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

NCT02569320 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: OSU-15004NCI-2015-01557PO-CL-MM-PI-003687
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot phase I 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.

Conditions

Recurrent Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (1)

• 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

  In the scenario where the MTD does not follow the assumption of non-decreasing toxicity of dose in both directions of the agent dose combinations, the MTD will be estimated by a bivariate isotonic estimator.

  21 days

Secondary Outcomes (7)

• Change in biomarker levels

  Baseline to up to 30 days after completion of study treatment

• Clinical benefit, defined as the proportion of patients experiencing complete response, very good partial response, or partial response

  Up to 30 days after completion of study treatment

• Duration of response

  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

• Incidence of toxicity, evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4 standard toxicity grading

  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

  Up to 30 days after completion of study treatment

Study Arms (1)

Treatment (pomalidomide, dexamethasone, HDAC inhibitor AR-42)

EXPERIMENTAL

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

Drug: Dexamethasone; Drug: HDAC Inhibitor AR-42; Other: Laboratory Biomarker Analysis; Drug: Pomalidomide

Interventions

Dexamethasone DRUG

Given PO

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, Visumetazone

Treatment (pomalidomide, dexamethasone, HDAC inhibitor AR-42)

HDAC Inhibitor AR-42 DRUG

Given PO

Also known as: AR-42, HDAC-42, OSU-HDAC42

Treatment (pomalidomide, dexamethasone, HDAC inhibitor AR-42)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pomalidomide, dexamethasone, HDAC inhibitor AR-42)

Pomalidomide DRUG

Given PO

Also known as: 4-Aminothalidomide, Actimid, CC-4047, Pomalyst

Treatment (pomalidomide, dexamethasone, HDAC inhibitor AR-42)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ohio State University Comprehensive Cancer Center: lead
• Celgene: collaborator

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• Cheng H, Xie Z, Jones WP, Wei XT, Liu Z, Wang D, Kulp SK, Wang J, Coss CC, Chen CS, Marcucci G, Garzon R, Covey JM, Phelps MA, Chan KK. Preclinical Pharmacokinetics Study of R- and S-Enantiomers of the Histone Deacetylase Inhibitor, AR-42 (NSC 731438), in Rodents. AAPS J. 2016 May;18(3):737-45. doi: 10.1208/s12248-016-9876-3. Epub 2016 Mar 4.

  PMID: 26943915 DERIVED

Related Links

• The Jamesline

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; HDAC-42; pomalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Yvonne Efebera, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2015
• First Posted: October 6, 2015
• Study Start: May 20, 2016
• Primary Completion: November 14, 2020
• Study Completion: March 10, 2021
• Last Updated: June 15, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)