Phase II Study of Dose-Adjusted EPOCH-Rituximab in Adults With Untreated Burkitt Lymphoma and c-MYC+ Diffuse Large B-Cell Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT01092182
First received: March 23, 2010
Last updated: June 21, 2014
Last verified: May 2014
  Purpose

Background:

  • Burkitt lymphoma/leukemia (BL) is highly treatable, but most of the standard therapies require multiple doses of intensive chemotherapy that may require long hospital stays and frequently have severe side effects. In addition, BL is a fairly common type of cancer in patients who also have human immunodeficiency virus (HIV), but treatment outcomes are poor because standard treatments do not work very well in HIV-positive patients and the more intense treatment regimens are highly toxic. New approaches are needed that expand the ways to treat BL with the same efficiency but with reduced side effects.
  • DA-EPOCH-R is a standard chemotherapy treatment that consists of the drugs etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab. It may be able to treat BL with similar effectiveness but with fewer side effects. Researchers are interested in confirming the results of previous studies that investigated the effectiveness of DA-EPOCH-R in treating BL.

Objectives:

- To determine the safety and effectiveness of DA-EPOCH-R in treating Burkitt lymphoma.

Eligibility:

- Individuals at least 18 years of age who have been diagnosed with Burkitt lymphoma and have not had any prior chemotherapy treatments.

Design:

  • Individuals will have a series of blood and other tests to determine their suitability for participating in the study. Eligible participants will be divided into high-risk and low-risk groups based on their disease prognosis and the possibility that the BL may or already has spread into the central nervous system.
  • Participants will receive intravenous infusion of the six chemotherapy drugs in DA-EPOCH-R in 21-day treatment cycles. The exact doses will be adjusted depending on participants white blood cell counts and other tests.
  • High-risk participants will receive six cycles of DA-EPOCH-R. To treat BL that may have entered the central nervous system, high-risk participants will also receive infusions of other chemotherapy drugs into their spinal fluid.
  • Low-risk participants will receive up to six cycles of DA-EPOCH-R, with an additional dose of rituximab during each cycle.
  • Frequent blood and urine tests will be performed during treatment, as well as body imaging scans and other tests of cancer progression as directed by the study doctors. Participants will receive additional medicines to help prevent possible adverse side effects of DA-EPOCH-R.
  • Participants who respond successfully to the treatment will be asked to return for follow-up exams every 3 months for the first 18 months, then every year for the next 3 years. Participants who do not respond successfully to the treatment will be given the opportunity to participate in additional research and treatment protocols, if any are available.

Condition Intervention Phase
Burkitt Lymphoma
Diffuse Large B-cell Lymphoma, c-MYC Positive
Plasmablastic Lymphoma
Drug: EPOCH-R
Drug: EPOCH-RR
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Dose-Adjusted EPOCH+/-Rituximab in Adults With Untreated Burkitt Lymphoma, c-MYC Positive Diffuse Large B-Cell Lymphoma and Plasmablastic Lymphoma

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • PFS, EFS and OS [ Time Frame: Time of progression or death ] [ Designated as safety issue: No ]

Estimated Enrollment: 153
Study Start Date: February 2010
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Burkitt lymphoma Low Risk Arm
Drug: EPOCH-RR
EPOCH-R every 21 days for 3 cycles
Experimental: B
Burkitt lymphoma High Risk Arm
Drug: EPOCH-R
EPOCH-R every 21 days for 6 cycles
Experimental: C
DLBCL high risk arm
Drug: EPOCH-R
EPOCH-R every 21 days for 6 cycles

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Patients must have one of the following histologic diagnoses:

  • Burkitt lymphoma
  • B-cell lymphoma: unclassifiable with features intermediate between Diffuse Large B cell lymphoma and Burkitt Lymphoma
  • c-MYC + DLBCL. For these cases, a MYC rearrangement [(8,14) translocation by FISH or cytogenetics] must be confirmed before study enrollment
  • c-MYC+ plasmablastic lymphoma. For these cases, a MYC rearrangement [(8,14) translocation by FISH or cytogenetics] must be confirmed before study enrollment
  • If questions arise related to diagnosis, please contact the NCI PI, Dr. Dunleavy or the NCI study coordinator, A. Nicole Lucas
  • Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of EPOCH-R in patients < 18 years of age, children are excluded from this study, but may be eligible for future pediatric trials
  • Pathology confirmed by treating institution s Pathology Department.
  • No prior treatment except patients may be entered if they have had prior limited-field radiotherapy, a short course of glucocorticoids, cyclophosphamide for an urgent problem at diagnosis (e.g. epidural cord compression, superior vena cava syndrome) and/or a single dose of intrathecal methotrexate (MTX) at the time of the pre-treatment diagnostic lumbar puncture.
  • All disease stages.
  • HIV negative or positive.
  • HIV positive patients on antiretrovival therapy regimen must be willing to suspend all Highly Active Antiretroviral Therapy (HAART) except in circumstances described in section 6.5.
  • ECOG 0-4
  • Ability of patient or durable power of attorney (DPA) for healthcare to give informed consent.
  • Hepatitis B + patients may be enrolled at the discretion of the investigator.

EXCLUSION CRITERIA:

  • Patients with Primary CNS Lymphoma.
  • Inadequate renal function, defined as serum Cr > 1.5 or creatinine clearance < 50ml/min/1.73m2 unless lymphoma related.
  • Inadequate hepatic or hematological function: bilirubin greater than 2 mg/dl (total) except greater than 5 mg/dl in patients with Gilbert s syndrome as defined by greater than 80% unconjugated; ANC less than 1000 and platelets less than 75,000 unless lymphoma related.
  • The effects of EPOCH-R on the developing human fetus are unknown. For this reason and because chemotherapy agents are known to be teratogenic, female subject of child-bearing potential not willing to use an acceptable method of birth control(i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study and one year beyond treatment completion will not be eligible to participate in the study.
  • Female subject pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for women without child-bearing potential.
  • The effects of EPOCH-R on the developing human fetus are unknown. For this reason and because chemotherapy agents are known to be teratogenic, male subject unwilling to use an acceptable method for contraception for the duration of the study and one year beyond treatment completion, will not be eligible to participate in the study.
  • History of a prior invasive malignancy in past 5 years.
  • Active symptomatic ischemic heart disease, myocardial infarction or congestive heart failure within the past year. If echo is obtained the LVEF should exceed 40%.
  • Serious concomitant medical illnesses that would jeopardize the patient's ability to receive the regimen with reasonable safety.
  • HIV positive patients with advanced immune supression and evidence of HIV resistant to all combinations of antiretroviral therapy considered at high risk of non lymphoma related death within 12-months due to other AIDS complications should not be enrolled on the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01092182

Contacts
Contact: Margaret Shovlin, R.N. (301) 594-6597 mshovlin@mail.nih.gov
Contact: Kieron M Dunleavy, M.D. (301) 435-1007 dunleavk@mail.nih.gov

Locations
United States, Iowa
Mercy Medical Center-Sioux City Recruiting
Sioux City, Iowa, United States
Saint Luke's Regional Medical Center Recruiting
Sioux City, Iowa, United States
Siouxland Hematology Oncology Associates LLP Recruiting
Sioux City, Iowa, United States
United States, Kansas
Providence Medical Center Recruiting
Kansas City, Kansas, United States
Saint Luke's South Hospital Recruiting
Overland Park, Kansas, United States
Menorah Medical Center Recruiting
Overland Park, Kansas, United States
Kansas City CCOP Recruiting
Prairie Village, Kansas, United States
Shawnee Mission Medical Center-KCCC Recruiting
Shawnee Mission, Kansas, United States
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    (888) NCI-1937      
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States
United States, Missouri
North Kansas City Hospital Recruiting
Kansas City, Missouri, United States
Research Medical Center Recruiting
Kansas City, Missouri, United States
Liberty Radiation Oncology Clinic Recruiting
Kansas City, Missouri, United States
Saint Luke's Hospital of Kansas City Recruiting
Kansas City, Missouri, United States
Heartland Hematology and Oncology Associates Incorporated Recruiting
Kansas City, Missouri, United States
Saint Luke's East - Lee's Summit Recruiting
Lee's Summit, Missouri, United States
Saint Joseph Oncology Inc Recruiting
Saint Joseph, Missouri, United States
Heartland Regional Medical Center Recruiting
Saint Joseph, Missouri, United States
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States
United States, Ohio
Cleveland Clinic Beachwood Recruiting
Beachwood, Ohio, United States
Cleveland Clinic Transplantation Clinic Recruiting
Cleveland, Ohio, United States
Fairview Hospital Recruiting
Cleveland, Ohio, United States
Cleveland Clinic Recruiting
Cleveland, Ohio, United States
Cleveland Clinic Independence Recruiting
Independence, Ohio, United States
Hillcrest Hospital Recruiting
Mayfield Heights, Ohio, United States
Parma Community General Hospital Recruiting
Parma, Ohio, United States
North Coast Cancer Care Recruiting
Sandusky, Ohio, United States
Cleveland Clinic Strongsville Recruiting
Strongsville, Ohio, United States
Cleveland Clinic Wooster Recruiting
Wooster, Ohio, United States
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030-4096
Sponsors and Collaborators
Investigators
Principal Investigator: Kieron M Dunleavy, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT01092182     History of Changes
Other Study ID Numbers: 100052, 10-C-0052
Study First Received: March 23, 2010
Last Updated: June 21, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Microarray
Toxicity
Therapeutic Index
HIV Positive
HIV Negative
Lymphoma
Burkitt Lymphoma
Diffuse Large B-Cell Lymphoma
HIV Infections

Additional relevant MeSH terms:
Burkitt Lymphoma
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Immunoblastic
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Experimental
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 26, 2014