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

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to determine if lenalidomide, combined with common chemotherapy drugs, can effectively treat primary effusion lymphoma (PEL), a rare cancer. Participants will receive a combination of lenalidomide and various chemotherapy drugs to evaluate the treatment's effectiveness. Individuals over 18 with PEL may qualify for this trial. As a Phase 1, Phase 2 trial, the research focuses on understanding the treatment's effects and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment research.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining lenalidomide with chemotherapy drugs such as rituximab, prednisone, etoposide, doxorubicin, vincristine, and cyclophosphamide has been tested in people with lymphoma. Studies have found this treatment to be generally well-tolerated. For instance, some patients with various types of lymphoma have used similar drug combinations without major issues.

However, like all cancer treatments, side effects can occur. These may include common issues such as tiredness, nausea, or low blood counts. Participants should maintain communication with their healthcare team to manage any side effects. Overall, early findings suggest the treatment is safe enough for further research, which is why this trial is being conducted. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lymphoma?

Researchers are excited about this treatment for lymphoma because it combines several potent drugs, including lenalidomide, which has unique immune-modulating properties. Unlike standard chemotherapy regimens like CHOP (Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone), this treatment adds lenalidomide and rituximab, a targeted therapy, to potentially enhance the immune system's ability to fight cancer cells. This combination aims to improve effectiveness by targeting cancer cells more precisely and reducing the likelihood of resistance that can occur with traditional treatments alone.

What evidence suggests that this trial's treatments could be effective for lymphoma?

Studies have shown that the drug combination in this trial, particularly the DA-R-EPOCH regimen, works well for certain lymphomas, such as diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBL). Research indicates that this regimen, which includes rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin, can be highly effective. In this trial, participants will receive this combination along with lenalidomide. Lenalidomide has been used successfully with similar drug combinations and shows promise in improving survival rates. These findings suggest that this drug mix could potentially treat primary effusion lymphoma (PEL) effectively, although this specific combination is still under study for PEL. The use of lenalidomide with these chemotherapy drugs aims to target and kill cancer cells more effectively. ^{1 2 3 5 6}

Who Is on the Research Team?

Ramya Ramaswami, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

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.

I haven't used cancer drugs in the last 2 weeks, except for rituximab or steroids.

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

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Lenalidomide, Rituximab, Prednisone, Etoposide, Doxorubicin, Vincristine and Cyclophosphamide Experimental Treatment 17 Interventions

Lenalidomide, Rituximab, Prednisone, Etoposide, 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+

Published Research Related to This Trial

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]

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 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 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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9036549/

DA-R-EPOCH vs R-CHOP in DLBCL: How Do We Choose? One regimen in particular that has emerged is dose-adjusted rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-R-EPOCH), an ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02911142

Lenalidomide Combined With Modified DA-EPOCH and ... (Phase II) Overall Survival in Treatment-naive Participants With Primary Effusion Lymphoma Treated With Etoposide, Prednisone, Vincristine, Cyclophosphamide, ...

3. cda-amc.ca cda-amc.ca/sites/default/files/pdf/htis/2021/RC1392-R2-RR-NHL_Final.pdf

Lenalidomide Plus Rituximab Chemotherapy for Relapsed ... No evidence was identified by this review describing rituximab, fludarabine, cyclophosphamide, mitoxantrone (R-FCM); rituximab, cyclophosphamide ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8464592/

Lenalidomide in combination with R-CHOP produces high ... Outcomes of transformed and concurrent DLBCL treated with dose-escalated etoposide, cyclophosphamide, doxorubicin, and vincristine with prednisone and rituximab ...

5. bloodcancerstoday.com bloodcancerstoday.com/post/real-world-data-show-r-da-epoch-treatment-is-highly-effective-therapy-for-pmbl

R-DA-EPOCH is 'Highly Effective Therapy' for PMBL A real-world study showed R-DA-EPOCH is a “highly effective regimen” to treat primary mediastinal large B-cell lymphoma (PMBL).

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4202129/

Clinical outcomes of a novel combination of lenalidomide ... Seven of the patients (18%) received acytotoxic chemotherapy regimen, including hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone( ...