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 : November 15, 2019
|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|
I. To determine the maximum tolerated dose, safety and efficacy of AR-42 in combination with pomalidomide in relapsed multiple myeloma (MM) patients.
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||72 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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 :||December 31, 2019|
|Estimated Study Completion Date :||December 31, 2019|
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: HDAC Inhibitor AR-42
Other: Laboratory Biomarker Analysis
- 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.
- 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.
- 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 ]
- 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.
- 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.
- 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.
- 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.
- 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.
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
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Yvonne Efebera, MD||Ohio State University Comprehensive Cancer Center|