EPOCH Chemotherapy and Bortezomib for Associated T-Cell Leukemia Lymphoma (ATLL)
|Leukemia-Lymphoma, Adult T-Cell||Drug: Bortezomib Drug: Etoposide Drug: Vincristine Drug: Doxorubicin Drug: Prednisone Drug: Cyclophosphamide Drug: Raltegravir||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (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|
- Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events [ Time Frame: Up to 30 days after completion of treatment ]The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for all toxicity reporting.
- Efficacy of Treatment as Measured by Best Overall Response [ Time Frame: Up to 4 years following completion of therapy ]-The response definitions used for this study are the 2007 Cheson criteria.
- Time to Progression [ Time Frame: Up to 4 years following completion of therapy ]-The progression definitions used for this study are from the 2007 Cheson criteria.
- Effects of on HTLV-1 DNA After Treatment as Measured by Proviral Loads [ Time Frame: 6 months ]
- Relation of NFκB Gene Expression Profile on Response [ Time Frame: 6 months ]Standard error represents the standard error of the fold expression of protein coding transcripts for each gene indicated.
- Effects of HTLV-1 RNA Load After Treatment as Measured by Hbz Messenger RNA [ Time Frame: 6 months ]
- Effects of HTLV-1 Integrase Gene Sequence After Treatment as Measured by Nucleotide Divergence [ Time Frame: 6 months ]
- Effects of HTLV-1 Integration Sites After Treatment [ Time Frame: 6 months ]
|Study Start Date:||September 2010|
|Study Completion Date:||April 2016|
|Primary Completion Date:||May 2014 (Final data collection date for primary outcome measure)|
Experimental: Arm 1
Bortezomib 1.0 mg/m2 intravenous (IV) Days 1-4
Etoposide 50 mg/m2/d 96 hour continuous intravenous infusion (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 twice per day (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|