HDAC Inhibitor AR-42 and Pomalidomide in Treating Patients With Relapsed Multiple Myeloma

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose, safety and efficacy of AR-42 in combination with
pomalidomide in relapsed multiple myeloma (MM) patients.

SECONDARY OBJECTIVES:

I. To determine time to progression (TTP). II. To determine overall survival (OS).

OUTLINE: This is a dose-escalation study of HDAC inhibitor AR-42 and pomalidomide.

Patients receive pomalidomide orally (PO) daily on days 1-21, dexamethasone PO twice weekly
(BIW) or thrice weekly (TIW) weeks 1-3, and HDAC inhibitor AR-42 PO BIW or TIW on weeks 1-3.
Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for at least 30 days.

Inclusion Criteria:

- Patients with measurable disease as defined by any of the following:

- Serum M-protein >= 0.5 g/dl (>= 500 mg/dL)

- Urine monoclonal protein >= 200 mg/24h

- Involved free light chain (FLC) level >= 10 mg/dl (>= 100 mg/l) and an abnormal
serum free light chain ratio (< 0.26, or > 1.65)

- Patients must have previously received Lenalidomide and proteasome inhibitor.

- Patients must be lenalidomide failures: disease progression on a prior
lenalidomide-based therapy or progression within 60 days of the last dose of a
lenalidomide; patients should have received at least 2 cycles of a lenalidomide-based
regimen at standard doses to be evaluable for refractoriness; prior intolerance to
lenalidomide does not exclude participation in the study except in cases of severe
allergic reaction

- Prior radiation is permitted; however, at least 2 weeks must have elapsed since the
completion of therapy and patients must have recovered from all therapy-associated
toxicities to no greater than grade 1 at the time of registration; patients with
symptomatic disease may receive palliative corticosteroids up to 1 week before
initiating therapy

- Patient must have received 2 or more prior lines of systemic therapy for myeloma;
patients must be off last treatment for at least 2 weeks (wks) by the beginning of
treatment on this protocol

- Patients must have a Karnofsky performance score of 50% or greater

- Patients must have absolute neutrophil count (ANC) > 1000/uL

- Platelets >= 75,000/uL

- Total bilirubin =< 1.5 mg/dL

- Alkaline phosphatase =< 4 x institutional upper limit of normal (IULN)

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x IULN

- Patients must have a serum creatinine limit of ≤1.5 ULN or creatinine clearance of ≥60
ml/min measured within 14 days of registration.

- All study participants must be registered into the mandatory POMALYST (pomalidomide)
Risk Evaluation and Mitigation Strategy (REMS) program, and be willing and able to
comply with the requirements of the POMALYST REMS program

- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
test with a sensitivity of at least 50 mIU/mL prior to starting therapy and prior to
beginning another cycle (if applicable); women of child-bearing potential and men must
agree to use adequate contraception (hormonal or barrier method of birth control;
abstinence) prior to study entry and for the duration of study participation; should a
woman become pregnant or suspect she is pregnant while she or her partner is
participating in this study, she should inform her treating physician immediately; a
female of childbearing potential (FCBP) is a sexually mature woman who: 1) has not
undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally
postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in
the preceding 24 consecutive months)

- The patient must be willing to comply with fertility requirements as below:

- Male patients must agree to use an adequate method of contraception for the
duration of the study and for 28 days afterwards

- Female patients must be either postmenopausal, free from menses >= 2 yrs,
surgically sterilized, willing to use two adequate barrier methods of
contraception to prevent pregnancy, or agree to abstain from heterosexual
activity starting with screening (4 weeks prior to initiating treatment) and 28
days after treatment, per POMALYST REMS™ program

- Patients must agree not to donate blood, sperm/ova during the course of taking
protocol therapy and for at least 4 weeks after stopping treatment

Exclusion Criteria:

- History of severe allergic reaction, including erythema nodosum, to lenalidomide

- Patients unable to receive adequate thromboprophylaxis in combination with
pomalidomide

- Patients who have received investigational agents within 2 weeks or within 5
half-lives of the agent and active metabolites (whichever is longer) and who have not
recovered from side effects of those therapies

- Patients with a mean QT interval corrected by Bazett's formula (QTcB) > 450 msec in
males and > 470 msec in females

- Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C

- Patients with active (untreated or relapsed) central nervous system (CNS) metastasis
of the patient's myeloma

- Any other medical condition, including mental illness or substance abuse, deemed by
the investigator(s) to likely interfere with the patient's ability to sign informed
consent, cooperate and participate in the study, or interfere with the interpretation
of the results

- Patients with a prior history of malignancies, other than multiple myeloma, are
excluded unless the subject has been free of the disease for ≥ 5 years with the
exception of the following non-invasive malignancies:

- Basal cell carcinoma of the skin

- Squamous cell carcinoma of the skin

- Carcinoma in situ of the cervix

- Carcinoma in situ of the breast

- Incidental histological finding of prostate cancer (T1a or T1b using the TNM
[tumor, nodes, metastasis] clinical staging system) or prostate cancer that is
curative.

- Patients with malabsorption or any other condition that in the opinion of the
principal investigator could cause difficulty in absorption of drug

- Patients that have previously progressed on pomalidomide treatment.