Adult T-Cell Leukemia/Lymphoma > Cyclophosphamide; Doxorubicin Hydrochloride; Etoposide; Vincristine Sulfate
Lenalidomide + EPOCH Chemotherapy for Adult T-Cell Leukemia-Lymphoma
Recruiting in Palo Alto (17 mi)
+16 other locations
Overseen ByLee Ratner
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: National Cancer Institute (NCI)
Must not be taking: IMiDs, Investigational agents
Disqualifiers: Uncontrolled illness, Psychiatric illness, others
No Placebo Group
Trial Summary
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.
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.
12345Is 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.
678910What 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.
19111213Eligibility 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.
I am 18 years old or older.
My heart condition does not severely limit my daily activities.
I am able to become pregnant and will use birth control and have a negative pregnancy test.
I do not have any serious infections requiring treatment right now.
I have chronic hepatitis B but it's under control with medication.
I had hepatitis C but am now cured or have no detectable virus while on treatment.
I have been treated with AZT, IFN, bexarotene, or mogamulizumab before.
My cancer is a type of ATLL and tests positive for CD2, CD3, or CD4.
I have confirmed HTLV infection through tests.
I am not on any other cancer treatments during this study.
My kidney function tests are within normal limits.
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.
I have been treated with IMiDs for my ATLL.
I cannot take aspirin or certain blood thinners.
I have recovered from major side effects of previous cancer treatments.
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Treatment (lenalidomide, EPOCH)Experimental Treatment10 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.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Memorial Sloan Kettering MonmouthMiddletown, NJ
Ohio State University Comprehensive Cancer CenterColumbus, OH
Emory University Hospital/Winship Cancer InstituteAtlanta, GA
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer CenterNew York, NY
More Trial Locations
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Who is running the clinical trial?
National Cancer Institute (NCI)Lead Sponsor
References
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]We retrospectively analyzed patients with untreated aggressive adult T-cell leukemia/lymphoma who received the modified EPOCH (mEPOCH) regimen.
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]Adult T-cell leukemia-lymphoma is a distinct type of peripheral T-cell lymphoma caused by human T-cell lymphotropic virus type I. Although allogeneic stem cell transplantation after chemotherapy is a recommended treatment option for patients with aggressive adult T-cell leukemia-lymphoma, there is no consensus about indications for allogeneic stem cell transplantation because there is no established risk stratification system for transplant eligible patients. We conducted a nationwide survey of patients with aggressive adult T-cell leukemia-lymphoma in order to construct a new, large database that includes 1,792 patients aged 70 years or younger with aggressive adult T-cell leukemia-lymphoma who were diagnosed between 2000 and 2013 and received intensive first-line chemotherapy. We randomly divided patients into two groups (training and validation sets). Acute type, poor performance status, high soluble interleukin-2 receptor levels (> 5,000 U/mL), high adjusted calcium levels (≥ 12 mg/dL), and high C-reactive protein levels (≥ 2.5 mg/dL) were independent adverse prognostic factors used in the training set. We used these five variables to divide patients into three risk groups. In the validation set, median overall survival for the low-, intermediate-, and high-risk groups was 626 days, 322 days, and 197 days, respectively. In the intermediate- and high-risk groups, transplanted recipients had significantly better overall survival than non-transplanted patients. We developed a promising new risk stratification system to identify patients aged 70 years or younger with aggressive adult T-cell leukemia-lymphoma who may benefit from upfront allogeneic stem cell transplantation. Prospective studies are warranted to confirm the benefit of this treatment strategy.
An intensive chemotherapy of adult T-cell leukemia/lymphoma: CHOP followed by etoposide, vindesine, ranimustine, and mitoxantrone with granulocyte colony-stimulating factor support. [2019]An intensive combination chemotherapy regimen supported by granulocyte colony-stimulating factor (G-CSF) was evaluated in adult T-cell leukemia/lymphoma (ATLL) patients in a multiinstitutional, cooperative study. Vincristine 1 mg/m2 i.v. day 1, Adriamycin 40 mg/m2 i.v. day 1, cyclophosphamide 400 mg/m2 i.v. day 1, prednisolone 40 mg/m2 i.v. days 1 to 3 and 8 to 10, etoposide 35 mg/m2 i.v. days 1 to 8, vindesine 2 mg/m2 i.v. day 8, ranimustine 50 mg/m2 i.v. day 8, mitoxantrone 7 mg/m2 i.v. day 8, and G-CSF 50 mg/m2 s.c. days 9 to 21 were given for 2 to 4 courses every 3 weeks to 83 patients with ATLL. Complete remission (CR) and partial remission (PR) were achieved in 35.8 and 38.3 percent, respectively, of 81 evaluable patients. The median survival of all patients was 8.5 months, with a predicted 3-year survival of 13.5 percent by the Kaplan-Meier method. The median duration of response was 7.6 months (range 0.2-42.7), and 13 patients were alive. Their median survival time was 29.1 months (range 19.2-44.7). In 67.6 percent of courses, white blood cell (WBC) nadirs were 1.0 x 10(9)/L were
VCAP-AMP-VECP compared with biweekly CHOP for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group Study JCOG9801. [2021]Our previous phase II trial for treating human T-lymphotropic virus type I-associated adult T-cell leukemia-lymphoma (ATLL) with vincristine, cyclophosphamide, doxorubicin, and prednisone (VCAP), doxorubicin, ranimustine, and prednisone (AMP), and vindesine, etoposide, carboplatin, and prednisone (VECP) showed promising results. To test the superiority of VCAP-AMP-VECP over biweekly cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), we conducted a randomized controlled trial exclusively for ATLL.
An update on the developments in the treatment of adult T-cell leukemia-lymphoma: current knowledge and future perspective. [2023]Adult T-cell leukemia-lymphoma is defined as peripheral T-cell lymphoma caused by the human T-cell leukemia virus type I. Adult T-cell leukemia-lymphoma is classified into indolent (favorable chronic or smoldering) or aggressive (acute, lymphoma or unfavorable chronic) types. This review discusses the therapeutic developments for patients with adult T-cell leukemia-lymphoma and unmet issues in treating adult T-cell leukemia-lymphoma. For indolent adult T-cell leukemia-lymphoma, a watchful waiting strategy is recommended until the disease progresses to aggressive adult T-cell leukemia-lymphoma. For aggressive adult T-cell leukemia-lymphoma, multi-agent chemotherapy with or without allogeneic hematopoietic stem cell transplantation has been recommended. However, many patients with adult T-cell leukemia-lymphoma relapse, and their prognosis is poor. Recently, novel agents, including mogamulizumab, lenalidomide, brentuximab vedotin, tucidinostat and valemetostat, have been approved for patients with relapsed or refractory aggressive adult T-cell leukemia-lymphoma, and the combination of mogamulizumab with multi-agent chemotherapy or brentuximab vedotin with cyclophosphamide, doxorubicin and prednisone has been approved for patients with untreated aggressive adult T-cell leukemia-lymphoma in Japan. Importantly, the aging of patients with adult T-cell leukemia-lymphoma has recently been reported, and no standard of care for elderly patients with adult T-cell leukemia-lymphoma has been established. New evidence must be obtained from prospective clinical trials to improve the prognosis of patients with adult T-cell leukemia-lymphoma.
[EPOCH therapy for relapsed/refractory lymphoid malignancies]. [2015]Patients with refractory or relapsed non-Hodgkin's lymphoma (NHL), acute T-cell leukemia (ATL), ATL lymphoma and acute lymphocytic leukemia (ALL) received EPOCH therapy. All were previously treated with doxorubicin (DOX), vincristine (VCR) and other drugs. The EPOCH treatment schedule is consisted with DOX (10 mg/M2/day, 5 days c.i.v.), VCR (0.4 mg/M2/day, 4 days c.i.v.), etoposide (50 mg/M2/day, 4 days c.i.v.), cyclophosphamide (750 mg/M2/day, day 6 i.v.) and prednisolone (60 mg/M2/day, 5 days p.o.). Twenty-one patients (ALL:10, NHL:8, ATLL:2, ATL:1) were assessable for response and toxicity. Two patients with ALL and NHL, respectively, achieved a complete remission and 3 patients obtained partial remission (NHL:2, ATLL:1). The hematological toxicity (grade > 1) included neutoropenia, anemia and thrombocytopenia, which were observed in 83.3%, 76.7% and 76.7% respectively, of total 30 EPOCH courses. The major non-hematological toxicities were nausea/vomiting, constipation and infection, but most of the toxicity were tolerable with sufficient clinical supportive care. These results indicate that continuous infusion of DOX, VCR and ETP might be effective in patients who were treated with, and presumed to be resistant to the same drugs administrated by bolus infusion.
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]Acute leukemia and lymphoma varieties of adult T-cell leukemia/lymphoma (ATL) usually carry a poor prognosis. While etoposide is generally useful for treating ATL, especially as a daily oral maintenance regimen, etoposide has not proven effective in severe types of ATL efficient in some patients. Of 87 ATL patients whom we have treated, 51 had acute leukemia, 22 lymphoma and 14 progressive chronic leukemia. Seventy-nine patients were treated with a long term maintenance combination protocol, OPEC/MPEC (weekly doses of vincristine, 0.7 mg/m2 or methotrexate, 14 mg/m2; prednisolone, 20 mg/m2; etoposide, 70 mg/m2 and cyclophosphamide, 200 mg/m2). The other 8 patients, 3 with acute leukemia, 2 with lymphoma and 3 with progressive chronic leukemia, were treated with daily oral administration of 25 mg of etoposide and 10 mg of prednisolone (DOEP). The dose administered was modified in individual cases to maintain the granulocyte count and reduce the number of ATL cells. Considering both protocols, a complete response and a partial response were achieved in 31.0% and 58.6% patients, respectively. Median survival times (MST) of all patients and, acute leukemia, lymphoma and progressive chronic leukemia types were 7.5, 6.7, 9.6 and 12.4 months, respectively. Respective MST of patients treated with OPEC/MPEC or DOEP protocols were 7.1 and 18.0 months. Relatively normal WBC counts, lower lactate dehydrogenase concentration and normal calcium concentration, limited numbers of anatomic sites involved, good performance status and good response to chemotherapy were significantly associated with long survival time. Drug toxicity was not apparent, and about half of patients were treated in an outpatient setting.
Dose-Adjusted Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (EPOCH) With or Without Rituximab as First-Line Therapy for Aggressive Non-Hodgkin Lymphoma. [2018]Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) was developed in an effort to overcome inadequate drug concentrations and compensate for increased drug clearance. The goal of the present study was to examine the risk factors and outcomes of patients with aggressive non-Hodgkin lymphoma (aNHL) treated with DA-EPOCH.
Role of lenalidomide in the treatment of peripheral T-cell non-Hodgkin lymphomas. [2021]T-cell lymphomas (TCLs) represent a group of lymphoid neoplasms characterized by an aggressive clinical course, even after an anthracycline-containing regimen. Novel agents for patients with relapsed/refractory TCL are urgently needed. Lenalidomide is an oral drug with immunomodulatory, antiangiogenic and direct antineoplastic effects. These peculiar mechanisms of action make TCL an attractive target for lenalidomide. We have identified five clinical trials in which lenalidomide monotherapy was investigated to treat TCL, including cutaneous TCL (CTCL) and adult T-cell lymphoma/leukemia (ATLL). In the ATLL-002 study, the overall response rate (ORR) was 42% and median progression-free survival (PFS) and overall survival were 3.8 mo and 20.3 mo, respectively. In a phase II trial for CTCL, ORR was 28% and median PFS and overall survival were 8 mo and 43 mo, respectively. For nodal peripheral TCL, ORR was between 10% and 43% in three clinical trials, with a median PFS of about 4 mo, even if some patients had a durable response. Overall toxicity is manageable and grade 3-4 events are mainly hematological and reversible. Combination strategies did not improve PFS. In conclusion, lenalidomide could represent a suitable treatment option for relapsed/refractory TCL, especially for neoplasms with a T-follicular helper origin, such as angioimmunoblastic TCL.
Dose-adjusted EPOCH chemotherapy for untreated peripheral T-cell lymphomas: a multicenter phase II trial of West-JHOG PTCL0707. [2022]The standard CHOP therapy for peripheral T-cell lymphoma has resulted in unsatisfactory outcomes and it is still not clear what is the optimal front-line therapy. We conducted a multicenter phase II study of dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone (EPOCH) for untreated peripheral T-cell lymphoma patients. In this prospective study, 41 patients were treated with dose-adjusted-EPOCH as initial therapy: peripheral T-cell lymphoma-not otherwise specified, n=21; angioimmunoblastic T-cell lymphoma, n=17; anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, n=2; and anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, n=1. Median patient age was 64 years (range: 32-79 years). According to the International Prognostic Index criteria, 51.2% were at high-intermediate or high risk. The overall response and complete response rates were 78.0% [95% confidence interval (CI): 62.4-89.4%] and 61.0% (95%CI: 44.5-75.8%), respectively. At the median follow up of 24.0 months, the 2-year progression-free survival and overall survival were 53.3% (95%CI: 36.4-67.5%) and 73.2% (95%CI: 56.8-84.1%), respectively. The younger patients (≤ 60 years old) had a high response rate (overall response 94.1% and complete response 70.6%) and survival rate (progression-free survival 62.5% and overall survival 82.4%). The most common grade ≥ 3 adverse events were neutropenia (74.5%), anemia (40.8%), thrombocytopenia (22.0%), and febrile neutropenia (9.0%). Dose-adjusted-EPOCH had a high response rate with a tolerable toxicity profile. Our results indicate that dose-adjusted-EPOCH is a reasonable first-line approach for peripheral T-cell lymphoma patients and may improve outcomes.
Effective maintenance treatment with lenalidomide for a patient with aggressive adult T cell leukemia after chemotherapy. [2022]Adult T cell leukemia/lymphoma (ATL) is incurable with conventional chemotherapies, and allogeneic stem cell transplantation (SCT) is the only curative treatment. Direct antitumor effects and antitumor immune responses are important factors that need to be considered in the treatment of ATL. A phase II study reported long overall survival despite short progression-free survival in patients, implying that lenalidomide confers a survival benefit through immunomodulation for patients with ATL. We herein report that low-dose lenalidomide as maintenance therapy maintained a complete remission in a patient with aggressive ATL, whose condition has since remained stable with no recurrence for 24 months.
EPOCH regimen as salvage therapy for adult T-cell leukemia-lymphoma. [2018]Adult T-cell leukemia-lymphoma (ATL) is an intractable hematopoietic malignancy with a very poor prognosis. Although improved responses have been achieved through intensive chemotherapy in newly diagnosed patients with aggressive ATL, most patients suffer from relapse or disease recurrence, and an effective salvage therapy, especially for candidates for allogeneic hematopoietic stem cell transplantation (allo-HSCT), is yet to be established. The efficacy of the EPOCH regimen has been reported for several lymphoid malignancies; however, its efficacy for ATL has not been sufficiently evaluated. Here, we report results of a study of the EPOCH regimen as a salvage therapy for ATL. We retrospectively analyzed patients with relapsed or refractory ATL treated in our institution, with EPOCH as a first salvage therapy. Fourteen patients with a median age of 58 years were analyzed, among whom eight achieved a response, including a complete response in one patient and partial responses in seven. Seven patients underwent allo-HSCT after EPOCH therapy; however, the median overall survival (OS) could not be determined, whereas OS at 2 years after allo-HSCT was estimated to be 85.7%. These results suggest that EPOCH is an option for salvage therapy in patients with ATL, including candidates for allo-HSCT.
Diagnosis and management of adult T-cell leukemia/lymphoma. [2022]Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-cell leukemia virus type I (HTLV-1). Between 3% and 5% of HTLV-1-infected individuals develop ATL after a long latency. Confirmation of seropositivity of anti-HTLV-1 antibody, and clonal proliferation of CD4 and CD25 positive lymphocytes with nuclear pleomorphism in patients suspicious of malignant lymphoma or chronic lymphocytic leukemia is crucial for the diagnosis of ATL. The clinical course of ATL is very heterogeneous, and divided into acute, lymphoma, chronic, and smoldering types. The chronic type is further subclassified into the favorable and unfavorable subtypes. Acute, lymphoma, and unfavorable chronic type ATL, and favorable chronic and smoldering type ATL are defined as aggressive and indolent ATL, respectively. Recently identified prognostic indices based on clinical parameters and/or genetic predictors of outcomes need to be confirmed and incorporated for more stratified therapeutic interventions. The standard of care for aggressive ATL is multiagent chemotherapy followed by allogeneic hematopoietic stem cell transplantation if possible, while that for indolent ATL is watchful waiting until progression to aggressive ATL. The combination of interferon-α and zidovudine is also standard for leukemic type ATL. In addition, mogamulizumab, lenalidomide, and brentuximab vedotin have been incorporated into clinical practices in Japan. Furthermore, several novel drugs are currently undergoing clinical trials.