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

This study is currently recruiting participants.
Verified October 2013 by Baylor College of Medicine
Sponsor:
Collaborators:
Texas Children's Hospital
Information provided by (Responsible Party):
Stephen Simko, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT01760226
First received: December 17, 2012
Last updated: October 22, 2013
Last verified: October 2013
  Purpose

The subject is invited to take part in this research study because s/he has been diagnosed with Burkitt lymphoma and/or leukemia, 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.


Condition Intervention
Burkitt Lymphoma
Burkitt Leukemia
Diffuse Large B Cell Lymphoma
Post Transplant Lymphoproliferative Disorder
Primary Mediastinal (Thymic) Large B-cell Lymphoma
Drug: DA-EPOCH-R for BL and B-ALL
Drug: Methotrexate
Drug: Etoposide
Drug: Doxorubicin
Drug: Vincristine
Drug: Rituximab
Drug: Cyclophosphamide
Drug: Prednisone
Drug: G-CSF
Drug: DA-EPOCH-R for DLBCL, PTLD & PMBCL

Study Type: Interventional
Study Design: Allocation: Non-Randomized
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

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 12
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)
Arms Assigned Interventions
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: Methotrexate

CNS negative patients with Burkitt's lymphoma and 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 Name: 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 Name: 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:
  • Oncovin
  • LCR
  • VCR
  • 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 Name: 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
  • Neosar
  • CTX
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: 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
Drug: DA-EPOCH-R for DLBCL, PTLD & 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-R
Experimental: DA-EPOCH-R for BL and B-ALL

Minimum of 6 cycles (cycle=3 weeks). Dosages of the drugs will be determined by the subject's weight and height for cycle 1. Thereafter, some of the dosages will be adjusted up or down for the next cycle, dependent on the blood tests results.

DA-EPOCH-R for 2 cycles then DA-EPOCH-R for 4 cycles plus CNS prophylaxis.

Drug: DA-EPOCH-R for BL and B-ALL

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 Burkitt's lymphoma and 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 Name: 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 Name: 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:
  • Oncovin
  • LCR
  • VCR
  • 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 Name: 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
  • Neosar
  • CTX
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: 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

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.

For patients with Burkitt Lymphoma and B-ALL:

A cycle equals three weeks. The subject will have a minimum of 6 cycles of treatment. 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.

After two cycles of treatment, the subject will have imaging scans to see how the cancer responded to treatment. If the cancer responded partially or completely to treatment, s/he will receive an additional four cycles of treatment that are dose-adjusted like before.

For subjects with DLBCL, PTLD, and PMBCL:

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).

For all subjects:

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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient with newly diagnosed, histologically confirmed, Group B or C Burkitt lymphoma or leukemia (acute lymphoblastic leukemia, L3 subtype); 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 group classification A disease, or group classification B stage I or II disease with normal LDH level AND tumor mass less than 7 cm.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01760226

Contacts
Contact: Stephen Simko, MD 832-824-4848 sjsimko@txch.org
Contact: Susan Pilat, RN 832-824-1520 srpilat@txch.org

Locations
United States, Texas
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Stephen Simko, MD    832-824-4848    sjsimko@txch.org   
Sponsors and Collaborators
Baylor College of Medicine
Texas Children's Hospital
Investigators
Principal Investigator: Stephen Simko, MD Baylor College of Medicine
  More Information

No publications provided

Responsible Party: Stephen Simko, Assistant Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT01760226     History of Changes
Other Study ID Numbers: H-30759, DA-EPOCH-R, DA-EPOCH-R, 5K12CA090433-12
Study First Received: December 17, 2012
Last Updated: October 22, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Baylor College of Medicine:
B Cell lymphoma
lymphoma
Burkitt
DLBCL
Diffuse large B cell lymphoma
dose adjusted
EPOCH
Etoposide
Doxorubicin
Vincristine
Cyclophosphamide
Prednisone
Rituximab

Additional relevant MeSH terms:
Burkitt Lymphoma
Leukemia
Lymphoma
Lymphoproliferative Disorders
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Experimental
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Methotrexate
Rituximab
Etoposide phosphate
Doxorubicin
Etoposide
Prednisone
Vincristine
Lenograstim
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 23, 2014