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
- 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.
- 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.
-Burkitt lymphoma, c-MYC + DLBCL and c-MYC + plasmablastic lymphoma age >= 18
-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.
-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.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
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.
Kieron M Dunleavy, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|
|MD Anderson Cancer Center||Houston, Texas 77030-4096|
|Washington University School of Medicine||Saint Louis, Missouri 63110|
|Beth Israel Deaconess Medical Center||Boston, Massachusetts 02215|
|Parma Community General Hospital||Parma, Ohio 44129|
|Massachusetts General Hospital||Boston, Massachusetts 02114-2617|
|Menorah Medical Center||Overland Park, Kansas 66209|
|North Kansas City Hospital||Kansas City, Missouri 64116|
|Research Medical Center||Kansas City, Missouri 64132|
|Saint Luke's East - Lee's Summit||Lee's Summit, Missouri 64086|
|Heartland Regional Medical Center||Saint Joseph, Missouri 64506|
|Fairview Hospital||Cleveland, Ohio 44111|
|HillCrest Hospital||Mayfield Heights, Ohio 44124|
|Providence Medical Center||Kansas City, Kansas 66112|
|Cleveland Clinic||Cleveland, Ohio 44195|
|Dana Farber Cancer Institute||Boston, Massachusetts 02115|
|Mercy Medical Center-Sioux City||Sioux City, Iowa 51104|
|Saint Luke's Regional Medical Center||Sioux City, Iowa 51104|
|Saint Luke's Hospital of Kansas City||Kansas City, Missouri 64111|
|Liberty Radiation Oncology Clinic||Kansas City, Missouri 64116|
|North Coast Cancer Care||Sandusky, Ohio 44870|
|Saint Luke's South Hospital||Overland Park, Kansas 66213|
|Kansas City CCOP||Prairie Village, Kansas 66208|
|Heartland Hematology and Oncology Associates Incorporated||Kansas City, Missouri 64118|
|Saint Joseph Oncology Inc||Saint Joseph, Missouri 64507|
|Siouxland Hematology Oncology Associates LLP||Sioux City, Iowa|
|Shawnee Mission Medical Center-KCCC||Shawnee Mission, Kansas|
|Cleveland Clinic Beachwood||Beachwood, Ohio|
|Cleveland Clinic Transplantation Clinic||Cleveland, Ohio|
|Cleveland Clinic Independence||Independence, Ohio|
|Cleveland Clinic Strongsville||Strongsville, Ohio|
|Cleveland Clinic Wooster||Wooster, Ohio|