Mogamulizumab + DA-EPOCH for T-Cell Lymphoma
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Sethi
Must not be taking: Immunomodulatory drugs
Disqualifiers: Pregnancy, Active infection, CNS metastases, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?Single- arm Phase II study evaluating the combination of mogamulizumab (MOGA) added on top of standard of care dose adjusted EPOCH (DA-EPOCH) in patients with newly diagnosed or relapsed/refractory (for CTCL only) aggressive T cell lymphoma including patients with Adult T-cell leukemia/lymphoma (ATLL).
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, if you are on certain immunomodulatory drugs or have received them within 4 weeks of treatment, you may be excluded from participating. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the treatment Mogamulizumab + DA-EPOCH for T-Cell Lymphoma?
The DA-EPOCH treatment, which is part of the Mogamulizumab + DA-EPOCH therapy, has shown a high response rate and tolerable side effects in patients with peripheral T-cell lymphoma, with 78% of patients responding to the treatment and 61% achieving complete remission.
12345Is the combination of Mogamulizumab and DA-EPOCH safe for humans?
The DA-EPOCH regimen, used for aggressive lymphomas, has been studied and found to be generally safe, with common side effects including neutropenia (low white blood cell count) and infections. There were no treatment-related deaths reported in the studies, but some patients experienced severe infections. Mogamulizumab, another component of the treatment, has been used in other conditions, but specific safety data for its combination with DA-EPOCH in T-cell lymphoma is not provided in the available studies.
12567How is the treatment Mogamulizumab + DA-EPOCH for T-Cell Lymphoma different from other treatments?
Mogamulizumab + DA-EPOCH is unique because it combines a targeted therapy (mogamulizumab) with a dose-adjusted chemotherapy regimen (DA-EPOCH) to potentially improve outcomes for T-cell lymphoma, a condition with limited standard treatment options. This approach aims to enhance the effectiveness of chemotherapy by adjusting doses based on patient tolerance and adding a drug that specifically targets cancer cells.
148910Eligibility Criteria
Adults with confirmed aggressive T-cell Non-Hodgkin lymphoma, including various subtypes like PTCL and CTCL, can join this trial. They should have a decent performance status (able to carry out daily activities) and may have had one cycle of certain chemotherapies. Women must not be pregnant or breastfeeding and agree to use contraception; men also need to commit to using contraception.Inclusion Criteria
I have received specific chemotherapy for aggressive T cell lymphoma.
I am not pregnant or breastfeeding.
My organs and bone marrow are working well.
+5 more
Exclusion Criteria
I have not had cancer treatment recently.
I have recently undergone radiotherapy.
I am taking drugs that modify my immune system.
+14 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive Mogamulizumab and DA-EPOCH for 6 cycles, with Mogamulizumab administered on days 1, 8, 15 of the first cycle and day 1 of subsequent cycles, and DA-EPOCH on day 1 of each cycle
18 weeks
6 cycles (in-person visits for each cycle)
Follow-up
Participants are monitored for safety and effectiveness after treatment, including assessments for complete response and occurrence of toxicity
2 years
Extension/Long-term follow-up
Participants are monitored for progression-free survival, overall survival, and duration of response
2 years
Participant Groups
The study is testing the effectiveness of Mogamulizumab when added to the DA-EPOCH chemotherapy regimen in patients with newly diagnosed or relapsed/refractory aggressive T cell lymphoma. It's a Phase II trial where all participants receive this combination treatment.
1Treatment groups
Experimental Treatment
Group I: Mogamulizumab + DA-EPOCHExperimental Treatment2 Interventions
All subjects are scheduled to receive six cycles of DA-EPOCH + Mogamulizumab
Cycle 1: Mogamulizumab on days 1,8,15, of a 21-day cycle with DA-EPOCH on day 1.
Cycle 2 onwards: Mogamulizumab on day 1 with DA-EPOCH
Mogamulizumab will be administered modified to a 21-day cycle in combination with chemotherapy. Subjects will receive 1.0 mg/kg of mogamulizumab as an IV infusion over at least 1 hour on Days 1, 8, 15 of the first cycle and Day 1 for the subsequent cycles. This dosing regimen will ensure the first 4 doses are given weekly at a dose of 1 mg/kg. Subsequent dosing will occur on a 21-day schedule to coincide with the frequency of administration of DA-EPOCH to allow for simpler co-administration of the study drugs.
DA-EPOCH Protocol is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as DA-EPOCH for:
- Diffuse Large B-Cell Lymphoma (DLBCL)
- Primary Mediastinal Large B-Cell Lymphoma (PMBCL)
- Burkitt Lymphoma
- Aggressive Non-Hodgkin Lymphoma (NHL)
🇪🇺 Approved in European Union as DA-EPOCH for:
- Diffuse Large B-Cell Lymphoma (DLBCL)
- Primary Mediastinal Large B-Cell Lymphoma (PMBCL)
- Burkitt Lymphoma
- Aggressive Non-Hodgkin Lymphoma (NHL)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Yale Smilow Cancer HospitalNew Haven, CT
Yale Cancer Center, Clinical Trials OfficeNew Haven, CT
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Who Is Running the Clinical Trial?
SethiLead Sponsor
Yale UniversityLead Sponsor
Tarsheen SethiLead Sponsor
Kyowa Kirin, Inc.Industry Sponsor
References
Dose-adjusted EPOCH and rituximab (DA-EPOCH-R) in older patients with high-risk aggressive diffuse large B-cell lymphoma: A real-life multicenter study by the Croatian Cooperative Group for Hematologic diseases (KroHem). [2023]Dose-adjusted EPOCH and rituximab (DA-EPOCH-R) is a regimen used for the treatment of high-risk diffuse large B-cell lymphoma (DLBCL) designed to overcome resistance to standard R-CHOP by combining prolonged exposure of lymphoma cells to cytotoxic agents and dose-adjustment based on toxicity. Data on outcomes of older patients are scarce.
[Rituximab combined with EPOCH regimen for treatment of diffuse large B cell lymphoma of the gastrointestinal tract: analysis of 4 cases]. [2018]We treated 4 with a diagnosis of diffuse large B cell lymphoma involving the gastrointestinal tract with rituximab combined with adjusted dose EPOCH (R-DA-EPOCH) scheme based on a comprehensive analysis of the onset process, clinical and pathological features, and prognosis of the patients, and evaluated their treatment response. Complete remission (CR) was achieved in 3 patients after the treatment and 1 patient with diabetes and hypertension died due to severe infection. R-DA-EPOCH regimen as the first-line treatment of gastrointestinal diffuse large B cell lymphoma has a good short-term efficacy, but its long-term efficacy awaits further evaluation in future studies with larger sample sizes.
Pegylated GCSF Can Be Used With First-Line da-EPOCH-R Without Compromising Dose Intensity, Safety, or Efficacy. [2019]Infusional da-EPOCH-R (dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab) is a dose-intensified regimen with a potential role in treating high-risk subtypes of aggressive B-cell non-Hodgkin lymphoma (B-NHL). Studies of da-EPOCH-R use daily injections of granulocyte colony-stimulating factor (GCSF) to tailor chemotherapy dosing, and whether 1-time administration of pegylated GCSF (peg-GCSF) is as efficacious has not been addressed.
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.
Dose-adjusted EPOCH with or without rituximab for aggressive lymphoma patients: real world data. [2022]CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) -/+ rituximab (R) is the standard chemotherapeutic regimen for aggressive lymphoma, but is insufficient for aggressive lymphoma with adverse prognostic factors. Dose-adjusted (DA)-EPOCH (etoposide, doxorubicin, cyclophosphamide, vincristine, and prednisolone) -/+ R demonstrates excellent efficacy against some aggressive lymphoma. Thus, we conducted a retrospective study to evaluate the feasibility and efficacy of this therapy in clinical practice. We enrolled 149 patients from 17 institutions diagnosed between 2007 and 2015. The median follow-up period for survivors was 27 months (range 0.2-123). The complete response (CR) rate of newly diagnosed patients was 79% (95% CI 68-87%). All patients were hospitalized to receive this therapy and 94% of patients also received granulocyte-colony-stimulating factor support. There were no treatment-related deaths. Febrile neutropenia (FN) and grade 3 or 4 infection occurred in 55% and 28% of patients, respectively. There were no significant differences in FN or infection between young (≤ 65 years) and elderly patients (> 65 years). In newly diagnosed diffuse large B-cell lymphoma-not otherwise specified patients (n = 46), the CR rate was 80% (95% CI 64-91%) and the 2-year OS rate was 81% (95% CI 66-90%). In the present study, DA-EPOCH -/+ R exhibited excellent efficacy and feasibility for aggressive lymphoma.
Safety and financial analysis of outpatient dose-adjusted EPOCH for B-cell lymphoma at a tertiary comprehensive cancer center. [2021]Dose-adjusted (DA-) EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) is a front-line treatment option for aggressive B-cell lymphomas. Due to regimen complexity, inpatient administration of DA-EPOCH has been historically required. Moffitt Cancer Center (MCC) developed an Inpatient/Outpatient (IPOP) program to facilitate administration of complicated regimens in the outpatient setting. We hypothesized that outpatient administration of DA-EPOCH at a comprehensive cancer center is both safe and cost-effective.
Dose-adjusted EPOCH plus rituximab is an effective regimen in patients with poor-prognostic untreated diffuse large B-cell lymphoma: results from a prospective observational study. [2015]This study was designed to assess the efficacy and safety of an infusional DA-EPOCH (dose-adjusted etoposide/vincristine/doxorubicin/bolus cyclophosphamide/prednisone) and rituximab (DA-EPOCH-R) regimen for patients with poor prognosis diffuse large B-cell lymphoma (DLBCL). Thirty-three patients, aged 21-76 years, with an age-adjusted International Prognostic Index (IPI) of 2 or 3, were enrolled, and 31/33 patients were evaluable for response. Consolidative radiation therapy was given to eight patients with bulky (> or =10 cm) disease at presentation. Overall, 26 patients (83.8%) achieved a complete remission (CR), four patients (12.9%) achieved a partial remission, and one patient (3.2%) died during induction. Two patients relapsed (7.6%) within 15 months. Grade 3-4 neutropenia developed in 52% of cycles and neutropenic fever in 14% of cycles (51% of patients). The estimates for event-free survival (EFS) and overall survival at 2 years were 68% and 75% respectively. The only factor related to poor EFS was the presence of three age-adjusted IPI-risk factors. We conclude that DA-EPOCH-R has clinically significant activity with a favourable toxicity profile for poor-prognostic DLBCL patients. The administration of DA-EPOCH-R as an outpatient regimen by using a single portable infusion pump may be a feasible alternative to improve the compliance and to reduce the total cost of this very effective regimen.
Complications Associated With Dose-adjusted EPOCH-rituximab Therapy for Non-Hodgkin Lymphoma. [2019]Certain aggressive non-Hodgkin lymphoma subtypes are increasingly being treated with infusional DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab), which requires a central venous catheter. This study aims to identify the rates and predictors of line-associated complications (LACs) associated with DA-EPOCH-R therapy in NHL.
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]Alliance/CALGB 50303 (NCT00118209), an intergroup, phase III study, compared dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as frontline therapy for diffuse large B-cell lymphoma.
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.