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

February 20, 2024 updated by: Carl Allen, Baylor College of Medicine

Use of Dose Adjusted EPOCH-R in the Treatment of Childhood 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

4

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • Texas Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • DA-EPOCH-R
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.

Other Names:
  • MTX
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.
Other Names:
  • VP-16
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.
Other Names:
  • Adriamycin
  • hydroxydaunorubicin
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:
  • VCR
  • Oncovin
  • LCR
  • Vincasar Pfs
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 Names:
  • Rituxan
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.
Other Names:
  • Cytoxan
  • CTX
  • Neosar
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 Names:
  • Deltasone
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.
Other Names:
  • Neupogen
  • Granulocyte - Colony Stimulating Factor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measure and assess adverse events
Time Frame: 1 year
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measure and assess immune function
Time Frame: 1 year
Blood will be taken to identify tumor and plasma biomarkers and mutations in patients with mature B-cell malignancies (DLBCL, PMBCL, and PTLD) that correlate with disease response and outcome using this novel therapeutic approach.
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Baylor College of Medicine

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Carl Allen, MD, Baylor College of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2013

Primary Completion (Actual)

August 26, 2016

Study Completion (Actual)

December 1, 2016

Study Registration Dates

First Submitted

December 17, 2012

First Submitted That Met QC Criteria

January 2, 2013

First Posted (Estimated)

January 4, 2013

Study Record Updates

Last Update Posted (Estimated)

February 21, 2024

Last Update Submitted That Met QC Criteria

February 20, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-30759, DA-EPOCH-R
  • DA-EPOCH-R (Other Identifier: BCM)
  • 5K12CA090433-12 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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