NCT05497804

Brief Summary

This phase II trial test whether combination chemotherapy works to improve blood test results in patients with high-risk multiple myeloma. Chemotherapy drugs, such as carfilzomib, daratumumab, lenalidomide, and 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. This trial may help determine if patients who have a small amount of cancer left after the initial treatment, called minimal residual disease, will benefit from the drug combination.

Trial Health

75
On Track

Trial Health Score

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

Enrollment
17

participants targeted

Target at below P25 for phase_2

Timeline
31mo left

Started Sep 2022

Longer than P75 for phase_2

Geographic Reach
1 country

3 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 Progress59%
Sep 2022Nov 2028

First Submitted

Initial submission to the registry

August 3, 2022

Completed
8 days until next milestone

First Posted

Study publicly available on registry

August 11, 2022

Completed
1 month until next milestone

Study Start

First participant enrolled

September 22, 2022

Completed
5.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 20, 2027

Expected
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

November 20, 2028

Last Updated

February 3, 2026

Status Verified

January 1, 2026

Enrollment Period

5.2 years

First QC Date

August 3, 2022

Last Update Submit

January 30, 2026

Conditions

Outcome Measures

Primary Outcomes (1)

  • Rate of sustained minimal residual disease (MRD) negativity

    MRD negative status at any point, with a repeated MRD negative status one year later. All subjects meeting the eligibility criteria who have signed a consent form and have begun treatment will be evaluable, with the exception of subjects determined to be a major violation.

    At 1 year

Secondary Outcomes (4)

  • Overall response rate (>= confirmed very good partial response ([VGPR])

    End of induction, end of consolidation, and every 3 cycles of maintenance, up to two years or 24. One cycle is 28 days. after treatmentmonths

  • Overall survival

    Up to 10 years

  • Progression-free survival

    Up to 10 years

  • Incidence of adverse events

    Up to 30 days after administration of study therapy

Other Outcomes (2)

  • Clonal architecture before treatment

    Before and after treatment, up to two years or 24 months

  • Bone marrow microenvironment

    Before and after treatment, up to two years or 24 months

Study Arms (1)

Treatment (combination chemotherapy)

EXPERIMENTAL

INDUCTION: Patients receive carfilzomib IV on days 2, 8, and 15 of cycle 1 and days 1, 8, and 15 of cycles 2-12, lenalidomide PO days 1-21 of each cycle, daratumumab SC days 1, 8, 15, and 22 of cycles 1 and 2, days 1 and 15 of cycles 3-6, and day 1 of subsequent cycles, and dexamethasone PO or IV on days 1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients receive carfilzomib IV on days 1, 8, and 15, lenalidomide PO days 1-21, daratumumab SC day 1 of each cycle. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive carfilzomib IV on day 1, lenalidomide PO days 1-21, daratumumab day 1 of each cycle. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspirate and biopsy, MRI and, CT/PET.

Procedure: Bone Marrow Aspiration and BiopsyDrug: CarfilzomibProcedure: Computed TomographyBiological: DaratumumabDrug: DexamethasoneDrug: LenalidomideProcedure: Magnetic Resonance ImagingProcedure: Positron Emission TomographyProcedure: Multigated Acquisition ScanProcedure: Biospecimen CollectionProcedure: EchocardiographyProcedure: Chest Radiography

Interventions

Undergo bone marrow aspiration and biopsy

Treatment (combination chemotherapy)

Given PO

Also known as: CC-5013, CC5013, CDC 501, Revlimid
Treatment (combination chemotherapy)

Undergo MRI

Also known as: Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging
Treatment (combination chemotherapy)

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging
Treatment (combination chemotherapy)

Undergo MUGA scan

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide ventriculography, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning
Treatment (combination chemotherapy)

Given IV/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, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex
Treatment (combination chemotherapy)

Given IV

Also known as: Kyprolis, PR-171
Treatment (combination chemotherapy)

Undergo CT or PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography
Treatment (combination chemotherapy)
DaratumumabBIOLOGICAL

Given SC

Also known as: Darzalex, HuMax-CD38, JNJ-54767414, Daratumumab Biosimilar HLX15, Daratumumab-fihj
Treatment (combination chemotherapy)

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection
Treatment (combination chemotherapy)

Undergo ECHO

Also known as: EC
Treatment (combination chemotherapy)

Undergo chest x-ray

Also known as: chest x-ray
Treatment (combination chemotherapy)

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age \>= 18 years and =\< 80 years.
  • Patient must have suspected or confirmed newly diagnosed multiple myeloma by International Myeloma Working Group (IMWG) criteria.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
  • Provide informed written consent.
  • Willing to return to enrolling institution for follow-up during the active treatment phase of the trial.
  • Willing to provide blood and bone marrow samples for planned research.
  • Life expectancy \> 6 months.
  • Able to take aspirin (325 mg) daily as prophylactic anticoagulation.
  • Note: subjects intolerant to aspirin may use warfarin, novel oral anticoagulants, or low dose molecular weight heparin.
  • Patients must have monoclonal protein studies (serum free light chain assay, serum immunofixation or serum matrix-assisted laser desorption ionization time-of-flight mass-spectrometry \[MASS-FIX\]) at time of diagnosis before induction therapy initiated and available for review to be enrolled. Note: Patients are allowed to participate in this study if urine electrophoresis immunofixation study was not done at time of diagnosis or cannot be obtained
  • High risk myeloma, which is untreated, defined as any two of:
  • Beta-2 microglobulin \>5.5
  • Gain or amplification of chr1q
  • del17p or monosomy 17 or TP53 mutation (if known)
  • t(4;14) or t(14;16)
  • +12 more criteria

You may not qualify if:

  • Monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma, light chain amyloidosis with organ involvement.
  • Diagnosed or treated for another malignancy =\< 1 year prior to pre- registration or previously diagnosed with another malignancy and have any evidence of residual disease.
  • NOTE: Subjects with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
  • Other co-morbidity which would interfere with subject's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease.
  • Other concurrent chemotherapy, or any ancillary therapy considered investigational. NOTE: Concurrent chemotherapy is any treatment not related to multiple myeloma.
  • NOTE: Concurrent chemotherapy is any treatment not related to multiple myeloma
  • NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment.
  • Peripheral neuropathy \>= grade 3 on clinical examination or grade 2 with pain =\< 30 days prior to registration.
  • Major surgery =\< 14 days prior to pre-registration.
  • Any medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
  • Known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to respective package inserts or investigator's brochure) or known sensitivity to mammalian-derived products. Known allergies, hypersensitivity, or intolerance to trial drugs.
  • Inability to comply with protocol/procedures.
  • Received prior treatment for multiple myeloma prior to pre-registration. Note: results can still be pending as long as the tests have been performed
  • If any of the following exist at screening, subject will not be eligible for trial because this trial involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
  • Pregnant women
  • +9 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

MeSH Terms

Conditions

Multiple Myeloma

Interventions

BiopsycarfilzomibdaratumumabDexamethasoneCalcium Dobesilateauricularumdexamethasone acetatedexamethasone 21-phosphateLenalidomideMagnetic Resonance SpectroscopySpecimen HandlingX-Rays

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)

CytodiagnosisCytological TechniquesClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisDiagnostic Techniques, SurgicalSurgical Procedures, OperativeInvestigative TechniquesPregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsSteroids, FluorinatedBenzenesulfonatesBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsArylsulfonatesArylsulfonic AcidsSulfonic AcidsSulfur AcidsSulfur CompoundsPhthalimidesPhthalic AcidsAcids, CarbocyclicCarboxylic AcidsPiperidonesPiperidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsIsoindolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingSpectrum AnalysisChemistry Techniques, AnalyticalElectromagnetic RadiationElectromagnetic PhenomenaMagnetic PhenomenaPhysical PhenomenaRadiationRadiation, Ionizing

Study Officials

  • Shaji K. Kumar, MD

    Mayo Clinic in Rochester

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 3, 2022

First Posted

August 11, 2022

Study Start

September 22, 2022

Primary Completion (Estimated)

November 20, 2027

Study Completion (Estimated)

November 20, 2028

Last Updated

February 3, 2026

Record last verified: 2026-01

Locations