Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

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

Protocol: OSU-15004

Full Title

A Phase Ib Trial of AR-42 with Pomalidomide in Relapsed Multiple Myeloma

Purpose

This phase Ib trial studies the side effects and best dose of histone deacetylase (HDAC) inhibitor AR-42 (AR-42) when given together with pomalidomide in treating patients with multiple myeloma that has returned after a period of improvement. HDAC inhibitor AR-42 may work to stop cancer growth by blocking an enzyme needed for cell growth. Pomalidomide is a drug used in chemotherapy that works to stop the growth of cancer cells by causing them to die. Giving HDAC inhibitor AR-42 together with pomalidomide may cause patients to respond better to treatment.

Study Objective

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.

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.

Are you eligible?

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 a 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

Prior exposure to pomalidomide or HDAC inhibitors is allowed

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 two negative serum or urine pregnancy tests 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 for 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 findings of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical grading 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

Multiple Myeloma