Bortezomib, Vorinostat and Dexamethasone for Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)

Exclusion Criteria

• •Cytotoxic therapy: Patients must have had their last dose of chemotherapy at least two weeks prior to study entry.
• •Hematopoietic growth factors: At least 7 days since the completion of therapy with a growth factor and at least 14 days since pegfilgrastim (Neulasta®) administration.
• •Biologic (anti-neoplastic) therapy: At least 7 days since the completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair.
• •Monoclonal antibodies: At least 3 half-lives of the antibody after the last administration of a monoclonal antibody.
• •Hematopoietic Stem Cell Transplant (HSCT): Patients who have experienced their relapse after a HSCT are eligible, provided they have no evidence of Graft-versus-Host Disease (GVHD).
• •* Women of child bearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device \[IUD\], surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of treatment and for 2 months after the last dose of chemotherapy. Sexually active men must agree to use barrier contraceptive for the duration of treatment and for 2 months after the last dose of chemotherapy.
• •* Voluntary written consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject/guardian at any time without prejudice to future medical care.
• •Pregnant or lactating. The agents used in this study are known to be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. 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 surgically sterilized women.
• •Known hypersensitivity to bortezomib, boron or mannitol or any of the agents or their ingredients used in this study.
• •Inability to swallow capsules.
• •Grade 2 or greater peripheral neuropathy within 14 days before study registration.
• •Patients with untreated positive blood cultures or progressive infections as assessed by radiographic studies.
• •Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (appendix VI), 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.
• •Serious concomitant medical or psychiatric disorders (e.g., active infection, uncontrolled diabetes) that, in the opinion of the investigator, would compromise the safety of the patient or 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.
• •Patient has received investigational drugs within the 14 days before study registration.
• •Radiation therapy within 3 weeks before registration. Enrollment of patients who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy.