Dose Adjusted EPOCH-R, to Treat Mature B Cell Malignancies
Dose Adjusted EPOCH-R, to Treat Mature B Cell Malignancies
The subject is invited to take part in this research study because s/he has been diagnosed
 with Diffuse Large B-Cell Lymphoma (DLBCL), Primary Mediastinal B-cell Lymphoma (PMBCL), or
 Post-transplant Lymphoproliferative Disorder (PTLD).

 In an attempt to improve cure rates while reducing harmful effects from drugs, oncologists
 are developing new treatment protocols. One such protocol, entitled dose-adjusted EPOCH-R,
 utilizes two major new strategies. First, the treatment approach utilizes continuous infusion
 of chemotherapy over four days, instead of being administered over minutes or hours.
 Secondly, the doses of some medications involved are increased or decreased based on how the
 drugs affect the subject's ability to produce blood cells, which is used as a measure of how
 rapidly the body is processing drugs.

 Using this approach in adults, researchers have shown improved cure rates in these cancers.
 Additionally, the harmful effects experienced by patients has been mild, with mucositis,
 severe infections, and tumor lysis syndrome occurring rarely. However, this new dosing method
 has never been used in children, and the effectiveness and side effects of this new method
 are unknown in children.

 The purpose of this study is to look at the safety of dose-adjusted EPOCH-R in the treatment
 of children with mature B-cell cancers, and to see if we can maintain cure rates (as has been
 shown in adults). This study represents the first trial of dose-adjusted EPOCH-R in children.
The subject will need to have a variety of tests, exams, or procedures to find out if s/he
 can be on the study.

 The subject will also require placement of a catheter that stays in the vein for safe
 administration of chemotherapy drugs.

 During the study...

 If all of the tests that have been done show that s/he can participate and s/he chooses to
 participate, treatment cycles will begin.

 A cycle equals three weeks. The subject will have a minimum of 6 cycles of treatment,
 possibly 8. The cancer drugs s/he will receive are etoposide, vincristine, doxorubicin,
 cyclophosphamide, prednisone, and rituximab with each cycle. The amount of the drugs will be
 determined by the subject's weight at first, and some of the drugs will be adjusted up or
 down for later cycles.

 Rituximab will be given on Day 1 prior to continuous infusion drugs.

 After 4 cycles, the subject will have imaging scans again to see how the cancer responded to
 treatment. If the cancer responds completely after 4 cycles, s/he will get 2 more cycles (6
 cycles total). If the cancer partially responds, s/he will get 4 more cycles (8 total
 cycles).

 If the subject has cancer in the Central Nervous System, s/he will receive a drug called
 methotrexate. If s/he does not have cancer in the CNS, s/he will get methotrexate to try to
 prevent CNS cancer.
Inclusion Criteria:

 -  Patient with newly diagnosed, histologically confirmed, Group B or C diffuse large
 B-cell lymphoma; or primary mediastinal B-cell lymphoma. Patients with Group B/C post
 transplant lymphoproliferative disorder are eligible for the study regardless of
 whether disease is newly diagnosed. (Murphy staging will be used for group
 classification.)

 Exclusion Criteria:

 -  Patient who has received previous chemotherapy or radiation therapy in the previous 3
 months, except for empiric initial intrathecal administration at diagnosis. Rituximab
 or steroid administration is not an exclusion criterion.

 -  Patient who has received any prior anthracyclines.

 -  Patient with symptomatic cardiac failure unrelieved by medical therapy or evidence of
 significant cardiac dysfunction by echocardiogram (shortening fraction <28%) NOT due
 to mediastinal mass.

 -  Patient with severe renal disease (i.e. creatinine greater than 3 times normal for
 age; creatinine clearance less than 50 ml/min/1.73m2).

 -  Patient with severe hepatic disease (direct bilirubin greater than 3 mg/dl or AST
 greater than 500 IU/L).

 -  Patient with a Karnofsky performance score <50% or Lansky score <50%.

 -  HIV-positive patients will be excluded unless antiretroviral therapy can be safely
 withheld during chemotherapy administration, based on clinical determination of
 infectious disease team evaluation.

 -  Female patient who is pregnant or breastfeeding.

 -  Patient with reproductive potential not willing to use an acceptable method of birth
 control (i.e. hormonal contraception, intrauterine device, condom or diaphragm with
 spermicide, or abstinence) for the duration of the study and one year post completion
 of therapy.

 -  Patient with primary central nervous system (CNS) lymphoma (lymphoma limited to the
 craniospinal axis without systemic involvement)

 -  Patient with Burkitt cell lymphoma or leukemia.

 -  Patient with group classification A disease, or group classification B stage I or II
 disease with normal LDH level AND tumor mass less than 7 cm.