated patients with FL or MZL. Evaluation of EO2463 at the established dose in cohort 1 as monotherapy for 6 weeks and in combination with rituximab from week 7

Group III: Cohort 2 Experimental Treatment 1 Intervention

15 Previously untreated patients with FL Or MZL. Evaluation of EO2463 monotherapy at the established dose in Cohort 1

Group IV: Cohort 1 Experimental Treatment 3 Interventions

Safety Lead-In, Dose-Finding, Cohort, with a 3-by-3 design of EO2463 for 6 weeks followed by addition of lenalidomide week 7 and rituximab week 19 (depending on response). Four to 18 evaluable (previously treated) patients with Follicular Lymphoma (FL) or Marginal Zone Lymphoma (MZL) will be Included based on safety findings

Who Is Running the Clinical Trial?

Enterome

Lead Sponsor

Trials

9

Recruited

550+

Findings from Research

In a study of 18 patients with advanced aggressive non-Hodgkin's lymphoma, a combination treatment of mitoxantrone, etoposide, cisplatin, and prednisolone resulted in a 61% overall response rate, with four complete and seven partial responses.

The treatment was generally well-tolerated despite myelosuppression being the main side effect, and responders had a median survival time of 52 weeks compared to 24 weeks for nonresponders, suggesting the regimen's potential effectiveness in relapsed or resistant cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage chemotherapy for non-Hodgkin's lymphoma with a combination of mitoxantrone, etoposide, cisplatin, and prednisolone. Ohnoshi, T., Hayashi, K., Ueoka, H., et al.[2013]

Intensifying drug regimens for intermediate- and high-grade non-Hodgkin's lymphomas has successfully improved cure rates, especially with the use of growth factors and stem cell transfusions to manage side effects.

In low-grade lymphomas, while intensive therapy is more controversial, promising results show that durable remissions can be achieved in advanced-stage patients through low-dose radiation or autologous transplantation, particularly in those with good prognostic factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of non-Hodgkin's lymphoma. Portlock, CS.[2019]

The introduction of new combination chemotherapy regimens in the 1970s significantly improved treatment outcomes for patients with aggressive non-Hodgkin's lymphoma (NHL).

Recent controlled studies have shown that newer, more intensive treatment regimens have not consistently led to better results, raising questions about the effectiveness of these advancements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of aggressive non-Hodgkin's lymphoma in adults--are we doing any better? Hagberg, H., Kimby, E.[2020]

Recent phase III trials indicate that using second- and third-generation treatment regimens does not improve outcomes for patients with aggressive lymphomas, highlighting the need for new strategies.

Preliminary results suggest that while standard therapies with growth factor support show minimal benefits, high-risk patients achieving complete remission may benefit from consolidative bone marrow transplantation, and novel high-dose regimens could offer promising alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of aggressive histology lymphoma. Bartlett, NL.[2019]

Rituximab, an anti-CD20 monoclonal antibody, is now a standard treatment for non-Hodgkin's lymphoma, effective both as a standalone therapy for indolent lymphoma and in combination with chemotherapy for aggressive lymphoma.

New monoclonal antibodies targeting various molecules on lymphoma cells are in clinical development, showing potential for enhanced efficacy, especially when combined with existing therapies or when radioconjugated with anti-CD20 antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody therapy for non-Hodgkin's lymphoma. Ansell, SM.[2015]

In a study of 115 patients with Waldeyer's ring diffuse large B-cell lymphoma, those treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab (DA-EPOCH-R) showed significantly better progression-free survival (PFS) and overall survival (OS) compared to those receiving standard R-CHOP treatment, with 2-year PFS rates of 90.1% versus 80.5%.

The DA-EPOCH-R treatment was associated with fewer deaths (2 out of 42 patients) compared to R-CHOP (9 out of 42 patients) during a median follow-up of 45 months, while both treatments had similar clinical responses and treatment-related toxicities, indicating that DA-EPOCH-R is a safer and more effective option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-adjusted EPOCH-R vs. R-CHOP in frontline management of Waldeyer's ring diffuse large B-cell lymphoma: a retrospective study from a single institution. Liang, Y., Liu, X., Yang, J., et al.[2023]

The MEB chemotherapy regimen (mitoxantrone, etoposide, and bleomycin) showed promising antitumor activity in patients with non-Hodgkin's lymphoma, achieving major responses in 50% of the 22 treated patients, including 23% complete responses.

Despite a significant incidence of grade 3-4 neutropenia in 59% of patients, the toxicity profile was considered manageable, indicating that MEB could be a viable treatment option for patients who are not eligible for standard chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitoxantrone, Etoposide and bleomycin (meb) chemotherapy in non-hodgkins-lymphoma patients non-elegible for standard cyclophosphamide, Doxorubicin, vincristine and prednisone (chop) combination. Tagliaferri, P., Matano, E., Rea, A., et al.[2019]

The combination of vorinostat and rituximab showed a 46% overall response rate in 28 patients with indolent B-cell non-Hodgkin lymphoma, with a higher response of 67% in previously untreated patients, indicating its efficacy as a treatment option.

The regimen was well tolerated over a median follow-up of 25.6 months, with the most common serious side effects being manageable, suggesting a favorable safety profile for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of vorinostat and rituximab for treatment of newly diagnosed and relapsed/refractory indolent non-Hodgkin lymphoma. Chen, R., Frankel, P., Popplewell, L., et al.[2018]

In a study involving 20 patients with untreated advanced non-Hodgkin's lymphoma, the MECHOP-BM regimen resulted in a 78% overall response rate, with 33% achieving a complete response (CR).

The most significant side effect observed was leukopenia, with a mean white blood cell count dropping to 1,300/microliters, indicating that while MECHOP-BM is effective, it can lead to serious reductions in immune function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[MECHOP-BM chemotherapy in the treatment of non Hodgkin's lymphoma]. Inoue, N., Miyazaki, E., Okada, M., et al.[2006]

The chimeric anti-CD20 monoclonal antibody IBI301 was well tolerated in nine Chinese patients with CD20(+) B-cell non-Hodgkin's lymphoma, with no severe adverse events or dose-limiting toxicities reported during the study.

IBI301 effectively eliminated peripheral CD20-expressing B cells in all patients, indicating its potential efficacy in targeting B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Tolerance and pharmacodynamics phase Ⅰ clinical trial study of chimeric anti-CD20 monoclonal antibody IBI301 in Chinese patients with CD20-positive non-Hodgkin's lymphoma]. Jiang, B., Qi, JY., Sun, MY., et al.[2020]

Oral etoposide is an effective treatment for patients with previously treated lymphomas, showing clear benefits and good tolerability, especially in elderly or medically unfit patients.

The optimal dosing schedule for oral etoposide appears to be low daily doses of 50 to 100 mg for 10 to 14 days, but further studies are needed to determine its effectiveness in combination with other chemotherapy agents in previously untreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral etoposide in lymphoma. Greco, FA.[2018]

The ESHAP chemotherapy regimen showed a 53.1% overall response rate in 32 Chinese patients with refractory non-Hodgkin's lymphoma, with 31.3% achieving complete remission lasting an average of 12.2 months.

While ESHAP was effective, it had significant side effects, including severe myelosuppression and infections, and most patients relapsed within 2 years, indicating limited long-term benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ESHAP as salvage therapy for refractory non-Hodgkin's lymphoma: Taiwan experience. Wang, WS., Chiou, TJ., Liu, JH., et al.[2019]

In a study of 28 patients with recurrent or refractory lymphoma treated with the E-SHAP regimen, no objective responses were observed, indicating limited efficacy of this treatment in this patient population.

The treatment was associated with significant toxicity, particularly myelosuppression, leading to over half of the patients requiring hospitalization for neutropenia-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

E-SHAP: inadequate treatment for poor-prognosis recurrent lymphoma. Johnson, PW., Sweetenham, JW., McCallum, P., et al.[2020]

References

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

Salvage chemotherapy for non-Hodgkin's lymphoma with a combination of mitoxantrone, etoposide, cisplatin, and prednisolone. [2013]

2. Germany pubmed.ncbi.nlm.nih.gov

Management of non-Hodgkin's lymphoma. [2019]

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

Treatment of aggressive non-Hodgkin's lymphoma in adults--are we doing any better? [2020]

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

Treatment of aggressive histology lymphoma. [2019]

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

Antibody therapy for non-Hodgkin's lymphoma. [2015]

6. China pubmed.ncbi.nlm.nih.gov

Dose-adjusted EPOCH-R vs. R-CHOP in frontline management of Waldeyer's ring diffuse large B-cell lymphoma: a retrospective study from a single institution. [2023]

7. Greece pubmed.ncbi.nlm.nih.gov

Mitoxantrone, Etoposide and bleomycin (meb) chemotherapy in non-hodgkins-lymphoma patients non-elegible for standard cyclophosphamide, Doxorubicin, vincristine and prednisone (chop) combination. [2019]

8. Italy pubmed.ncbi.nlm.nih.gov

A phase II study of vorinostat and rituximab for treatment of newly diagnosed and relapsed/refractory indolent non-Hodgkin lymphoma. [2018]

9. Japan pubmed.ncbi.nlm.nih.gov

[MECHOP-BM chemotherapy in the treatment of non Hodgkin's lymphoma]. [2006]

10. China pubmed.ncbi.nlm.nih.gov

[Tolerance and pharmacodynamics phase Ⅰ clinical trial study of chimeric anti-CD20 monoclonal antibody IBI301 in Chinese patients with CD20-positive non-Hodgkin's lymphoma]. [2020]

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

Oral etoposide in lymphoma. [2018]

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

ESHAP as salvage therapy for refractory non-Hodgkin's lymphoma: Taiwan experience. [2019]

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

E-SHAP: inadequate treatment for poor-prognosis recurrent lymphoma. [2020]