Phase II Study of Dose-Adjusted EPOCH-Rituximab in Adults With Untreated Burkitt Lymphoma and c-MYC+ Diffuse Large B-Cell Lymphoma
2 other identifiers
interventional
194
1 country
30
Brief Summary
Background:
- Burkitt lymphoma/leukemia (BL) is highly treatable, but most of the standard therapies require multiple doses of intensive chemotherapy that may require long hospital stays and frequently have severe side effects. In addition, BL is a fairly common type of cancer in patients who also have human immunodeficiency virus (HIV), but treatment outcomes are poor because standard treatments do not work very well in HIV-positive patients and the more intense treatment regimens are highly toxic. New approaches are needed that expand the ways to treat BL with the same efficiency but with reduced side effects.
- Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) is a standard chemotherapy treatment that consists of the drugs etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab. It may be able to treat BL with similar effectiveness but with fewer side effects. Researchers are interested in confirming the results of previous studies that investigated the effectiveness of DA-EPOCH-R in treating BL. Objectives: \- To determine the safety and effectiveness of DA-EPOCH-R in treating Burkitt lymphoma. Eligibility: \- Individuals at least 18 years of age who have been diagnosed with Burkitt lymphoma and have not had any prior chemotherapy treatments. Design:
- Individuals will have a series of blood and other tests to determine their suitability for participating in the study. Eligible participants will be divided into high-risk and low-risk groups based on their disease prognosis and the possibility that the BL may or already has spread into the central nervous system.
- Participants will receive intravenous infusion of the six chemotherapy drugs in DA-EPOCH-R in 21-day treatment cycles. The exact doses will be adjusted depending on participants white blood cell counts and other tests.
- High-risk participants will receive six cycles of DA-EPOCH-R. To treat BL that may have entered the central nervous system, high-risk participants will also receive infusions of other chemotherapy drugs into their spinal fluid.
- Low-risk participants will receive up to six cycles of DA-EPOCH-R, with an additional dose of rituximab during each cycle.
- Frequent blood and urine tests will be performed during treatment, as well as body imaging scans and other tests of cancer progression as directed by the study doctors. Participants will receive additional medicines to help prevent possible adverse side effects of DA-EPOCH-R.
- Participants who respond successfully to the treatment will be asked to return for follow-up exams every 3 months for the first 18 months, then every year for the next 3 years. Participants who do not respond successfully to the treatment will be given the opportunity to participate in additional research and treatment protocols, if any are available.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Mar 2010
Longer than P75 for phase_2
30 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 23, 2010
CompletedFirst Posted
Study publicly available on registry
March 24, 2010
CompletedStudy Start
First participant enrolled
March 25, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 30, 2020
CompletedResults Posted
Study results publicly available
October 19, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
February 16, 2023
CompletedApril 27, 2023
April 1, 2023
10.5 years
March 23, 2010
September 29, 2021
April 5, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Percentage of Participants With Kaplan-Meier Curve Progression Free Survival (PFS) Constructed With an 95% Confidence Interval
PFS is the time interval from start of treatment to documented evidence of disease progression. Disease progression was measured by the International Workshop Criteria (IWC). Progression is a positive positron emission tomography (PET) finding corresponding to the computed tomography (CT) abnormality (new lesion, increasing size of previous lesion), or a negative PET and a CT abnormality (new lesion, increasing size of previous lesion) of \< 1.5 cm (\< 1.0 cm in the lungs). Kaplan-Meier curves were constructed with an 95% confidence interval.
Time of progression or death at 4 years
Percentage of Participants With Kaplan-Meier Curve Event Free Survival (EFS) Constructed With an 95% Confidence Interval
EFS was determined from the date of enrolment in the study until the date of progression, last documentation of disease at or after the last treatment cycle, death, or last follow-up (whichever occurred first). Disease progression was measured by the International Workshop Criteria (IWC). Progression is a positive positron emission tomography (PET) finding corresponding to the computed tomography (CT) abnormality (new lesion, increasing size of previous lesion), or a negative PET and a CT abnormality (new lesion, increasing size of previous lesion) of \< 1.5 cm (\< 1.0 cm in the lungs). Kaplan-Meier curves were constructed with an 95% confidence interval.
At 4 years
Percentage of Participants Kaplan-Meier Curve Overall Survival (OS) Constructed With an 95% Confidence Interval
OS was calculated from the enrolment date until date of death or last follow-up using the Kaplan Meier. Kaplan-Meier curves were constructed with an 95% confidence interval.
At 4 years
Secondary Outcomes (1)
Kaplan-Meier Progression Free Survival (PFS) Constructed With an 95% Confidence Interval in Participants Who Underwent Fluorodeoxyglucose (FDG)-Positron Emission Tomography (PET) and/or Computed Tomography (CT) Scans After Cycle 2
After 2 cycles of therapy and prior to cycle 3
Other Outcomes (1)
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)
Date treatment consent signed to date off study, approximately 102 months and 25 days for Group A, 125 months and 28 days for Group B and 117 months and 29 days for group C.
Study Arms (3)
Group A - Burkitt lymphoma Low Risk Arm
EXPERIMENTALBurkitt lymphoma Low Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles
Group B - Burkitt lymphoma High Risk Arm
EXPERIMENTALBurkitt lymphoma High Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles
Group C - DLBCL high risk arm
EXPERIMENTALDiffuse large B-cell lymphoma (DLBCL) high risk arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles
Interventions
Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles
Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 3 cycles
Eligibility Criteria
You may qualify if:
- Patients must have one of the following histologic diagnoses:
- Patients must have Burkitt Lymphoma. Effective with Amendment J (version date: 06/24/2014), the following histologies were removed as the maximum number allowed for these sub-groups has been reached: B-cell lymphoma: unclassifiable with features intermediate between Diffuse Large B cell lymphoma and Burkitt Lymphoma ; c-MYC + Diffuse large B-cell lymphoma (DLBCL) and c-MYC+ plasmablastic lymphoma.
- If questions arise related to diagnosis, please contact the National Cancer Institute (NCI) Principal Investigator, Dr. Mark Roschewski or the NCI study coordinator, A. Nicole Lucas.
- Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) in patients \<18 years of age, children are excluded from this study, but may be eligible for future pediatric trials
- Pathology confirmed by treating institutions Pathology Department.
- No prior treatment except patients may be entered if they have had prior limited-field radiotherapy, a short course of glucocorticoids, cyclophosphamide for an urgent problem at diagnosis (e.g. epidural cord compression, superior vena cava syndrome) and/or a single dose of intrathecal methotrexate (MTX) at the time of the pre-treatment diagnostic lumbar puncture.
- All disease stages.
- Human immunodeficiency virus (HIV) negative or positive.
- HIV positive patients on antiretroviral therapy regimen must be willing to suspend all Highly Active Antiretroviral Therapy (HAART) except in circumstances described in section 6.5.
- Eastern Cooperative Oncology Group (ECOG) 0-4
- Ability of patient or durable power of attorney (DPA) for healthcare to give informed consent.
- Hepatitis B + patients may be enrolled at the discretion of the investigator.
You may not qualify if:
- Patients with Primary central nervous system (CNS) Lymphoma.
- Inadequate renal function, defined as serum creatinine (Cr) \> 1.5 or creatinine clearance \< 50ml/min/1.73m\^2 unless lymphoma related.
- Inadequate hepatic or hematological function: as follows, unless lymphoma-/disease-related: bilirubin greater than 2 mg/dl (total) except greater than 5 mg/dl in patients with Gilbert's syndrome as defined by greater than 80% unconjugated, absolute neutrophil count (ANC) less than 1000 and platelets less than 75,000.
- The effects of EPOCH-R on the developing human fetus are unknown. For this reason and because chemotherapy agents are known to be teratogenic, female subject of child-bearing potential not willing to use an acceptable method of birth control(i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study and one year beyond treatment completion will not be eligible to participate in the study.
- Female subject pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-human chorionic gonadotropin (hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for women without child-bearing potential.
- The effects of EPOCH-R on the developing human fetus are unknown. For this reason and because chemotherapy agents are known to be teratogenic, male subject unwilling to use an acceptable method for contraception for the duration of the study and one year beyond treatment completion, will not be eligible to participate in the study.
- History of a prior invasive malignancy in past 5 years.
- Active symptomatic ischemic heart disease, myocardial infarction or congestive heart failure within the past year. If echo is obtained the left ventricular ejection fraction (LVEF) should exceed 40%.
- Serious concomitant medical illnesses that would jeopardize the patient's ability to receive the regimen with reasonable safety.
- HIV positive patients with advanced immune suppression and evidence of HIV resistant to all combinations of antiretroviral therapy considered at high risk of non lymphoma related death within 12-months due to other acquired immunodeficiency syndrome (AIDS) complications should not be enrolled on the study.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (30)
UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
UCLA Center for Clinical AIDS Research and Education
Los Angeles, California, 90025, United States
Emory University /Winship Cancer Institute
Atlanta, Georgia, 30322, United States
University of Illinois
Chicago, Illinois, 60607, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242, United States
University of Kentucky /Markey Cancer Center
Lexington, Kentucky, 40536, United States
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892, United States
Massachusetts General Hospital Cancer Centers
Boston, Massachusetts, 02114, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02115, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
West Michigan Cancer Center
Kalamazoo, Michigan, 49007, United States
Fairview - Southdale Hospital
Edina, Minnesota, United States
Unity Hospital
Fridley, Minnesota, 55432, United States
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, 55416, United States
Washington University School of Medicine
St Louis, Missouri, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Mount Sinai Hospital
New York, New York, 10017, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 11570, United States
University of Rochester
Rochester, New York, 14627, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
Vidant Oncology-Kinston
Kinston, North Carolina, 28501, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
Case Western Reserve University
Cleveland, Ohio, 44106-2602, United States
MetroHealth Medical Center
Cleveland, Ohio, 44109, United States
Cleveland Clinic
Cleveland, Ohio, United States
University of Tennessee - Knoxville
Knoxville, Tennessee, 37996, United States
UT Southwestern /Simmons Cancer Center- Dallas
Dallas, Texas, 75390, United States
MD Anderson Cancer Center
Houston, Texas, 77030-4096, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792, United States
Froedtert and the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Related Publications (2)
Roschewski M, Dunleavy K, Abramson JS, Powell BL, Link BK, Patel P, Bierman PJ, Jagadeesh D, Mitsuyasu RT, Peace D, Watson PR, Hanna WT, Melani C, Lucas AN, Steinberg SM, Pittaluga S, Jaffe ES, Friedberg JW, Kahl BS, Little RF, Bartlett NL, Fanale MA, Noy A, Wilson WH. Multicenter Study of Risk-Adapted Therapy With Dose-Adjusted EPOCH-R in Adults With Untreated Burkitt Lymphoma. J Clin Oncol. 2020 Aug 1;38(22):2519-2529. doi: 10.1200/JCO.20.00303. Epub 2020 May 26.
PMID: 32453640DERIVEDDunleavy K, Fanale MA, Abramson JS, Noy A, Caimi PF, Pittaluga S, Parekh S, Lacasce A, Hayslip JW, Jagadeesh D, Nagpal S, Lechowicz MJ, Gaur R, Lucas A, Melani C, Roschewski M, Steinberg SM, Jaffe ES, Kahl B, Friedberg JW, Little RF, Bartlett NL, Wilson WH. Dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) in untreated aggressive diffuse large B-cell lymphoma with MYC rearrangement: a prospective, multicentre, single-arm phase 2 study. Lancet Haematol. 2018 Dec;5(12):e609-e617. doi: 10.1016/S2352-3026(18)30177-7.
PMID: 30501868DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Mark J. Roschewski
- Organization
- National Cancer Institute
Study Officials
- PRINCIPAL INVESTIGATOR
Mark J Roschewski, M.D.
National Cancer Institute (NCI)
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
March 23, 2010
First Posted
March 24, 2010
Study Start
March 25, 2010
Primary Completion
September 30, 2020
Study Completion
February 16, 2023
Last Updated
April 27, 2023
Results First Posted
October 19, 2021
Record last verified: 2023-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Clinical data available during the study and indefinitely.
- Access Criteria
- Clinical data will be made available upon request to the study principal investigator.
All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. All collected IPD will be shared with collaborators under the terms of collaborative agreements.