Dose Adjusted EPOCH-R, to Treat Mature B Cell Malignancies
DA-EPOCH-R
Use of Dose Adjusted EPOCH-R in the Treatment of Childhood Mature B Cell Malignancies
3 other identifiers
interventional
4
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for early_phase_1
Started Jan 2013
Longer than P75 for early_phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 17, 2012
CompletedStudy Start
First participant enrolled
January 1, 2013
CompletedFirst Posted
Study publicly available on registry
January 4, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 26, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2016
CompletedOctober 14, 2025
February 1, 2024
3.7 years
December 17, 2012
October 10, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Measure and assess adverse events
To evaluate the safety and feasibility of dose-adjusted EPOCH-R in the treatment of use in children and young adults with mature B-cell malignancies, including, DLBCL, and PMBCL, as well as in patients with post-transplant lymphoproliferative disorder (PTLD).
1 year
Secondary Outcomes (1)
Measure and assess immune function
1 year
Study Arms (1)
DA-EPOCH-R for DLBCL, PTLD & PMBCL
EXPERIMENTALMinimum of 6 cycles (cycle=3 weeks), possibly 8. Dosages of the drugs will be determined by the subject's weight and height for cycle 1. Thereafter, the dosages of some drugs will be adjusted up or down for the next cycle, dependent on the blood tests results. DA-EPOCH-R for 2 cycles then two more cycles of DA-EPOCH-R. If complete response (CR), then DA-EPOCH-R for more 2 cycles. If no CR, DA-EPOCH-R for 4 more cycles.
Interventions
Day 1: Rituximab IV Days 1-4: After rituximab, etoposide, vincristine, and doxorubicin will be given in a vein over 96 hours as a continuous infusion. Day 5: cyclophosphamide will be given in a vein Days 1-5: prednisone given by mouth twice a day G-CSF 5mcg/kg/day will be given under the skin from day 6 until ANC has improved.
CNS negative patients with high CNS risk DLBCL will receive age based, intrathecal dosing of MTX on days 1 and 5 of cycles 3 - 6 only. CNS positive patients will receive age based, intrathecal (within the spinal fluid) MTX twice weekly for 2 weeks past the first negative cytology with a minimum of 4 weeks treatment. Then, weekly for 6 weeks and then every 4 weeks for 6 months. DLBCL/PTLD/PMBCL CNS prophylaxis for cycles 3-6 ONLY if: * 2+ extranodal sites * elevated LDH, * MYC rearrangement OR * bone or marrow disease. ALL OTHERS receive IT MTX cycles 3-6.
Etoposide will be given at 50mg/m2/day on days 1-4 of the first cycle of therapy (dose based on patient height and weight). The doses in later cycles will be adjusted up or down based on the patient's blood test results.
Doxorubicin will be given at 10mg/m2/day on days 1-4 of the first cycle (dose based on patient height and weight). The doses in later cycles will be adjusted up or down based on the patient's blood test results.
Vincristine will be given on days 1-4 of each cycle at 0.4mg/m2/day (dose based on patient height and weight).
Rituximab (375mg/m2/dose) will only be given on Day 1 of each cycle prior to all the other chemotherapy agents. Dose is based on patient height and weight.
Cyclophosphamide will be given on Day 5 of each cycle. In cycle 1, the dose will be 750 mg/m2 (based on patient height and weight), and the dose will be adjusted up or down for future cycles based on blood test results.
Prednisone will be given by mouth at 60mg/m2/dose (based on height and weight) twice a day on days 1-5 of each cycle.
G-CSF will be given at 5 mcg/kg/day during each cycle, starting on day 6, until the patient's ANC (absolute neutrophil count) is greater than 5000/mcL past nadir.
Eligibility Criteria
You may qualify if:
- Patient with newly diagnosed, histologically confirmed, diffuse large B-cell lymphoma, or primary mediastinal B-cell lymphoma; or patient has post-transplant lymphoproliferative disorder regardless of when diagnosed.
You may not qualify if:
- Patient has received previous chemotherapy or radiation therapy in the three months prior to therapy, except for empiric initial intrathecal administration at diagnosis
- 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%.
- Patient has been documented HIV positive and is unwilling/unable to stop antiretroviral therapy
- Female patient who is pregnant or breastfeeding.
- Patient is of reproductive potential and is not willing to use an acceptable method of birth control
- Patient has group classification A at diagnosis (completely resected stage I or completely resected stage II abdominal lesions)
- Patient has group classification B stage I or II disease with normal LDH level AND tumor mass less than 7 cm
- Patient has primary CNS lymphoma (lymphoma limited to the craniospinal axis without systemic involvement)
- Patient has Burkitt lymphoma or leukemia
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Baylor College of Medicinelead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
Texas Children's Hospital
Houston, Texas, 77030, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Carl Allen, MD
Baylor College of Medicine
Study Design
- Study Type
- interventional
- Phase
- early phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Associate Professor
Study Record Dates
First Submitted
December 17, 2012
First Posted
January 4, 2013
Study Start
January 1, 2013
Primary Completion
August 26, 2016
Study Completion
December 1, 2016
Last Updated
October 14, 2025
Record last verified: 2024-02