Lenalidomide + EPOCH-R for Lymphoma

Overseen By Kathryn A Lurain, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Lenalidomide, DA-EPOCH-R

Must not be taking: Systemic anticancer treatments

Disqualifiers: Brain involvement, Renal dysfunction, Hepatic dysfunction, others

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

Compensation: Varies

Number of Visits: 1

Duration: 18 weeks

12 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use other systemic anticancer treatments or agents within the past 2 weeks before starting the trial, except for rituximab or steroids.

What data supports the effectiveness of the drug Lenalidomide + EPOCH-R for Lymphoma?

Research shows that the DA-EPOCH-R regimen, which includes many of the same drugs as Lenalidomide + EPOCH-R, has been effective in treating diffuse large B-cell lymphoma, with improved progression-free survival rates compared to other treatments. Additionally, lenalidomide has shown clinical activity in other conditions like multiple myeloma, suggesting potential benefits in combination therapies. ^{1 2 3 4 5}

Is the combination of Lenalidomide with EPOCH-R safe for treating lymphoma?

The combination of Lenalidomide with cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab has been studied in elderly patients with diffuse large B-cell lymphoma and was found to be generally safe, with manageable side effects like neutropenia (low white blood cell count), thrombocytopenia (low platelet count), and anemia (low red blood cell count). Other non-blood-related side effects were moderate, including some heart and nerve issues. ^{2 4 5 6 7}

What makes the Lenalidomide + EPOCH-R treatment unique for lymphoma?

The Lenalidomide + EPOCH-R treatment is unique because it combines lenalidomide with the DA-EPOCH-R regimen, which has shown promising results in treating aggressive lymphomas without the need for radiotherapy. This combination aims to enhance the effectiveness of the treatment by adding lenalidomide, which has immune-modulating properties, to the already effective DA-EPOCH-R regimen. ^{3 5 8 9 10}

What is the purpose of this trial?

Background: Primary effusion lymphoma (PEL) is a rare disease with no standard treatment. Researchers want to see if a drug called lenalidomide along with common chemotherapy drugs may be effective in treating PEL. Objective: To test a new treatment for PEL. Eligibility: People ages 18 and older with PEL. Design: Participants will be screened with blood tests, imaging studies, a physical exam, and other tests. Participants will have tests to evaluate their disease. These may include: Blood tests Scans Lumbar puncture. Fluid around the spinal cord will be removed with a needle. Bone marrow removed with a needle and studied Samples of skin or lymph nodes removed Fluid removed from around organs Lung and eye tests Tubes with cameras taking pictures of airways or digestive tract Participants will take lenalidomide pills for 10 days. They will keep a pill diary. Participants will have a catheter (small tube) placed in the large vein in the arm or chest. Participants will get DA-EPOCH-R as intravenous infusions by catheter over several days. This will be repeated in 21-day cycles. Most participants will have 6 cycles. Participants will get the drug filgrastim by injection under the skin. They will get the drug methotrexate injected into the spinal fluid. During the study, participants will have the following tests done at least once: Medical history Physical exam Blood, urine, and stool tests Lesions photographed and measured Lumbar puncture Participants will have follow-up visits for 5 years. They will repeat the screening tests plus have urine and stool tested. Participants may be contacted later by phone to see how they are doing.

Research Team

Kathryn A Lurain, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults with primary effusion lymphoma (PEL) or KSHV-associated large cell lymphoma can join this trial. They must have measurable or assessable lymphoma, any HIV status, and be able to take daily aspirin or a substitute. Women of childbearing age must test negative for pregnancy and use two forms of birth control; men must use condoms. Participants cannot have had certain other cancer treatments recently, severe illnesses that could interfere with the study, poor organ function related to conditions other than their lymphoma, or known allergies to similar drugs.

Inclusion Criteria

All study participants must agree to be registered into the mandatory REVLIMID REMS program, and be willing and able to comply with the requirements of the REVLIMID REMS program

I can take aspirin daily or a substitute if I'm allergic.

Ability of subject to understand and the willingness to sign a written informed consent document

Exclusion Criteria

My kidney function is low, with a creatinine clearance under 60 mL/min.

You have experienced severe allergic reactions to thalidomide, lenalidomide, or pomalidomide in the past, including a specific type of rash called erythema nodosum.

Any condition, including laboratory abnormalities, which in the opinion of the Principal Investigator or Lead Associate Investigator, would prohibit administration of planned chemotherapeutic intervention, places the subject at unacceptable risk if they were to participate in the study or confounds the ability to interpret data from the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive lenalidomide pills for 10 days and DA-EPOCH-R as intravenous infusions in 21-day cycles, repeated for up to 6 cycles

18 weeks

Multiple visits (in-person) for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits for 5 years

5 years

Regular follow-up visits (in-person)

Treatment Details

Interventions

• Cyclophosphamide
• Doxorubicin
• Etopside
• Lenalidomide
• Prednisone
• Rituximab
• Vincristine

Trial Overview The trial is testing lenalidomide pills combined with DA-EPOCH-R chemotherapy given through a catheter over several days in cycles lasting 21 days each. Most participants will undergo six cycles. Additional medications like filgrastim and methotrexate are also part of the treatment regimen. The effectiveness of this combination therapy against PEL is being evaluated.

Participant Groups

Group I: 1 Experimental Treatment 7 Interventions

Lenalidomide, Rituximab, Prednisone, Etopiside, Doxorubicin, Vincristine and Cyclophosphamide

Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a phase III study involving 491 patients with diffuse large B-cell lymphoma, the more intensive treatment regimen DA-EPOCH-R did not show a statistically significant improvement in progression-free survival (PFS) or overall survival (OS) compared to the standard R-CHOP regimen, with 2-year PFS rates of 78.9% for DA-EPOCH-R and 75.5% for R-CHOP.

DA-EPOCH-R was associated with a higher incidence of severe adverse events, including infections and febrile neutropenia, indicating that while it is a more intensive treatment, it does not provide additional survival benefits and carries greater risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303. Bartlett, NL., Wilson, WH., Jung, SH., et al.[2021]

In a study of 20 patients with untreated poor prognosis diffuse large B-cell lymphoma (DLBCL), the two-weekly dose-adjusted EPOCH-like chemotherapy (DA-EDOCH14-R) showed a promising three-year progression-free survival (PFS) rate of 95%, compared to 74% in a previous trial with a three-weekly regimen.

The treatment was well-tolerated with manageable toxicity and no therapy-related deaths, highlighting its safety, especially for patients with a high-risk prognosis (age-adjusted International Prognostic Index of 3), where PFS reached 100% compared to just 30% in the previous trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-weekly dose-adjusted (DA)-EPOCH-like chemotherapy with high-dose dexamethasone plus rituximab (DA-EDOCH14-R) in poor-prognostic untreated diffuse large B-cell lymphoma. García-Suárez, J., Flores, E., Callejas, M., et al.[2015]

In a study of 136 patients with aggressive non-Hodgkin lymphoma treated with dose-adjusted EPOCH chemotherapy, the overall response rate was 82%, indicating that this treatment is effective for both B- and T-cell types of the disease.

Factors such as current smoking, presence of disease in the bone marrow, and the number of treatment cycles completed were identified as independent predictors of death and relapse, highlighting the importance of these factors in patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-Adjusted Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (EPOCH) With or Without Rituximab as First-Line Therapy for Aggressive Non-Hodgkin Lymphoma. Lamar, ZS., Fino, N., Palmer, J., et al.[2018]

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]

In a phase I study involving 21 elderly patients with untreated diffuse large B-cell lymphoma, the combination of lenalidomide and standard chemotherapy resulted in a high overall response rate of 90%, with 81% achieving complete remission.

The maximum tolerated dose of lenalidomide was determined to be 15 mg/day, with manageable safety concerns, including hematologic toxicities like neutropenia in 28% of treatment courses, indicating that this regimen is safe for elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide plus cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab is safe and effective in untreated, elderly patients with diffuse large B-cell lymphoma: a phase I study by the Fondazione Italiana Linfomi. Chiappella, A., Tucci, A., Castellino, A., et al.[2021]

Lenalidomide is an effective oral treatment for various hematologic malignancies, including chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), with different starting doses based on the type of cancer.

Common side effects like neutropenia and thrombocytopenia can be managed effectively with proper monitoring and prophylaxis, allowing for safer administration and improved patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approaches to Managing Safety With Lenalidomide in Hematologic Malignancies. Blumel, S., Broadway-Duren, J.[2020]

EPOCH therapy, which includes continuous infusion of doxorubicin, vincristine, and etoposide, showed effectiveness in patients with refractory or relapsed non-Hodgkin's lymphoma and acute leukemias, with two patients achieving complete remission and three achieving partial remission out of 21 assessed.

While the treatment caused significant hematological toxicities like neutropenia and anemia in a majority of patients, these side effects were manageable with supportive care, suggesting that EPOCH therapy can be a viable option for patients resistant to previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[EPOCH therapy for relapsed/refractory lymphoid malignancies]. Dobashi, N., Usui, N., Kobayashi, T., et al.[2015]

In a multi-institutional study of 69 patients with untreated diffuse large B-cell lymphoma, the DA-EPOCH-R treatment showed high rates of progression-free survival (81%) and overall survival (84%) after a median follow-up of 62 months.

The treatment was well-tolerated, with no significant grade 4 non-hematologic toxicities reported, confirming its safety and efficacy across different subtypes of diffuse large B-cell lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Cancer and Leukemia Group B multi-center study of DA-EPOCH-rituximab in untreated diffuse large B-cell lymphoma with analysis of outcome by molecular subtype. Wilson, WH., Jung, SH., Porcu, P., et al.[2022]

References

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

Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Two-weekly dose-adjusted (DA)-EPOCH-like chemotherapy with high-dose dexamethasone plus rituximab (DA-EDOCH14-R) in poor-prognostic untreated diffuse large B-cell lymphoma. [2015]

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

Dose-Adjusted Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (EPOCH) With or Without Rituximab as First-Line Therapy for Aggressive Non-Hodgkin Lymphoma. [2018]

4. Japan pubmed.ncbi.nlm.nih.gov

A phase I, open-label, dose-escalation study of amrubicin in combination with lenalidomide and weekly dexamethasone in previously treated adults with relapsed or refractory multiple myeloma. [2022]

5. 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]

6. Italy pubmed.ncbi.nlm.nih.gov

Lenalidomide plus cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab is safe and effective in untreated, elderly patients with diffuse large B-cell lymphoma: a phase I study by the Fondazione Italiana Linfomi. [2021]

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

Approaches to Managing Safety With Lenalidomide in Hematologic Malignancies. [2020]

8. Japan pubmed.ncbi.nlm.nih.gov

[EPOCH therapy for relapsed/refractory lymphoid malignancies]. [2015]

9. Italy pubmed.ncbi.nlm.nih.gov

A Cancer and Leukemia Group B multi-center study of DA-EPOCH-rituximab in untreated diffuse large B-cell lymphoma with analysis of outcome by molecular subtype. [2022]

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

Dose-Adjusted Etoposide, Doxorubicin, and Cyclophosphamide With Vincristine and Prednisone Plus Rituximab Therapy in Children and Adolescents With Primary Mediastinal B-Cell Lymphoma: A Multicenter Phase II Trial. [2023]