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Burkitt LymphomaPhase 2NCT01092182

Phase II Study of Dose-Adjusted EPOCH-Rituximab in Adults With Untreated Burkitt Lymphoma and c-MYC+ Diffuse Large B-Cell Lymphoma

A Phase 2 study testing EPOCH-R and EPOCH-RR in people with Burkitt Lymphoma and Diffuse Large B-cell Lymphoma, c-MYC Positive, run by National Cancer Institute (NCI) at 30 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
EPOCH-R and EPOCH-RR
Could I receive a placebo?
No, everyone receives an active treatment
How many people
194 participants
Where
30 sitesUnited States
Study dates
25 Mar 2010to 16 Feb 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

30 sites in 1 country.

30 sites in 1 country

United States30 sites

  • Emory University /Winship Cancer Institute

    Atlanta, Georgia, 30322

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

  • Massachusetts General Hospital Cancer Centers

    Boston, Massachusetts, 02114

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts

  • University of Illinois

    Chicago, Illinois, 60607

  • Case Western Reserve University

    Cleveland, Ohio, 44106-2602

  • MetroHealth Medical Center

    Cleveland, Ohio, 44109

  • Cleveland Clinic

    Cleveland, Ohio

  • UT Southwestern /Simmons Cancer Center- Dallas

    Dallas, Texas, 75390

  • Fairview - Southdale Hospital

    Edina, Minnesota

  • Unity Hospital

    Fridley, Minnesota, 55432

  • MD Anderson Cancer Center

    Houston, Texas, 77030-4096

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007

  • Vidant Oncology-Kinston

    Kinston, North Carolina, 28501

  • University of Tennessee - Knoxville

    Knoxville, Tennessee, 37996

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

  • University of Kentucky /Markey Cancer Center

    Lexington, Kentucky, 40536

  • UCLA Center for Clinical AIDS Research and Education

    Los Angeles, California, 90025

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Froedtert and the Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Mount Sinai Hospital

    New York, New York, 10017

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 11570

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • University of Rochester

    Rochester, New York, 14627

  • Park Nicollet Clinic - Saint Louis Park

    Saint Louis Park, Minnesota, 55416

  • Washington University School of Medicine

    St Louis, Missouri

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: Phase II Study of Dose-Adjusted EPOCH+/-Rituximab in Adults With Untreated Burkitt Lymphoma, c-MYC Positive Diffuse Large B-Cell Lymphoma and Plasmablastic Lymphoma

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.
Read more

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.
Read the detailed description

Background:

  • Burkitt lymphoma/leukemia (BL) is highly curable. Standard treatment employs dose intense multi-agent chemotherapy and though effective is associated with high morbidity. Therefore, novel approaches are needed that improve the therapeutic index of BL while maintaining or improving efficacy. In human immunodeficiency virus (HIV)+ BL, outcome has been poor, mainly due to the use of cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate (Oncovin), and prednisone (CHOP) based regimens in this disease.
  • Two National Cancer Institute (NCI) phase II trials have used etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) chemotherapy with 1 or 2 doses of rituximab (R) per cycle in untreated BL. (Dose-adjusted) etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH)-Rituximab has been used in16 HIV negative BL, and 8 HIV positive patients have received 3 to 4 cycles of EPOCHRR to minimize toxicity and risk of opportunistic infections. All patients remain in continuous remission. Treatment was very well tolerated and represents a novel therapeutic strategy in BL.
  • This trial seeks to assess the effectiveness of a risk adaptive approach with DA-EPOCHR in untreated BL (HIV+/-). Because this treatment represents a major conceptual departure from standard treatment, it is important to obtain additional Phase II results in limited/advanced stage BL
  • c-MYC positive Diffuse large B cell (DLBCL) is a rare variant of Diffuse Large B-Cell Lymphoma (DLBCL). There is very little data on the biology of this disease and what the optimal therapeutic approach should be has not been defined. Therefore, based on our impression that this behaves aggressively and is likely characterized by a high tumor proliferation rate, we plan to accrue patients with this disease in addition to BL patients.
  • Plasmablastic lymphoma, another variant of DLBCL is frequently characterized by the activation of MYC and has had a poor outcome historically with standard treatment. We plan to include these patients in the study also. As they are cluster of differentiation 20 (CD20) negative, they will receive DA-EPOCH without Rituximab.

Objectives:

  • Determine progression free survival (PFS), event free survival (EFS) and overall survival (OS) of risk adaptive DA-EPOCH-R in untreated BL and c-MYC + DLBCL and DA-EPOCH in c-MYC+ plasmablastic lymphoma.
  • Assess predictive value of early fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) scans on PFS.
  • Obtain pilot comparative molecular profiling in HIV negative and positive BL and c- MYC + DLBCL, including c-MYC+ plasmablastic lymphoma.

Eligibility:

  • Burkitt lymphoma, c-MYC + DLBCL and c-MYC + plasmablastic lymphoma age greater than or equal to 18 years.
  • No prior treatment except limited-field radiotherapy, short course of glucocorticoids and/or cyclophosphamide for an urgent problem at diagnosis.
  • Adequate major organ function unless impairment due to lymphoma.

Study Design:

  • Phase II Study of risk adapted DA-EPOCH-R in BL, c-MYC + DLBCL and DA-EPOCH in c-MYC+ plasmablastic lymphoma
  • Low risk: DA-EPOCH-RR x 3 cycles.
  • High risk , c-MYC + DLBCL and c-MYC+ plasmablastic lymphoma : DA-EPOCH (+/-) R x 6 cycles or 8 cycles in select patients.
  • Cerebrospinal fluid (CSF) cytology and flow cytometry for analysis of BL.
  • High Risk CSF negative - Prophylactic intrathecal treatment
  • CSF positive - Active intrathecal treatment
  • FDG-PET/CT pre- and post-cycle 2 in all patients.
  • A total of 194 patients will be enrolled in the protocol.
Being tested
EPOCH-R, EPOCH-RR
Keywords
Microarray, Toxicity, Therapeutic Index, HIV Positive, HIV Negative, HIV Infections
Medical subject headings
Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Plasmablastic Lymphoma, HIV Seropositivity, HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EPOCH-RDrug

    Also called Etoposide, Prednisone, Vincristine, Cyclophosphamide

    Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles

  • EPOCH-RRDrug

    Also called Etoposide, Prednisone, Vincristine, Cyclophosphamide

    Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 3 cycles

Study groups in NCT01092182
Study groupRoleWhat they receive
Group A - Burkitt lymphoma Low Risk ArmExperimentalBurkitt lymphoma Low Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles
Receives: Drug: EPOCH-RR
Group B - Burkitt lymphoma High Risk ArmExperimentalBurkitt lymphoma High Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles
Receives: Drug: EPOCH-R
Group C - DLBCL high risk armExperimentalDiffuse large B-cell lymphoma (DLBCL) high risk arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles
Receives: Drug: EPOCH-R

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Time of progression or death at 4 years

  2. 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.

    Measured: At 4 years

  3. 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.

    Measured: At 4 years

Secondary outcomes (1)

  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

    The predictive value of early FDG-PET/CT scans on PFS was assessed after cycle 2. PFS is the time interval from start of treatment to documented evidence of disease progression, assessed 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.

    Measured: After 2 cycles of therapy and prior to cycle 3

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Mar 2010 (estimated)
  2. Study start25 Mar 2010
  3. Primary completion30 Sep 2020
  4. Study completion16 Feb 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
194 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01092182
Sponsor's protocol ID
100052
Other IDs
10-C-0052
Status last verified
Apr 2023
First submitted
23 Mar 2010
Last updated
27 Apr 2023
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 32453640

  • Dunleavy 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.

    PubMed 30501868

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing EPOCH-R and EPOCH-RR in people with Burkitt Lymphoma and Diffuse Large B-cell Lymphoma, c-MYC Positive, run by National Cancer Institute (NCI) at 30 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 30 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Kaplan-Meier Curve Progression Free Survival (PFS) Constructed With an 95% Confidence Interval (time frame: Time of progression or death at 4 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01092182, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2023.

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