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

Recruiting at 18 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

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

What data supports the effectiveness of the drug combination Lenalidomide + EPOCH Chemotherapy for Adult T-Cell Leukemia-Lymphoma?

The modified EPOCH regimen, which includes some of the same drugs as the Lenalidomide + EPOCH combination, has shown effectiveness in treating aggressive adult T-cell leukemia/lymphoma, with patients achieving complete or partial remission. Additionally, lenalidomide has been approved for use in relapsed or refractory cases of this disease, suggesting potential benefits when combined with EPOCH chemotherapy. ^{1 2 3 4 5}

Is the combination of Lenalidomide and EPOCH chemotherapy safe for humans?

The EPOCH chemotherapy regimen, which includes drugs like cyclophosphamide, doxorubicin, etoposide, vincristine, and prednisone, has been studied for various lymphomas and leukemia. Common side effects include low blood cell counts, nausea, vomiting, constipation, and infections, but these are generally manageable with supportive care. Lenalidomide, used for T-cell lymphomas, has manageable toxicity, with serious side effects mainly affecting blood cells, but these are reversible. ^{6 7 8 9 10}

What makes the Lenalidomide + EPOCH chemotherapy treatment unique for adult T-cell leukemia-lymphoma?

This treatment combines lenalidomide, which has unique immune-boosting and anti-cancer effects, with the EPOCH chemotherapy regimen, potentially offering a novel approach for aggressive adult T-cell leukemia-lymphoma, especially for patients who may not respond well to standard therapies. ^{1 9 11 12 13}

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of lenalidomide when given together with usual combination chemotherapy (etoposide, prednisone, vincristine sulfate \[Oncovin\], cyclophosphamide, and doxorubicin hydrochloride \[hydroxydaunorubicin hydrochloride\], or "EPOCH") in treating adult T-cell leukemia-lymphoma. Lenalidomide may help shrink or slow the growth of adult T-cell leukemia-lymphoma. Drugs used in chemotherapy, such as etoposide, vincristine, cyclophosphamide, and doxorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Anti-inflammatory drugs such as prednisone lower the body's immune response and are used with other drugs in the treatment of some types of cancer. Giving lenalidomide and the usual combination chemotherapy may work better in treating adult T-cell leukemia-lymphoma compared to the usual combination chemotherapy alone.

Research Team

Lee Ratner

Principal Investigator

Yale University Cancer Center LAO

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2021]

2. Italy 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. [2018]

3. United States 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. [2019]

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

VCAP-AMP-VECP compared with biweekly CHOP for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group Study JCOG9801. [2021]

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

An update on the developments in the treatment of adult T-cell leukemia-lymphoma: current knowledge and future perspective. [2023]

6. Japan pubmed.ncbi.nlm.nih.gov

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

7. United States 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. [2019]

8. 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]

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

Role of lenalidomide in the treatment of peripheral T-cell non-Hodgkin lymphomas. [2021]

10. Italy pubmed.ncbi.nlm.nih.gov

Dose-adjusted EPOCH chemotherapy for untreated peripheral T-cell lymphomas: a multicenter phase II trial of West-JHOG PTCL0707. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Effective maintenance treatment with lenalidomide for a patient with aggressive adult T cell leukemia after chemotherapy. [2022]

12. Japan pubmed.ncbi.nlm.nih.gov

EPOCH regimen as salvage therapy for adult T-cell leukemia-lymphoma. [2018]

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

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