NCT03798678

Brief Summary

This phase I trial studies the best dose of CB-839 HCl when given together with carfilzomib and dexamethasone in treating patients with multiple myeloma that has come back or does not respond to previous treatment. CB-839 HCl and carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving CB-839 HCl, carfilzomib, and dexamethasone may work better in treating patients with multiple myeloma.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
36

participants targeted

Target at P50-P75 for phase_1

Timeline
2mo left

Started Jul 2019

Longer than P75 for phase_1

Geographic Reach
1 country

5 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress98%
Jul 2019Jun 2026

First Submitted

Initial submission to the registry

January 9, 2019

Completed
1 day until next milestone

First Posted

Study publicly available on registry

January 10, 2019

Completed
6 months until next milestone

Study Start

First participant enrolled

July 8, 2019

Completed
7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2026

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2026

Last Updated

April 13, 2026

Status Verified

January 1, 2026

Enrollment Period

7 years

First QC Date

January 9, 2019

Last Update Submit

April 9, 2026

Conditions

Refractory Multiple MyelomaRecurrent Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

  • Maximum tolerated dose (MTD) and recommended phase II dose (RP2D)

    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.

    Up to 28 days

Secondary Outcomes (2)

  • Incidence of adverse events

    Up to 30 days after study treatment

  • Overall response rate (ORR)

    Up to 1 year

Other Outcomes (1)

  • Pharmacokinetic (PK) profiles and pharmacodynamic effect

    Days 1 and 15 of cycle 1

Study Arms (1)

Treatment (CB-839 HCI, dexamethasone, carfilzomib)

EXPERIMENTAL

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: CarfilzomibDrug: DexamethasoneDrug: Telaglenastat Hydrochloride

Interventions

CarfilzomibDRUG

Given IV

Also known as: Carfilnat, CFZ, Kyprolis, PR 171, PR-171, PR171
Treatment (CB-839 HCI, dexamethasone, carfilzomib)
DexamethasoneDRUG

Given PO

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, 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, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Dxevo, Fluorodelta, Fortecortin, Gammacorten, Hemady, Hexadecadrol, Hexadrol, LenaDex, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex
Treatment (CB-839 HCI, dexamethasone, carfilzomib)
Telaglenastat HydrochlorideDRUG

Given PO

Also known as: CB-839 HCl, Glutaminase Inhibitor CB-839 Hydrochloride
Treatment (CB-839 HCI, dexamethasone, carfilzomib)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients must have relapsed and/or refractory myeloma and be experiencing disease relapse
  • Patients must have measurable disease by International Myeloma Working Group (IMWG) criteria (any of the following):
  • Serum M-protein \>= 0.5 g/dL or for IgA myeloma, an elevated IgA level by quantitative IgA nephelometry
  • Urine M-protein \>= 200 mg in a 24-hour collection
  • Serum free light chain level \>= 10 mg/dL with an abnormal free light chain ratio
  • Measurable plasmacytoma by cross sectional imaging (computed tomography \[CT\], magnetic resonance imaging \[MRI\] or \[18F\]-fluorodeoxyglucose positron emission tomography with CT \[FDG PET/CT\])
  • % or more light chain restricted, clonal plasma cells in the bone marrow
  • At least two prior lines of therapy and all patients should have at least been exposed to a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 antibody
  • Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
  • Leukocytes \>= 3,000/mcL
  • Absolute neutrophil count \>= 1,000 cells/mm3 without growth factors (within 14 days of enrollment)
  • Hemoglobin \>= 8 g/dL (within 14 days of enrollment)
  • Platelets \>= 50,000 cells/mm3 (\>= 30,000 cells/mm3 if bone marrow plasma cells \>= 50% at enrollment)
  • Total bilirubin =\< 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional ULN
  • +5 more criteria

You may not qualify if:

  • Patients who are refractory or intolerant to carfilzomib (prior carfilzomib exposure accepted)
  • Patients who have received recent prior chemotherapy with:
  • Alkylators (e.g., melphalan, cyclophosphamide) and anthracyclines =\< 14 days prior to registration,
  • High dose corticosteroids and immunomodulatory drugs (thalidomide or lenalidomide) =\< 7 days prior to registration, or
  • Monoclonal antibodies =\< 14 days prior to registration
  • Patients who have not recovered from adverse events (AEs) due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1 except peripheral neuropathy)
  • Patients who are receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to CB-839 HCl, carfilzomib, or dexamethasone
  • Patients with uncontrolled intercurrent illness
  • Any of the following:
  • Pregnant women or women of reproductive ability who are unwilling to use two effective methods of contraception from the time of signing the informed consent form through 4 months after the last dose of study drug
  • Nursing women
  • And men who are unwilling to use birth control while taking the drug and for 4 months after stopping treatment
  • Pregnant women are excluded from this study because carfilzomib is a PI with the potential for abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with CB-839 HCl, carfilzomib, and dexamethasone, breastfeeding should be discontinued if the mother is treated with this drug combination
  • Adverse cardiac history (unstable angina, myocardial infarction less than 4 months, New York Heart Association \[NYHA\] class III or IV congestive heart failure \[CHF\], ejection fraction \[EF\] \< 40%, uncontrolled arrhythmias)
  • +11 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Yale University

New Haven, Connecticut, 06520, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomibDexamethasoneCalcium Dobesilateauricularumdexamethasone acetatedexamethasone 21-phosphate

Condition Hierarchy (Ancestors)

Neoplasms, Plasma CellNeoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

PregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsSteroids, FluorinatedBenzenesulfonatesBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsArylsulfonatesArylsulfonic AcidsSulfonic AcidsSulfur AcidsSulfur Compounds

Study Officials

  • Wilson I Gonsalves

    Mayo Clinic Cancer Center LAO

    PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

First Submitted

January 9, 2019

First Posted

January 10, 2019

Study Start

July 8, 2019

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

June 30, 2026

Last Updated

April 13, 2026

Record last verified: 2026-01

Locations

US(5)