Dose Adjusted EPOCH-R, to Treat Mature B Cell Malignancies (DA-EPOCH-R)
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.
Diffuse Large B Cell Lymphoma
Post Transplant Lymphoproliferative Disorder
Primary Mediastinal (Thymic) Large B-cell Lymphoma
Drug: DA-EPOCH-R for DLBCL, PTLD, AND PMBCL
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Use of Dose Adjusted EPOCH-R in the Treatment of Childhood Mature B Cell Malignancies|
- Measure and assess adverse events [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]Adverse event data will be collected to evaluate the safety and feasibility of dose-adjusted EPOCH-R in the treatment of children with mature B-cell malignancies.
- Measure and assess immune function [ Time Frame: 1 year ] [ Designated as safety issue: No ]Blood will be taken to identify tumor and plasma biomarkers and mutations in patients with mature B-cell malignancies that correlate with disease response and outcome using this novel therapeutic approach.
|Study Start Date:||January 2013|
|Estimated Study Completion Date:||January 2026|
|Estimated Primary Completion Date:||January 2017 (Final data collection date for primary outcome measure)|
Experimental: DA-EPOCH-R for DLBCL, PTLD & PMBCL
Minimum 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.
Drug: DA-EPOCH-R for DLBCL, PTLD, AND PMBCL
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.
Other Name: DA-EPOCH-RDrug: Methotrexate
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:
ALL OTHERS receive IT MTX cycles 3-6.
Other Name: MTXDrug: Etoposide
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.
Other Name: VP-16Drug: Doxorubicin
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.
Other Names:Drug: Vincristine
Vincristine will be given on days 1-4 of each cycle at 0.4mg/m2/day (dose based on patient height and weight).
Other Names:Drug: Rituximab
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.
Other Name: RituxanDrug: Cyclophosphamide
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.
Other Names:Drug: Prednisone
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.
Other Name: DeltasoneDrug: G-CSF
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01760226
|Contact: Carl Allen, MDemail@example.com|
|Contact: Munu Bilgifirstname.lastname@example.org|
|United States, Texas|
|Texas Children's Hospital||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Carl Allen, MD 832-826-0860 email@example.com|
|Contact: Munu Bilgi 832-824-1518 firstname.lastname@example.org|
|Principal Investigator:||Carl Allen, MD||Baylor College of Medicine|