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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


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Burkitt Lymphoma, Diffuse Large B-cell Lymphoma, c-MYC Positive

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Trial Information

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 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 >= 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 153 patients will be enrolled in the protocol.

Inclusion Criteria


- INCLUSION CRITERIA:

- Burkitt lymphoma or B-cell lymphoma, unclassifiable, with features intermediate
between Diffuse Large B-cell lymphoma** and Burkitt Lymphoma, c-MYC + DLBCL or c-MYC+
plasmablastic lymphoma by histology. For c-MYC + cases, a MYC rearrangement must be
documented 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 and/or cyclophosphamide
for an urgent problem at diagnosis (e.g. epidural cord compression, superior vena
cava syndrome).

- 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.

- In the interest of completing the CALGB 50303 study, Alliance members should
consider enrolling patients with a diagnosis of DLBCL onto the CALGB 50303
study.

EXCLUSION CRITERIA:

- 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.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine PFS, EFS and OS of risk adaptive DA-EPOCH-R in newly diagnosed Burkitt Lymphoma and c-MYC + DLBCL and DA-EPOCH in c-MYC+ plasmablastic lymphoma.

Outcome Time Frame:

8 years

Safety Issue:

No

Principal Investigator

Kieron M Dunleavy, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)

Authority:

United States: Federal Government

Study ID:

100052

NCT ID:

NCT01092182

Start Date:

February 2010

Completion Date:

March 2018

Related Keywords:

  • Burkitt Lymphoma
  • Diffuse Large B-cell Lymphoma, c-MYC Positive
  • Microarray
  • Toxicity
  • Therapeutic Index
  • HIV Positive
  • HIV Negative
  • Lymphoma
  • Burkitt Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • HIV Infections
  • Burkitt Lymphoma
  • Lymphoma
  • Lymphoma, B-Cell
  • Lymphoma, Large B-Cell, Diffuse

Name

Location

National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892
MD Anderson Cancer CenterHouston, Texas  77030-4096
Washington University School of MedicineSaint Louis, Missouri  63110
Beth Israel Deaconess Medical CenterBoston, Massachusetts  02215
Parma Community General HospitalParma, Ohio  44129
Massachusetts General HospitalBoston, Massachusetts  02114-2617
Menorah Medical CenterOverland Park, Kansas  66209
North Kansas City HospitalKansas City, Missouri  64116
Research Medical CenterKansas City, Missouri  64132
Saint Luke's East - Lee's SummitLee's Summit, Missouri  64086
Heartland Regional Medical CenterSaint Joseph, Missouri  64506
Fairview HospitalCleveland, Ohio  44111
HillCrest HospitalMayfield Heights, Ohio  44124
Providence Medical CenterKansas City, Kansas  66112
Cleveland ClinicCleveland, Ohio  44195
Dana Farber Cancer InstituteBoston, Massachusetts  02115
Mercy Medical Center-Sioux CitySioux City, Iowa  51104
Saint Luke's Regional Medical CenterSioux City, Iowa  51104
Saint Luke's Hospital of Kansas CityKansas City, Missouri  64111
Liberty Radiation Oncology ClinicKansas City, Missouri  64116
North Coast Cancer CareSandusky, Ohio  44870
Saint Luke's South HospitalOverland Park, Kansas  66213
Kansas City CCOPPrairie Village, Kansas  66208
Heartland Hematology and Oncology Associates IncorporatedKansas City, Missouri  64118
Saint Joseph Oncology IncSaint Joseph, Missouri  64507
Siouxland Hematology Oncology Associates LLPSioux City, Iowa  
Shawnee Mission Medical Center-KCCCShawnee Mission, Kansas  
Cleveland Clinic BeachwoodBeachwood, Ohio  
Cleveland Clinic Transplantation ClinicCleveland, Ohio  
Cleveland Clinic IndependenceIndependence, Ohio  
Cleveland Clinic StrongsvilleStrongsville, Ohio  
Cleveland Clinic WoosterWooster, Ohio