Peripheral T-cell Lymphoma Clinical Trial
Official title:
Phase I Dose-Escalation Study of Azacitidine (Vidaza) and Bortezomib (Velcade) in T-Cell Lymphoma
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.
Status | Completed |
Enrollment | 8 |
Est. completion date | December 2012 |
Est. primary completion date | May 2012 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
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 |
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
United States | Ohio State University Medical Center | Columbus | Ohio |
Lead Sponsor | Collaborator |
---|---|
Pierluigi Porcu | Celgene Corporation, Millennium Pharmaceuticals, Inc. |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Maximum tolerable dose (MTD) of bortezomib in combination with azacitidine | up to 28 days | Yes | |
Primary | Specific toxicities and the dose limiting toxicity (DLT) of bortezomib in combination with azacitidine as assessed by NCI CTCAE (Common Toxicity Criteria for Adverse Effects) v4.0 | up to 2 years | Yes | |
Secondary | Overall response rate | up to 2 years | No | |
Secondary | Correlation of the biological activity of Azacitidine as a demethylating agent with clinical endpoints and plasma pharmacokinetics | up to 2 years | No | |
Secondary | Biological activity of bortezomib as a potential demethylating agent | up to 2 years | No | |
Secondary | Correlation of intracellular concentration of azacitidine-triphosphate with global DNA methylation and other biological endpoints as well as clinical response | up to 2 years | No | |
Secondary | Biologic role of microRNAs in determining clinical response to the bortezomib plus azacitidine combination and achievement of the other pharmacodynamic endpoints | up to 2 years | No |
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