EPOCH Chemotherapy and Bortezomib for Associated T-Cell Leukemia Lymphoma (ATLL)
The rationale of the current study is to explore the use of combination chemotherapy together with antiretroviral agents in order to determine the efficacy and toxicity of this approach, while also examining markers of virus replication and expression, and tumor cell proliferation to gain understanding of the biological basis of this malignancy and to identify predictors of response.
Leukemia-Lymphoma, Adult T-Cell
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Trial of Dose-Adjusted EPOCH Chemotherapy With Bortezomib Combined With Integrase Inhibitor Therapy for HTLV-1 Associated T-Cell Leukemia Lymphoma|
- To determine the tolerability and efficacy of dose adjusted bortezomib-EPOCH (DA B-EPOCH) chemotherapy combined with Raltegravir in ATLL patients [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]A sequential probability ratio test will be used to monitor the frequency of patients who fail to complete 2 cycles of chemo-antiviral therapy due to toxicity.
- To determine the duration of response of DA B-EPOCH chemotherapy combined with Raltegravir for HTLV-1 associated leukemia/lymphoma (ATLL [ Time Frame: Up to 4 years following completion of therapy ] [ Designated as safety issue: No ]
- To evaluate the effects of DA B-EPOCH chemo combined with Raltegravir on HTLV-1 DNA and RNA load, HTLV-1 integrase gene sequence, and HTLV-1 integration sites. To determine if relapsed or progressive disease is a result of renewed virus replication. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- To evaluate the relation of NFκB gene expression profile on response to DA B-EPOCH chemotherapy combined with Raltegravir. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
|Study Start Date:||September 2010|
|Estimated Study Completion Date:||April 2018|
|Primary Completion Date:||May 2014 (Final data collection date for primary outcome measure)|
Experimental: Arm 1
Bortezomib 1.0 mg/m2 IV Days 1-4
Etoposide 50 mg/m2/d 96 hour CIVI on Days 1-4
Vincristine 0.4 mg/m2/d 96 hour CIVI on Days 1-4
Doxorubicin 10 mg/m2/d 96 hour CIVI on Days 1-4
Prednisone 60 mg/m2/d PO on Days 1-5
Cyclophosphamide 375 mg/m2 IV on Day 5
Raltegravir 400 mg PO BID every day starting with cycle 2 therapy for the entire duration of the cycle.
Cycles will be repeated every 21-28 days for 2 cycles beyond best response, or a maximum of 6 cycles.
Other Name: Velcade®Drug: Etoposide
Other Name: Toposar®, VePesid®, Etopophos®Drug: Vincristine
Other Name: Oncovin ®, Vincasar Pfs ®Drug: Doxorubicin
Other Name: Adriamycin ®, Rubex ®Drug: Prednisone
Other Name: Deltasone®, Liquid Pred®, Meticorten®, Orasone®Drug: Cyclophosphamide
Other Name: Cytoxan ®, Neosar ®Drug: Raltegravir
Other Name: Isentress®
- To determine the tolerability and efficacy (response rate) of dose adjusted bortezomib-EPOCH (DA B-EPOCH) chemotherapy combined with Raltegravir in patients with HTLV-1 associated leukemia/lymphoma (ATLL).
- To evaluate the effects of DA B-EPOCH chemotherapy combined with Raltegravir on HTLV-1 DNA and RNA load, HTLV-1 integrase gene sequence, and HTLV-1 integration sites. To determine if relapsed or progressive disease is a result of renewed virus replication.
- To evaluate the relation of NFκB gene expression profile on response to DA B-EPOCH chemotherapy combined with Raltegravir.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01000285
|United States, Florida|
|University of Miami Hospital/Sylvester|
|Miami, Florida, United States, 33136|
|United States, Maryland|
|Johns Hopkins University|
|Baltimore, Maryland, United States, 21231|
|United States, Missouri|
|Washington University School of Medicine|
|St. Louis, Missouri, United States, 63110|
|United States, New York|
|Montefiore Medical Center|
|Bronx, New York, United States, 10467|
|Columbia University, College of Physicians and Surgeons|
|New York, New York, United States, 10032|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Lee Ratner, M.D., Ph.D.||Washington University School of Medicine|