CB-839 HCl in Combination With Carfilzomib and Dexamethasone in Treating Patients With Recurrent or Refractory 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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03798678|
Recruitment Status : Recruiting
First Posted : January 10, 2019
Last Update Posted : January 10, 2019
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Plasma Cell Myeloma Refractory Plasma Cell Myeloma||Drug: Carfilzomib Drug: Dexamethasone Drug: Glutaminase Inhibitor CB-839 Hydrochloride||Phase 1|
I. To determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of glutaminase inhibitor CB-839 hydrochloride (CB-839 HCl) in combination with carfilzomib and dexamethasone.
I. Evaluate the safety and tolerability of CB-839 HCl in combination with carfilzomib and dexamethasone.
II. To determine the overall response rate (ORR) associated with the combination of CB-839 HCl with carfilzomib and dexamethasone.
CORRELATIVE RESEARCH OBJECTIVES:
I. Evaluate plasma pharmacokinetic (PK) profiles of CB-839 HCl and carfilzomib when used in combination.
II. To perform molecular profiling assays on malignant and normal tissues, including, but not limited to, whole exome sequencing (WES), messenger ribonucleic acid (RNA) sequencing (RNAseq), circulating cell free (cf) deoxyribonucleic acid (DNA) analysis, flow cytometry assessments, immunohistochemical (IHC) staining, and metabolomics-based assessments in order to identify potential predictive and prognostic biomarkers, and identify resistance mechanisms using genomic DNA, RNA, flow cytometry, IHC, and metabolomics-based assessment platforms.
III. To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research.
IV. To bank CD138+ multiple myeloma (MM) cells from the bone marrow, and blood (for cfDNA analysis) obtained from patients at the Experimental Therapeutics Clinical Trials Network (ETCTN) Biorepository at Nationwide Children's Hospital.
OUTLINE: This is a dose escalation study of glutaminase inhibitor CB-839 hydrochloride.
Patients receive glutaminase inhibitor CB-839 hydrochloride orally (PO) every 12 hours on days 1-28, dexamethasone PO on days 1, 2, 8, 9, 15, 16, and 23, and carfilzomib intravenously (IV) over 10 minutes on days 1, 2, 8, 9, 15, and 16. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then periodically for up to 1 year.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Dose-Escalation and Dose-Expansion Trial of a Novel Glutaminase Inhibitor (CB-839 HCl) in Combination With Carfilzomib and Dexamethasone in Relapsed and/or Refractory Multiple Myeloma|
|Actual Study Start Date :||December 26, 2018|
|Estimated Primary Completion Date :||January 30, 2022|
|Estimated Study Completion Date :||January 30, 2022|
Experimental: Treatment (CB-839 HCI, dexamethasone, carfilzomib)
Patients receive glutaminase inhibitor CB-839 Patients receive glutaminase inhibitor CB-839 hydrochloride PO every 12 hours on days 1-28, dexamethasone PO on days 1, 2, 8, 9, 15, 16, and 23, and carfilzomib IV over 10 minutes on days 1, 2, 8, 9, 15, and 16. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity
Drug: Glutaminase Inhibitor CB-839 Hydrochloride
Other Name: CB-839 HCl
- Maximum tolerated dose (MTD) and recommended phase II dose (RP2D) [ Time Frame: Up to 28 days ]MTD will be determined by dose limiting toxicity (DLT). MTD is defined as the dose level below the lowest dose that induces DLT in at least 2 patients (out of 6). The highest dose is defined as the RP2D. A standard cohort 3+3 design will be used.
- Incidence of adverse events [ Time Frame: Up to 30 days after study treatment ]Incidence of adverse events will be graded according to Common Terminology Criteria for Adverse Events version 5.0. The number and severity of all AEs (overall and by dose-level) will be tabulated and summarized in this patient population. These data will be summarized with and without regard to the relationship to the treatment (i.e., ignoring the relationship data and after sub-setting the data to only events that are at least possibly related to study drug).
- Overall response rate (ORR) [ Time Frame: Up to 1 year ]The ORR will be defined as the percentage of patients that achieve at least a partial response (as their best response). Properties of the binomial distribution will be used in order to construct an exact 95% confidence interval around this proportion.
- Pharmacokinetic (PK) profiles and pharmacodynamic effect [ Time Frame: Days 1 and 15 of cycle 1 ]PK and pharmacodynamic data will be examined in an exploratory manner.
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): NCT03798678
|United States, Minnesota|
|Mayo Clinic Cancer Center LAO||Recruiting|
|Rochester, Minnesota, United States, 55905|
|Contact: Wilson I. Gonsalves email@example.com|
|Principal Investigator: Wilson I. Gonsalves|
|Principal Investigator:||Wilson Gonsalves||Mayo Clinic Cancer Center LAO|