A Phase 1, Open Label, Multicenter Study of ACY-1215 in Combination With Lenalidomide and Dexamethasone for the Treatment of Relapsed or Relapsed/Refractory Multiple Myeloma
- 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.
- 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.