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: September 27, 2014
Last verified: May 2014

March 23, 2010
September 27, 2014
February 2010
December 2016   (final data collection date for primary outcome measure)
PFS, EFS and OS [ Time Frame: Time of progression or death ] [ Designated as safety issue: No ]
PFS, EFS and OS of risk adaptive DA-EPOCH-R in newly diagnosed Burkitt Lymphoma and c-MYC + DLBCL [ Time Frame: 8 years ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01092182 on ClinicalTrials.gov Archive Site
Not Provided
Assess predictive value of early FDG-PET scans on PFS. Obtain pilot comparative molecular profiling in HIV negative and positive BL and c-MYC + DLBCL. [ Time Frame: 6 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Phase II Study of Dose-Adjusted EPOCH-Rituximab in Adults With Untreated Burkitt Lymphoma and c-MYC+ Diffuse Large B-Cell Lymphoma
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

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.

Background:

  • Burkitt lymphoma/leukemia (BL) is highly curable. Standard treatment employs doseintense multi-agent chemotherapy and though effective is associated with high morbidity. Therefore, novel approaches are needed that improve the therapeutic index of BL while maintaining or improving efficacy. In HIV+ BL, outcome has been poor, mainly due to the use of CHOP based regimens in this disease.
  • Two NCI phase II trials have used EPOCH chemotherapy with 1 or 2 doses of rituximab (R) per cycle in untreated BL. (Dose-adjusted) DA-EPOCH-Rituximab has been used in16 HIV negative BL, and 8 HIV positive patients have received 3 to 4 cycles of EPOCHRR to minimize toxicity and risk of opportunistic infections. All patients remain in continuous remission. Treatment was very well tolerated and represents a novel therapeutic strategy in BL.
  • This trial seeks to assess the effectiveness of a risk adaptive approach with DA-EPOCHR

in untreated BL (HIV+/-). Because this treatment represents a major conceptual

departure from standard treatment, it is important to obtain additional Phase II results in

limited/advanced stage BL

-c-MYC positive DLBCL is a rare variant of DLBCL. There is very little data on the biology of this disease and what the optimal therapeutic approach should be has not been

defined. Therefore, based on our impression that this behaves aggressively and is likely characterized by a high tumor proliferation rate, we plan to accrue patients with this disease in addition to BL patients.

-Plasmablastic lymphoma, another variant of DLBCL is frequently characterized by the activation of MYC and has had a poor outcome historically with standard treatment. We plan to include these patients in the study also. As they are CD20 negative, they will

receive DA-EPOCH without Rituximab.

Objectives:

  • Determine PFS, EFS and OS of risk adaptive DA-EPOCH-R in untreated BL and c-MYC + DLBCL and DA-EPOCH in c-MYC+ plasmablastic lymphoma.
  • Assess predictive value of early FDG-PET/CT scans on PFS.
  • Obtain pilot comparative molecular profiling in HIV negative and positive BL and c- MYC + DLBCL, including c-MYC+ plasmablastic lymphoma.

Eligibility:

-Burkitt lymphoma, c-MYC + DLBCL and c-MYC + plasmablastic lymphoma age (Bullet) 18

years.

-No prior treatment except limited-field radiotherapy, short course of glucocorticoids

and/or cyclophosphamide for an urgent problem at diagnosis.

-Adequate major organ function unless impairment due to lymphoma.

Study Design:

-Phase II Study of risk adapted DA-EPOCH-R in BL, c-MYC + DLBCL and DA-EPOCH

in c-MYC+ plasmablastic lymphoma

  • Low risk: DA-EPOCH-RR x 3 cycles.
  • High risk , c-MYC + DLBCL and c-MYC+ plasmablastic lymphoma : DA-EPOCH (+/-) R x 6 cycles or 8 cycles in select patients.
  • CSF cytology and flow cytometry for analysis of BL.
  • High Risk CSF negative - Prophylactic intrathecal treatment
  • CSF positive - Active intrathecal treatment
  • FDG-PET/CT pre- and post-cycle 2 in all patients.
  • A total of 194 patients will be enrolled in the protocol.
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Burkitt Lymphoma
  • Diffuse Large B-cell Lymphoma, c-MYC Positive
  • Plasmablastic Lymphoma
  • Drug: EPOCH-R
    EPOCH-R every 21 days for 6 cycles
  • Drug: EPOCH-RR
    EPOCH-R every 21 days for 3 cycles
  • Experimental: A
    Burkitt lymphoma Low Risk Arm
    Intervention: Drug: EPOCH-RR
  • Experimental: B
    Burkitt lymphoma High Risk Arm
    Intervention: Drug: EPOCH-R
  • Experimental: C
    DLBCL high risk arm
    Intervention: Drug: EPOCH-R

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
194
December 2017
December 2016   (final data collection date for primary outcome measure)
  • INCLUSION CRITERIA:

Patients must have one of the following histologic diagnoses:

-Patients must have Burkitt Lymphoma. Effective with Amendment J (version date: 06/24/2014), the following histologies were removed as the maximum number allowed for these sub-groups has been reached: B-cell lymphoma: unclassifiable with features intermediate between Diffuse Large B cell lymphoma and Burkitt Lymphoma ; c-MYC + DLBCL and c-MYC+ plasmablastic lymphoma.

If questions arise related to diagnosis, please contact the NCI PI, Dr. Dunleavy or theNCI 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.
Both
18 Years and older
No
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
United States
 
NCT01092182
100052, 10-C-0052
Not Provided
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Kieron M Dunleavy, M.D. National Cancer Institute (NCI)
National Institutes of Health Clinical Center (CC)
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP