Phase II Study of Dose-Adjusted EPOCH-Rituximab in Adults With Untreated Burkitt Lymphoma and c-MYC+ Diffuse Large B-Cell Lymphoma
Condition: Burkitt Lymphoma; Diffuse Large B-cell Lymphoma, c-MYC Positive; Plasmablastic Lymphoma
MeSH terms: Burkitt Lymphoma; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Plasmablastic Lymphoma; Lymphoma, Large-Cell, Immunoblastic
Intervention: EPOCH-R; EPOCH-RR
Intervention description: 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
Intervention MeSH terms: Prednisone; Cyclophosphamide; Rituximab; Doxorubicin; Liposomal doxorubicin; Etoposide; Etoposide phosphate; Vincristine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 194.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Microarray; Toxicity; Therapeutic Index; HIV Positive; HIV Negative; HIV Infections

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.
    

Eligibility 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.