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

• Register: ClinicalTrials.gov
• Last refreshed on: 21 June 2021
• Main ID: NCT02569320
• Date of registration: 03/10/2015
• Prospective Registration: Yes
• Primary sponsor: Ohio State University Comprehensive Cancer Center
• Public title: HDAC Inhibitor AR-42 and Pomalidomide in Treating Patients With Relapsed Multiple Myeloma
• Scientific title: A Phase 1b Trial of AR-42 With Pomalidomide in Relapsed Multiple Myeloma
• Date of first enrolment: May 20, 2016
• Target sample size: 9
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02569320
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Yvonne Efebera, MD
• Affiliation: Ohio State University Comprehensive Cancer Center

Key inclusion & exclusion criteria

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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Recurrent Plasma Cell Myeloma

Intervention(s)

Drug: HDAC Inhibitor AR-42

Drug: Pomalidomide

Drug: Dexamethasone

Other: Laboratory Biomarker Analysis

Primary Outcome(s)

Maximum tolerated dose (MTD) of HDAC inhibitor AR-42 in combination with pomalidomide, defined as the highest dose level at which less than 20% of patients experience a dose-limiting toxicity [Time Frame: 21 days]

Secondary Outcome(s)

Clinical benefit, defined as the proportion of patients experiencing complete response, very good partial response, or partial response [Time Frame: Up to 30 days after completion of study treatment]

Change in biomarker levels [Time Frame: Baseline to up to 30 days after completion of study treatment]

Duration of response [Time Frame: From first observation of partial response to the time of disease progression (taking as a reference for progressive disease the smallest measurements recorded since treatment started), assessed up to 30 days after completion of study treatment]

Time to progression [Time Frame: From the start of the treatment until the criteria for disease progression are met, assessed up to 30 days after completion of study treatment]

Incidence of toxicity, evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4 standard toxicity grading [Time Frame: Up to 30 days after completion of study treatment]

Number of patients experiencing objective response, based on criteria adapted from the International Myeloma working Group Uniform Response Criteria [Time Frame: Up to 30 days after completion of study treatment]

Progression-free survival [Time Frame: From start of treatment to disease progression or death, regardless of cause of death, whichever comes first, assessed up to 30 days after completion of study treatment]

Secondary ID(s)

NCI-2015-01557

OSU-15004

PO-CL-MM-PI-003687

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Celgene