EPOCH Chemotherapy and Bortezomib for Associated T-Cell Leukemia Lymphoma

Inclusion Criteria:

• Histologically or cytologically documented ATLL. Patients with previously untreated ortreated ATLL are eligible.

• Tumors must be CD3 positive (>50% cells express CD3).

• Documented HTLV-1 infection: documentation may be serologic assay (ELISA, Westernblot) Confirmation of HTLV-1 rather than HTLV-2 by differential Western blot (e.g.Genelabs Diagnostics HTLV Blot 2.4) or PCR is desirable but his result is not requiredprior to trial enrollment.

• Measurable disease must be present. These nodes or masses should be selected accordingto all of the following: they should be clearly measurable in at least twoperpendicular dimensions; if possible they should be from disparate regions of thebody; and they should include mediastinal and retroperitoneal areas of diseasewhenever these sites are involved.For patients with acute (leukemic) form of ATLL,measureable disease can be derived from CD4+ lymphocyte flow data on the peripheralblood and/or bone marrow.

• All stages are eligible.

• Adequate hematologic function within 14 days before enrollment: ANC>1000 cells/mm3,platelet count>75,000 cells/mm3 unless cytopenias are secondary to ATLL. All patientsmust be off hematologic growth factors for at least 24 hrs.

• Adequate hepatic function, transaminase <3 times the upper limit of normal unless dueto to Gilbert's disease or hepatic involvement by tumor; total bilirubin ≤1.5 timesthe upper limit of normal

• Creatinine<2.0 unless due to lymphoma.

• Karnofsky Performance Status (KPS) at least 50

• Age at least 18. -Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consentmay be withdrawn by the subject at any time without prejudice to future medical care.

• Female patients of child bearing potential must have a negative pregnancy test within 72 hrs of initiation of therapy. Female patients are either post-menopausal orsurgically sterilized or willing to use two acceptable methods of birth control (i.e.,a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom withspermicide, or abstinence) during the study. Male patients must agree to use twoacceptable methods for contraception for the duration of the study. Women must avoidpregnancy and men avoid fathering children while in the study.

• HIV positive patients are eligible if they are receiving at least two other activeanti-HIV therapies other than zidovudine or atazanavir.

• Patients with active hepatitis B (HBV) infection are eligible if they are receivingeffective anti-HBV therapy.

• Inclusion of Women and Minorities: Both men and women and members of all races andethnic groups are eligible for this trial.

Exclusion Criteria:

• Acute active infection requiring acute therapy. Chronic therapy with potentiallymyelosuppressive agents is allowed provided that entry hematologic criteria are met.

• Diagnosed or treated for another malignancy within 3 years of enrollment, with theexception of complete resection of basal cell carcinoma or squamous cell carcinoma ofthe skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.

• Women who are pregnant or breastfeeding. Confirmation that the subject is not pregnantmust be established by a negative serum B-human chorionic gonadotropin (B-hCG)pregnancy test result obtained during screening. Pregnancy testing is not required forpost-menopausal or surgically sterilized women.

• Patient has ≥Grade 2 peripheral neuropathy

• Myocardial infarction within 6 months prior to enrollment or has New York HeartAssociation (NYHA) Class III or IV heart failure, uncontrolled angina, severeuncontrolled ventricular arrhythmias, or electrocardiographic evidence of acuteischemia or active conduction system abnormalities. Prior to study entry, anyelectrocardiogram (ECG) abnormality at Screening has to be documented by theinvestigator as not medically relevant.

• Patient has hypersensitivity to bortezomib, boron or mannitol.

• Patient has received other investigational drugs with 14 days before enrollment

• Serious medical or psychiatric illness likely to interfere with participation in thisclinical study.

• 1.5x upper limit of normal (ULN) total bilirubin except if is determined to berelated to Gilbert's disease or tumor biliary/liver involvement.