Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02569320
Recruitment Status : Suspended (Internal data analysis)
First Posted : October 6, 2015
Last Update Posted : July 18, 2018
Sponsor:
Collaborator:
Celgene
Information provided by (Responsible Party):
Yvonne Efebera, Ohio State University Comprehensive Cancer Center

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.

Condition or disease Intervention/treatment Phase
Recurrent Plasma Cell Myeloma Drug: Dexamethasone Drug: HDAC Inhibitor AR-42 Other: Laboratory Biomarker Analysis Drug: Pomalidomide Phase 1

Detailed Description:

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Trial of AR-42 With Pomalidomide in Relapsed Multiple Myeloma
Actual Study Start Date : May 9, 2016
Estimated Primary Completion Date : March 31, 2019
Estimated Study Completion Date : March 31, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Treatment (pomalidomide, dexamethasone, HDAC inhibitor AR-42)
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
Given PO
Other Names:
  • 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

Drug: HDAC Inhibitor AR-42
Given PO
Other Names:
  • AR-42
  • HDAC-42
  • OSU-HDAC42

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Pomalidomide
Given PO
Other Names:
  • 4-Aminothalidomide
  • Actimid
  • CC-4047
  • Pomalyst




Primary Outcome Measures :
  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 [ Time Frame: 21 days ]
    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.


Secondary Outcome Measures :
  1. Change in biomarker levels [ Time Frame: Baseline to up to 30 days after completion of study treatment ]
    Summary statistics will be computed for baseline biomarkers. The absolute and percent change from baseline will be calculated for each subsequent measurement. Summary statistics will be computed for each collection time point.

  2. 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 ]
  3. 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 ]
    Evaluated using the methods of Kaplan and Meier, with a focus on graphical evaluation as well as early timepoint and median estimates of survival distributions.

  4. 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 ]
    Frequency distributions and other descriptive measures will form the basis of analysis of toxicity number and severity. Adverse events will be summarized by CTCAE v.4 category and perceived causal relationship to the study therapy. Tolerability will also be determined through assessing the number of patients who required dose modifications and/or dose delays in subsequent cycles. In addition, the proportion of patients who go off treatment due to adverse reactions or those who refuse further treatment for lesser toxicities that inhibit their willingness to continue on trial will be captured.

  5. 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 ]
    The number and percentage of patients experiencing objective response will be descriptively summarized overall and by dose level. The objective response rate will be analyzed by using a 95% confidence interval for the proportion responding at trial closure in the treated population.

  6. 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 ]
    Evaluated using the methods of Kaplan and Meier, with a focus on graphical evaluation as well as early timepoint and median estimates of survival distributions.

  7. 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 ]
    Evaluated using the methods of Kaplan and Meier, with a focus on graphical evaluation as well as early timepoint and median estimates of survival distributions.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02569320


Locations
Layout table for location information
United States, Ohio
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Yvonne Efebera
Celgene
Investigators
Layout table for investigator information
Principal Investigator: Yvonne Efebera, MD Ohio State University Comprehensive Cancer Center

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Yvonne Efebera, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT02569320     History of Changes
Other Study ID Numbers: OSU-15004
NCI-2015-01557 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
PO-CL-MM-PI-003687
First Posted: October 6, 2015    Key Record Dates
Last Update Posted: July 18, 2018
Last Verified: July 2018

Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Dexamethasone acetate
Pomalidomide
Thalidomide
BB 1101
Histone Deacetylase Inhibitors
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal