study of acy-1215 alone and in combination with bortezomib and dexamethasone in multiple myeloma

Conditions: Multiple Myeloma

Summary: phase 1(a \& b): to evaluate the side effects and determine the best dose of oral acy-1215 as monotherapy, and also in combination with bortezomib and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma. phase 2a: to determine the objective response rate of oral acy-1215 in combination with bortezomib and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma.


Eligibility criteria:
inclusion criteria: * patient has relapsed or relapsed/refractory mm with measurable disease parameters according to the international myeloma working group (imwg) criteria * refractory is defined as experiencing less than minimal response (mr) to or progressive disease (pd) within 60 days after completion of the most recent anti-mm regimen * relapsed is defined as experiencing pd that requires therapy but which is not refractory following the achievement of stable disease (sd) or better to the most recent anti-mm regimen. * patient received at least 2 prior regimens for mm. * patient received prior treatment for mm with a proteasome inhibitor and an immunomodulatory drug, unless not a candidate for a proteasome inhibitor or an immunomodulatory drug. * patient either is not a candidate for autologous stem cell transplant (asct), has declined the option of asct, or has relapsed after prior asct. * patient is ≥18 years of age. * patient has a karnofsky performance status score of ≥70 * patient has adequate bone marrow reserve, as evidenced by: * absolute neutrophil count (anc) of ≥1.0x109/l. * platelet count of ≥ 75x109/l in patients in whom \<50% of bone marrow nucleated cells are plasma cells and ≥50x109/l in patients in whom more than 50% of bone marrow nucleated cells are plasma cells. * patient has adequate renal function (calculated creatinine clearance of ≥30 ml/min according to the cockroft-gault) * patient has adequate hepatic function (serum bilirubin values \<2.0 mg/dl and alt and/or ast values \<3 × the upper limit of normal uln). * patient has a corrected serum calcium ≤uln. exclusion criteria * patient has received any of the following therapies: * radiotherapy or systemic therapy within 2 weeks of baseline * prior peripheral autologous stem cell transplant within 12 wks of baseline. * prior allogeneic stem cell transplant. * prior treatment with an hdac inhibitor. * patient has an active systemic infection requiring treatment. * patient has a history of other malignancies unless has undergone definitive treatment more than 5 yrs prior to study and without evidence of recurrent malignant disease (excluding basal cell carcinoma of the skin; superficial carcinoma of the bladder; carcinoma of the prostate with a current prostate-specific antigen \<0.1 ng/ml; or cervical intraepithelial neoplasia). * patient has known or suspected hiv, positive for hepatitis b or is known or suspected to have active hepatitis c infection. * patient has a history of significant cardiovascular, neurological, endocrine, gastrointestinal, respiratory, or inflammatory illness including recent myocardial infarction (within 6 months)or stroke; hypertension requiring \>2 medications for adequate control; diabetes mellitus with \>2 episodes of ketoacidosis in the preceding 12 months; or chronic obstructive pulmonary disease (copd) requiring \>2 hospitalizations in the preceding 12 months. * patient has a qtcf value of \>480 msec; family or personal history of long qtc syndrome or ventricular arrhythmias including ventricular bigeminy; previous history of drug-induced qtc prolongation * patient has \> grade 2 painful neuropathy or peripheral neuropathy * patient has a history of allergic reaction attributable to bortezomib or other compounds containing boron or mannitol (phase 1b and 2a only)