Bortezomib and Azacitidine in Treating Patients With Relapsed or Refractory T-Cell Lymphoma

• Status: Completed
• Trial end date: 2012-12-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Bortezomib and azacitidine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given together with azacitidine in treating patients with relapsed or refractory T-cell lymphoma.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Pierluigi Porcu
• Collaborators: Celgene Corporation; Millennium Pharmaceuticals, Inc.
• Treatments: Azacitidine; Bortezomib

Criteria

Inclusion Criteria:

• Patients must have pathologically documented T-cell lymphoma belonging to one of the following WHO entities: Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS); Mycosis Fungoides and Sezary Syndrome (MF-SS); Angioimmunoblastic T-cell lymphoma (AITL); CD30-positive Anaplastic Large Cell Lymphoma (ALCL), systemic; T/NK-cell lymphoma, extranodal, nasal and nasal type; Hepatosplenic T-cell lymphoma, gamma/delta or alpha/beta; Enteropathy-associated T-cell lymphoma (EATL); Adult T-cell Leukemia/Lymphoma (ATLL); Subcutaneous panniculitis-like T-cell lymphoma (SCPTCL); Blastic T/NK-cell lymphoma/leukemia (CD4+CD56+ Hematodermic Tumor); T/NK-cell post-transplant lymphoproliferative disorders (PTLD); Large Granular Lymphocyte (LGL) Leukemia; T-cell Prolymphocytic Leukemia (T-PLL)

• Patients must have relapsed or refractory TCL

• Patients must have failed at least one prior systemic therapy

• Life expectancy must be greater than 3 months

• Eastern Cooperative Oncology Group (ECOG) performance status =< 2

• Patients must have adequate organ function as defined below:

• Total bilirubin < 1.5 x upper limit of normal (ULN)

• AST(aspartate aminotransferase) < 2.0 x ULN

• ALT(Alanine transaminase) < 2.0 x ULN

• Serum creatinine < 1.5 ULN

• New York Heart Association Congestive Heart Failure (NYHA CHF) Class II or better

• Platelet count >= 75,000/mm^3 (unless due to disease) within 14 days before enrollment

• Absolute neutrophil count of >= 1,500/mm^3 within 14 days before enrollment

• Women of childbearing potential must have a negative serum pregnancy test prior to azacitidine treatment; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; if the patient does not agree, the patient is not eligible; women must agree to not get pregnant for the duration of the study; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform the PI or the Study Nurse immediately

• Ability to understand and willingness to sign the written informed consent document before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care

• Male subject agrees to use an acceptable method for contraception for the duration of the study

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study

• Patients receiving any other investigational agents or patients who have received other investigational agents within 14 days of enrollment

• Patients with active central nervous system (CNS) malignancy

• Patients with history of allergic reactions attributed to compounds of similar chemical or biologic composition to Azacitidine or VELCADE (BORTEZOMIB) that are not easily managed; patients with hypersensitivity to VELCADE (BORTEZOMIB), boron, or mannitol

• Patients must not have previously received Azacitidine or VELCADE (BORTEZOMIB) for any disease

• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; as infection is a common feature of TCL, patients with active infection are permitted to enroll provided that the infection is under control; myocardial infarction within 6 months prior to enrollment or has NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant

• Pregnant women or women who are breastfeeding are excluded from this study; 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 post-menopausal or surgically sterilized women

• HIV-positive patients are ineligible; all patients will be screened for HIV

• Patients with pre-existing Grade 2 or higher neuropathy within 14 days before enrollment or other serious neurologic toxicity that would significantly increase risk of complications from VELCADE (BORTEZOMIB) therapy are excluded

• Patients with active, advanced malignant solid tumors are excluded

• Patients with serious medical or psychiatric illness likely to interfere with participation in this clinical study

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