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



Status:Active, not recruiting
Conditions:Lymphoma
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - 100
Updated:2/22/2019
Start Date:February 24, 2010
End Date:February 28, 2023

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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.

- 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 Principal Investigator, Dr.
Mark Roschewski 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: as follows, unless
lymphoma-/disease-related: 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.

- 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.
We found this trial at
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330 Brookline Ave
Boston, Massachusetts 02215
617-667-7000
Beth Israel Deaconess Medical Center Beth Israel Deaconess Medical Center (BIDMC) is one of the...
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9500 Euclid Avenue
Cleveland, Ohio 44106
216.444.2200
Cleveland Clinic Cleveland Clinic is committed to principles as presented in the United Nations Global...
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200 North Park Street
Kalamazoo, Michigan 49007
(269) 382-2500
West Michigan Cancer Center In 1994, Borgess Health Alliance and Bronson Healthcare Group opened the...
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60 Crittenden Blvd # 70
Rochester, New York 14642
(585) 275-2121
University of Rochester The University of Rochester is one of the country's top-tier research universities....
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9000 Rockville Pike
Bethesda, Maryland 20892
Phone: (888) NCI-1937
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450 Brookline Ave
Boston, Massachusetts 2215
617-632-3000
Dana-Farber Cancer Institute Since it’s founding in 1947, Dana-Farber has been committed to providing adults...
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Boston, Massachusetts 02114
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1200 West Harrison Stree
Chicago, Illinois 60607
(312) 996-4350
Univ of Illinois A major research university in the heart of one of the world's...
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10900 Euclid Ave
Cleveland, Ohio 44106
216-368-2000
Case Western Reserve Univ Continually ranked among America's best colleges, Case Western Reserve University has...
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2500 Metrohealth Dr
Cleveland, Ohio 44109
(216) 778-7800
MetroHealth Med Ctr The MetroHealth System is one of the largest, most comprehensive health care...
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6401 France Ave S
Edina, Minnesota 55435
(952) 924-5000
Fairview Southdale Hospital Fairview Health Services is an award-winning nonprofit health care system based in...
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550 Osborne Rd NE
Fridley, Minnesota 55432
(763) 236-5000
Unity Hospital Unity Hospital is one of the Twin Cities
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Houston, Texas 77030
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600 Moye Boulevard
Kinston, North Carolina 28501
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Knoxville, Tennessee 37996
(865) 974-1000
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3855 Health Sciences Dr,
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600 Highland Ave
Madison, Wisconsin 53792
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9200 W Wisconsin Ave
Milwaukee, Wisconsin 53226
(414) 805-3666
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New York, New York 10017
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1275 York Ave
New York, New York 10021
(212) 639-2000
Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center — the world's oldest and...
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Emile St
Omaha, Nebraska 68198
(402) 559-4000
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660 S Euclid Ave
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3850 Park Nicollet Blvd
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1 Medical Center Blvd
Winston-Salem, North Carolina 27157
336-716-2011
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