Dose Adjusted EPOCH-R, to Treat Mature B Cell Malignancies

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.

Conditions

• Diffuse Large B Cell Lymphoma
• Post Transplant Lymphoproliferative Disorder
• Primary Mediastinal (Thymic) Large B-cell Lymphoma

Interventions

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.

DRUG

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: * 2+ extranodal sites * elevated LDH, * MYC rearrangement OR * bone or marrow disease. ALL OTHERS receive IT MTX cycles 3-6.

DRUG

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.

DRUG

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.

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).

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.

DRUG

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.

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.

DRUG

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.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• Baylor College of Medicine

  lead OTHER

Principal Investigators

• Carl Allen, MD · Baylor College of Medicine

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Max Age

30 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-01-31

Primary Completion

2016-08-26

Completion

2016-12-31

FDA Drug

Yes

Countries

• United States

Study Locations