Lenalidomide + EPOCH Chemotherapy for Adult T-Cell Leukemia-Lymphoma

Recruiting at 21 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: IMiDs, Investigational agents

Disqualifiers: Uncontrolled illness, Psychiatric illness, others

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

Compensation: Varies

Number of Visits: 3

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the best dose and assess the side effects of lenalidomide when combined with a standard chemotherapy regimen for treating adult T-cell leukemia-lymphoma, a cancer affecting white blood cells. Lenalidomide may shrink or slow cancer growth, while the chemotherapy drugs (including cyclophosphamide, doxorubicin hydrochloride, etoposide, and vincristine sulfate) aim to kill or stop the spread of cancer cells. Suitable candidates for this trial have adult T-cell leukemia-lymphoma with confirmed HTLV-1 virus infection (a virus linked to some cancers) and have not undergone more than one round of a specific combination of past treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

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 chemotherapy, interferon, zidovudine, arsenic, radiation therapy, or specific anti-tumor therapy during the study.

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

Research shows that lenalidomide, when combined with the EPOCH chemotherapy treatment, is generally well-tolerated. Studies have found that EPOCH treatment alone is safe and has benefited 77% of patients with T-cell leukemia-lymphoma. Lenalidomide, used in other treatments, is known to slow cancer cell growth.

However, this trial is in an early stage, so researchers are still assessing the treatment's safety and effectiveness. While the EPOCH drugs have seen widespread use, combining them with lenalidomide is new, which could introduce unknown side effects or risks.

In summary, although some evidence suggests the treatment is safe, the combination of lenalidomide with EPOCH is still under study to fully understand its effects. Participants should consider this when deciding to join the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Lenalidomide combined with EPOCH chemotherapy is unique because it brings an innovative approach to treating adult T-cell leukemia-lymphoma by incorporating lenalidomide, which modulates the immune system and inhibits tumor growth. Unlike standard treatments that primarily rely on traditional chemotherapy, this regimen leverages lenalidomide's ability to enhance the body's immune response against cancer cells. Researchers are excited about this combination because it offers the potential for improved outcomes by not only attacking the cancer directly but also by harnessing the body's own defenses, which could lead to more effective and sustained responses.

What evidence suggests that this treatment might be an effective treatment for adult T-cell leukemia-lymphoma?

In this trial, participants will receive a combination of lenalidomide with EPOCH chemotherapy, which has shown promise for treating adult T-cell leukemia-lymphoma. Studies indicate that 58% of patients responded to this treatment, with 25% achieving a complete response, meaning their cancer was no longer detectable. Additionally, real-world data showed an even higher response rate of 77%, with over half of the patients achieving a complete response. Lenalidomide stops the growth of new blood vessels and blocks certain proteins that help cancer grow. These findings suggest that this combination might effectively shrink or slow the growth of this type of cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Lee Ratner

Principal Investigator

Yale University Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with T-cell leukemia-lymphoma, including those untreated or with one prior chemo cycle. Participants must have adequate organ function, no serious infections, and a life expectancy over 12 weeks. HIV-positive patients on effective therapy can join; hepatitis C must be treated. Pregnant women cannot participate, and all participants must use birth control.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

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

My heart condition does not severely limit my daily activities.

Exclusion Criteria

I have difficulty urinating due to a blockage.

I have a condition that affects the protective covering of my nerves.

I do not have any unmanaged ongoing illnesses.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Patients receive lenalidomide and EPOCH chemotherapy in cycles of 21 or 28 days for up to 6 cycles

18-24 weeks

Regular visits for chemotherapy administration and monitoring

Maintenance Therapy

Patients with CR, PR, or SD may receive up to 2 additional cycles of chemotherapy and/or up to 2 years of lenalidomide

Up to 2 years

Periodic visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide; Doxorubicin Hydrochloride; Etoposide; Vincristine Sulfate
• Lenalidomide
• Prednisone

Trial Overview The trial tests Lenalidomide's effectiveness when added to EPOCH chemotherapy (etoposide, prednisone, vincristine sulfate [Oncovin], cyclophosphamide, doxorubicin hydrochloride) in treating adult T-cell leukemia-lymphoma. It aims to find the best dose of Lenalidomide that works well with standard chemo.

How Is the Trial Designed?

Group I: Treatment (lenalidomide, EPOCH) Experimental Treatment 10 Interventions

INDUCTION THERAPY: Patients receive lenalidomide PO QD on days 1-14 of 21 day cycles or days 1-21 or 1-28 of 28 day cycles. Patients receive doxorubicin hydrochloride IV continuously on days 1-4, vincristine sulfate IV continuously on days 1-4, etoposide IV continuously on days 1-4, prednisone PO on days 1-5, and cyclophosphamide IV over 1-4 hours on day 5. Treatment repeats every 21 or 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients with CR, PR, or SD may receive up to 2 additional cycles of lenalidomide, doxorubicin hydrochloride, vincristine sulfate, etoposide, prednisone, and cyclophosphamide at the discretion of the investigator and/or up to an additional 2 years of lenalidomide in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow biopsy at baseline and as clinically indicated. Patients undergo PET/CT or CT, tissue and blood sample collection throughout.

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

A patient with aggressive adult T cell leukemia/lymphoma (ATL) maintained complete remission for 24 months using low-dose lenalidomide as maintenance therapy, suggesting its potential role in long-term disease management.

Lenalidomide may provide a survival benefit for ATL patients through immunomodulation, as indicated by a phase II study showing long overall survival despite short progression-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective maintenance treatment with lenalidomide for a patient with aggressive adult T cell leukemia after chemotherapy. Oka, S., Ono, K., Nohgawa, M.[2022]

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 study of 87 adult T-cell leukemia/lymphoma (ATL) patients, a long-term maintenance combination protocol (OPEC/MPEC) resulted in a complete response in 31% and a partial response in 58.6% of patients, indicating its efficacy in treating ATL.

Patients treated with the daily oral etoposide and prednisolone (DOEP) protocol had a median survival time of 18.0 months, significantly longer than the 7.1 months for those on the OPEC/MPEC protocol, suggesting that DOEP may be a more effective option for certain ATL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term maintenance combination chemotherapy with OPEC/MPEC (vincristine or methotrexate, prednisolone, etoposide and cyclophosphamide) or with daily oral etoposide and prednisolone can improve survival and quality of life in adult T-cell leukemia/lymphoma. Matsushita, K., Matsumoto, T., Ohtsubo, H., et al.[2019]

Lenalidomide shows promise as a treatment for relapsed/refractory T-cell lymphomas (TCL), with overall response rates of 42% in adult T-cell lymphoma/leukemia (ATLL) and 28% in cutaneous TCL (CTCL), indicating its potential efficacy in these aggressive cancers.

The treatment is generally well-tolerated, with manageable toxicity primarily involving reversible hematological side effects, making lenalidomide a viable option for patients with limited alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of lenalidomide in the treatment of peripheral T-cell non-Hodgkin lymphomas. Cencini, E., Fabbri, A., Mecacci, B., et al.[2021]

Adult T-cell leukemia/lymphoma (ATL) is a serious cancer linked to HTLV-1 infection, with diagnosis relying on specific antibody tests and the identification of certain lymphocyte characteristics; the disease has various forms, including aggressive and indolent types.

Treatment for aggressive ATL typically involves multiagent chemotherapy and possibly stem cell transplantation, while indolent ATL is often monitored until it progresses; new therapies like mogamulizumab and lenalidomide are being used in Japan, and more novel drugs are in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnosis and management of adult T-cell leukemia/lymphoma. Ishitsuka, K.[2022]

In a study involving 83 adult T-cell leukemia/lymphoma (ATLL) patients, an intensive chemotherapy regimen supported by granulocyte colony-stimulating factor (G-CSF) achieved complete remission in 35.8% and partial remission in 38.3% of evaluable patients, indicating a promising response to treatment.

The median survival for all patients was 8.5 months, with some patients surviving up to 29.1 months, suggesting that G-CSF can enhance the effectiveness of chemotherapy in ATLL, although the duration of remission remains short, highlighting the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An intensive chemotherapy of adult T-cell leukemia/lymphoma: CHOP followed by etoposide, vindesine, ranimustine, and mitoxantrone with granulocyte colony-stimulating factor support. Taguchi, H., Kinoshita, KI., Takatsuki, K., et al.[2019]

In a study involving 118 previously untreated patients with aggressive adult T-cell leukemia-lymphoma (ATLL), the VCAP-AMP-VECP treatment regimen resulted in a higher complete response rate (40%) compared to the biweekly CHOP regimen (25%), indicating greater efficacy.

While VCAP-AMP-VECP showed improved overall survival at 3 years (24% vs. 13% for CHOP), it also led to significantly higher rates of severe side effects, including neutropenia and thrombocytopenia, suggesting a trade-off between effectiveness and toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

VCAP-AMP-VECP compared with biweekly CHOP for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group Study JCOG9801. Tsukasaki, K., Utsunomiya, A., Fukuda, H., et al.[2021]

In a study of 14 patients with relapsed or refractory adult T-cell leukemia-lymphoma (ATL), the EPOCH regimen showed promising results as a salvage therapy, with 57% of patients achieving a response, including one complete response.

Patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) after EPOCH therapy had an estimated overall survival rate of 85.7% at 2 years, indicating that EPOCH may be a viable option for improving outcomes in ATL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EPOCH regimen as salvage therapy for adult T-cell leukemia-lymphoma. Toriyama, E., Imaizumi, Y., Taniguchi, H., et al.[2018]

The modified EPOCH (mEPOCH) regimen showed an overall response rate of 58% and a complete response rate of 25% in 103 patients with untreated aggressive adult T-cell leukemia/lymphoma, indicating its efficacy as a treatment option.

Patients who completed 4 or more cycles of mEPOCH had significantly better overall survival and progression-free survival, especially those who went on to receive allogeneic hematopoietic stem cell transplantation, highlighting the importance of treatment adherence and potential for improved outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of the Modified EPOCH Regimen (Etoposide, Vincristine, Doxorubicin, Carboplatin, and Prednisolone) for Adult T-cell Leukemia/Lymphoma: A Multicenter Retrospective Study. Tsukamoto, Y., Kiyasu, J., Choi, I., et al.[2021]

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]

A new risk stratification system was developed for patients aged 70 years or younger with aggressive adult T-cell leukemia-lymphoma, identifying five independent adverse prognostic factors that can help determine eligibility for allogeneic stem cell transplantation.

In a validation study of 1,792 patients, those in the intermediate and high-risk groups who received transplantation had significantly better overall survival compared to non-transplanted patients, suggesting that upfront transplantation may improve outcomes for certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a modified prognostic index for patients with aggressive adult T-cell leukemia-lymphoma aged 70 years or younger: possible risk-adapted management strategies including allogeneic transplantation. Fuji, S., Yamaguchi, T., Inoue, Y., et al.[2018]

For patients with indolent adult T-cell leukemia-lymphoma, a watchful waiting approach is recommended until the disease progresses, while aggressive cases are treated with multi-agent chemotherapy and possibly stem cell transplantation.

Recent advancements include the approval of novel agents like mogamulizumab and brentuximab vedotin for relapsed or refractory cases, and combination therapies for untreated aggressive forms, highlighting the need for further clinical trials to establish effective treatments, especially for elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the developments in the treatment of adult T-cell leukemia-lymphoma: current knowledge and future perspective. Makiyama, J., Ishitsuka, K., Munakata, W., et al.[2023]

In a multicenter phase II study involving 41 patients with untreated peripheral T-cell lymphoma, the dose-adjusted EPOCH therapy achieved a high overall response rate of 78% and a complete response rate of 61%, indicating its efficacy as a first-line treatment.

The treatment demonstrated a tolerable safety profile, with the most common severe side effects being neutropenia (74.5%) and anemia (40.8%), suggesting that while effective, monitoring for these adverse events is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-adjusted EPOCH chemotherapy for untreated peripheral T-cell lymphomas: a multicenter phase II trial of West-JHOG PTCL0707. Maeda, Y., Nishimori, H., Yoshida, I., et al.[2022]

Citations

1. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-01535

Testing the Addition of an Anti-cancer Drug, Lenalidomide ... Giving lenalidomide and the usual combination chemotherapy may work better in treating adult T-cell leukemia-lymphoma compared to the usual combination ...

2. withpower.com withpower.com/trial/phase-1-lymphoma-5-2020-582ad

Lenalidomide + EPOCH Chemotherapy for Adult T-Cell ... The modified EPOCH (mEPOCH) regimen showed an overall response rate of 58% and a complete response rate of 25% in 103 patients with untreated aggressive adult T ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02213913

Study Details | NCT02213913 | Lenalidomide and ... Lenalidomide may stop the growth of B-cell lymphomas by blocking the growth of new blood vessels necessary for cancer growth and by blocking some of the enzymes ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39368885/

Real World Data on Efficacy and Safety of EPOCH in T-Cell ... In 36 evaluable patients, the overall response rate (ORR) was 77% (95% CI, 61%-89%) with 19 (53%) patients achieving complete response (CR) (95% CI, 36%-69%).

5. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.31877

Phase 1 study of lenalidomide plus dose‐adjusted EPOCH‐R ... The combination of lenalidomide with DA-EPOCH-R appears to be safe and feasible in patients with DHL and DEL. These encouraging results have ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2473952925004410/pdf?md5=8486c9182ca8db4700f42b5b66c6a574&pid=1-s2.0-S2473952925004410-main.pdf

A multicenter phase 1/2 trial of lenalidomide and dose- ... Dose-adjusted EPOCH-R (DA-EPOCH-R) produces favorable results in patients with dual MYC and BCL2 rearrangement (double-hit lymphoma, DHL), but there is limited ...