A Phase 1/2, Open-Label, Multicenter Study of ACY-1215 Administered Orally as Monotherapy and in Combination With Bortezomib and Dexamethasone for the Treatment of Relapsed or Relapsed/Refractory Multiple Myeloma
- 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
- 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
- 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.
- 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)