Study of ACY-1215 in Combination With Lenalidomide, and Dexamethasone in Multiple Myeloma

Inclusion Criteria:

• Relapsed or Relapsed/Refractory MM with progressive disease (PD) according to IMWG.
• Received at least 1 prior line of therapy for MM
• Not a candidate for autologous stem cell transplant (ASCT) or declined option.
• Karnofsky Performance Status score ≥ 70
• Adequate bone marrow reserve as evidenced by ANC > 1.0x109/L;Platelet > 50x109/L
• Creatinine Clearance of ≥ 60 mL/min
• Adequate hepatic function as evidenced by serum bilirubin values < 2.0 mg/dL; ALT and/or AST < 3xULN.
• Corrected serum calcium ≤ ULN
• Able to take acetylsalicylic acid (ASA) (81 or 325 mg) daily as prophylactic anticoagulation. Coumadin will be allowed provided the patient is fully anticoagulated, with an INR of 2 or 3.
• Agreement to participate in RevAssist® Program
• Female of childbearing potential must have a negative pregnancy test 10-14 days prior to and again within 24 hours of prescribing lenalidomide for Cycle 1 and must either commit to continued abstinence or begin TWO acceptable methods of birth control.
• If male, including those who have had a vasectomy, must agree to use a latex condom during any sexual contact with a female of childbearing potential.

Exclusion Criteria:

• Received any of the following antitumor therapies

  • Radiotherapy or systemic therapy within 2 weeks of Cycle 1 Day 1 (C1D1)
  • Investigational or biologic therapies within 3 weeks of C1D1
  • Prior peripheral ASCT within 12 weeks of C1D1
  • Prior allogeneic stem cell transplant
  • Prior treatment with a histone deacetylase (HDAC) inhibitor
• Presence of an active systemic infection requiring treatment.
• History of other malignancies unless the patient has undergone definitive treatment more than 5 yr prior, excluding basal cell carcinoma of the skin; superficial carcinoma of the bladder; carcinoma of the prostate with current prostat specific antigen < 0.1 ng/mL; ductal carcinoma in situ; or cervical intraepithelial neoplasia.
• Known or suspected human immunodeficiency virus (HIV), hepatitis B surface antigen-positive status or known or suspected active hepatitis C.
• History of significant cardiovascular, neurological, endocrine, gastrointestinal, respiratory, or inflammatory illness including but not limited to congestive heart failure (NYHA Class 3 or 4), unstable angina; cardiac arrhythmia, recent(within past 6 months) myocardial infarction or stroke; uncontrolled hypertension; diabetes mellitus with > 2 episodes of ketoacidosis in the preceding 12 months, COPD requiring > 2 hospitalizations in preceding 12 months
• QTcF > 480 msec, family or personal history of long QTc syndrome or ventricular bigeminy; previous history of drug-induced QTc prolongation or the need for medications known or suspected of producing prolonged QTc intervals on ECG
• Documented plasma cell leukemia or known amyloidosis.
• Known hypersensitivity to thalidomide or lenalidomide.
• History of erythema nodosum characterized by desquamating rash while taking thalidomide or similar drugs.