ACY-1215 (Ricolinostat) in Combination With Pomalidomide and Low-dose Dex in Relapsed-and-Refractory Multiple Myeloma

Inclusion Criteria:

- Must have a documented diagnosis of multiple myeloma and have relapsed-and-refractory
disease. Patients must have received at least 2 lines of prior therapies. Patients
must have relapsed after having achieved at least stable disease (SD) for at least one
cycle of treatment to at least one prior regimen and then developed progressive
disease (PD). Patients must also have documented evidence of PD during or within 60
days (measured from the end of the last cycle) of completing treatment with the last
anti-myeloma drug regimen used just prior to study entry (refractory disease)

- Must have undergone prior treatment with at least 2 cycles of lenalidomide and at
least 2 cycles of a proteasome inhibitor (either in separate regimens or within the
same regimen)

- Must not be a candidate for autologous stem cell transplant (ASCT), has declined the
option of ASCT, or has relapsed after prior ASCT

- Must have measurable levels of myeloma paraprotein in serum (≥ 0.5 g/dL) or urine (≥
0.2 g/24 hours)

- Must have Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1,
or 2

- Females of child bearing potential (FCBP) must have a negative serum or urine
pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to,
and again within 24 hours of starting pomalidomide and must either commit to continued
abstinence from heterosexual intercourse or begin TWO acceptable methods of birth
control, one highly effective method and one additional effective method AT THE SAME
TIME, at least 28 days before she starts taking pomalidomide. FCBP must also agree to
ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact
with a FCBP even if they have had a vasectomy. All patients must be counseled at a
minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control
Methods,and Education and Counseling Guidance must be followed per protocol

- Must be able to take acetylsalicylic acid (ASA) (81 or 325 mg) daily as prophylactic
anticoagulation. Patients intolerant to ASA may use low molecular weight heparin.
Lovenox is recommended. Coumadin will be allowed provided the patient is fully
anticoagulated, with an international normalized ratio (INR) of 2 to 3

Exclusion Criteria:

- Pregnant or lactating females

- Prior therapy with HDAC inhibitor

- Any of the following laboratory abnormalities:

- ANC < 1,000/µL

- Platelet count < 75,000/ µL for patients in whom < 50% of bone marrow nucleated
cells are plasma cells; and < 50,000/ µL for patients in whom ≥ 50% of bone
marrow nucleated cells are plasma cells

- Hemoglobin < 8g/dL (<4.9 mmol/L; prior red blood cell [RBC] transfusion is
permitted)

- Creatine clearance < 45mL/min according to Cockcroft-Gault formula. If creatine
clearance calculated from the 24-hour urine sample is ≥ 45 mL/min, patient will
qualify for the study

- Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST),
or serum glutamic pyruvic transaminase (SGPT)/ alanine aminotransferase (ALT) >
3.0 × ULN

- Serum total bilirubin > 2.0 mg/dL

- Prior history of malignancies, other than MM, unless the patient has been free of the
disease for ≥ 3 years. Exceptions include the following:

- Basal or squamous cell carcinoma of the skin

- Carcinoma in situ of the cervix or breast

- Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)

- Corrected QT interval using Fridericia's formula (QTcF) value > 480 msec at screening;
family or personal history of long QTc syndrome or ventricular arrhythmias including
ventricular bigeminy; previous history of drug-induced QTc prolongation or the need
for treatment with medications known or suspected of producing prolonged QTc intervals
on electrocardiogram (ECG)

- Positive human immunodeficiency virus (HIV), hepatitis B virus (HBV) and/or hepatitis
C virus (HCV) infection

- Hypersensitivity to thalidomide, lenalidomide, or dexamethasone (such as Steven
Johnson Syndrome). Hypersensitivity, such as rash, that can be medically managed is
allowable

- Peripheral neuropathy ≥ Grade 2 despite supportive therapy

- Radiotherapy or systemic therapy (standard or an investigational or biologic
anticancer agent) within 14 days of initiation of study drug treatment

- Current enrollment in another clinical trial involving treatment and/or is receiving
an investigational agent for any reason

- Inability or unwillingness to comply with birth control requirements or regional
REMS/RevAid programs