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

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ClinicalTrials.gov Identifier: NCT01092182
Recruitment Status : Active, not recruiting
First Posted : March 24, 2010
Results First Posted : October 19, 2021
Last Update Posted : November 3, 2021
Sponsor:
Information provided by (Responsible Party):
Mark Roschewski, M.D., National Cancer Institute (NCI)

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.

Condition or disease Intervention/treatment Phase
Burkitt Lymphoma Diffuse Large B-cell Lymphoma, c-MYC Positive Plasmablastic Lymphoma Drug: EPOCH-R Drug: EPOCH-RR Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 194 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 25, 2010
Actual Primary Completion Date : September 30, 2020
Estimated Study Completion Date : February 28, 2023


Arm Intervention/treatment
Experimental: Group A - Burkitt lymphoma Low Risk Arm
Burkitt lymphoma Low Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles
Drug: EPOCH-RR
Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 3 cycles
Other Names:
  • Etoposide
  • Prednisone
  • Vincristine
  • Cyclophosphamide
  • Doxorubicin
  • Rituximab

Experimental: Group B - Burkitt lymphoma High Risk Arm
Burkitt lymphoma High Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles
Drug: EPOCH-R
Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles
Other Names:
  • Etoposide
  • Prednisone
  • Vincristine
  • Cyclophosphamide
  • Doxorubicin
  • Rituximab

Experimental: Group C - DLBCL high risk arm
Diffuse large B-cell lymphoma (DLBCL) high risk arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles
Drug: EPOCH-R
Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles
Other Names:
  • Etoposide
  • Prednisone
  • Vincristine
  • Cyclophosphamide
  • Doxorubicin
  • Rituximab




Primary Outcome Measures :
  1. 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 ]
    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.

  2. Percentage of Participants With Kaplan-Meier Curve Event Free Survival (EFS) Constructed With an 95% Confidence Interval [ Time Frame: At 4 years ]
    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.

  3. Percentage of Participants Kaplan-Meier Curve Overall Survival (OS) Constructed With an 95% Confidence Interval [ Time Frame: At 4 years ]
    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.


Secondary Outcome Measures :
  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 [ Time Frame: After 2 cycles of therapy and prior to cycle 3 ]
    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.


Other Outcome Measures:
  1. Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) [ Time Frame: 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. ]
    Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

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.

EXCLUSION CRITERIA:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01092182


Locations
Show Show 30 study locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Mark J Roschewski, M.D. National Cancer Institute (NCI)
  Study Documents (Full-Text)

Documents provided by Mark Roschewski, M.D., National Cancer Institute (NCI):
Informed Consent Form  [PDF] December 3, 2019

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Mark Roschewski, M.D., Principal Investigator, National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01092182    
Other Study ID Numbers: 100052
10-C-0052
First Posted: March 24, 2010    Key Record Dates
Results First Posted: October 19, 2021
Last Update Posted: November 3, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Mark Roschewski, M.D., National Cancer Institute (NCI):
Microarray
Toxicity
Therapeutic Index
HIV Positive
HIV Negative
HIV Infections
Additional relevant MeSH terms:
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Burkitt Lymphoma
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Plasmablastic Lymphoma
Lymphoma, Large-Cell, Immunoblastic
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Infections
Tumor Virus Infections
Prednisone
Cyclophosphamide
Rituximab
Doxorubicin
Liposomal doxorubicin
Etoposide
Etoposide phosphate
Vincristine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs