NCT06622005

Brief Summary

This phase I trial tests the safety and side effects of SX-682 in combination with standard of care treatment carfilzomib, daratumumab-hyaluronidase, and dexamethasone in treating patients with multiple myeloma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). SX-682 works by blocking certain sites on cells that suppress the ability of the immune system to destroy tumor cells. Blocking those specific sites allows other cells of the immune system to become "free" to kill tumor cells. Carfilzomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Daratumumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD38, which is found on some types of immune cells and tumor cells, including myeloma cells. Daratumumab may block CD38 and help the immune system kill tumor cells, while hyaluronidase helps to deliver daratumumab to CD38-expressing tumor cells through a subcutaneous injection. Dexamethasone is in a class of medications called corticosteroids. It is known to kill myeloma cells and is also used to reduce inflammation and lower the body's immune response to monoclonal antibodies like dratumumab and help lessen its side effects. Giving SX-682 in combination with carfilzomib, daratumumab-hyaluronidase and dexamethasone may be safe and tolerable in treating patients with relapsed or refractory multiple myeloma

Trial Health

77
On Track

Trial Health Score

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

Enrollment
15

participants targeted

Target at below P25 for phase_1

Timeline
48mo left

Started Apr 2025

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
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 Progress21%
Apr 2025Apr 2030

First Submitted

Initial submission to the registry

September 30, 2024

Completed
1 day until next milestone

First Posted

Study publicly available on registry

October 1, 2024

Completed
6 months until next milestone

Study Start

First participant enrolled

April 10, 2025

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 10, 2027

Expected
3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

April 10, 2030

Last Updated

April 21, 2026

Status Verified

April 1, 2026

Enrollment Period

2 years

First QC Date

September 30, 2024

Last Update Submit

April 16, 2026

Conditions

Outcome Measures

Primary Outcomes (1)

  • Incidence of dose-limiting toxicity

    Dose limiting toxicities will be summarized using frequencies and relative frequencies. Estimates of the dose-limiting toxicity rates will be obtained with 90% credible regions obtained by Jeffrey's prior method. The summary will be performed by dose level, if applicable.

    WIthin the first 28 days of start of treatment

Secondary Outcomes (4)

  • Percentage of Overall response rate

    Up to 3 years after last patient is enrollled

  • Percentage of Progression-free survival

    Up to 3 years after last patient is enrolled

  • Percentage of Overall Survival

    Up to 3 years after last patient is enrolled

  • Incidence of Adverse Events (AE's_

    Within the first 6 months of treatment

Study Arms (1)

Treatment

EXPERIMENTAL

Patients receive SX-682 PO BID on days 1-21 of each cycle. Patients also receive daratumumab-hyaluronidase SC once weekly on cycles 1 and 2 and once every 2 weeks on cycles 3-6 and carfilzomib IV on days 1, 8 and 15 and dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with sustained response after 6 cycles may continue to receive SX-682 PO BID on days 1-21, daratumumab-hyaluronidase SC on day 1, carfilzomib IV on days 1, 8, and 15 and dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, BM aspiration, ECHO and PET/CT or MRI on study.

Drug: Cxcr1/2 Inhibitor SX-682Drug: Daratumumab and Recombinant Human HyaluronidaseDrug: CarfilzomibDrug: DexamethasoneProcedure: Biospecimen CollectionProcedure: Bone Marrow AspirationProcedure: EchocardiographyProcedure: Positron Emission TomographyProcedure: Computed TomographyProcedure: Magnetic Resonance Imaging

Interventions

Given PO

Also known as: SX-682
Treatment

Given SC

Also known as: Daratumumab and hyaluronidase
Treatment

Given IV

Also known as: CFZ, PR 171
Treatment

Given PO

Also known as: Adexone, Baycadron, Cortidexason, Decadrol, Fluorodelta, Loverine
Treatment

Undergo ECHO

Also known as: EC
Treatment

Undergo Blood sample collection

Treatment

Undergo Bone Marrow Aspiration

Treatment

Undergo PET/CT

Also known as: PET, PET Scan
Treatment

Undergo PET/CT

Also known as: CAT Scan
Treatment

Undergo MRI

Also known as: MRI Scan
Treatment

Eligibility Criteria

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

You may qualify if:

  • Confirmed relapsed/ refractory multiple myeloma
  • Measurable disease including at least one of the following criteria:
  • Serum M-protein ≥ 0.5 g/dL
  • Urine M-protein ≥ 200 mg/24h
  • Serum free light chain assay: involved free light chain (FLC) level greater or equal to 100 mg/L provided serum free light chain ratio is abnormal
  • Bone marrow plasma cells ≥ 10% total bone marrow cells
  • ≥ 1 prior line of therapy
  • Planned treatment with a carfilzomib/daratumumab/dexamethasone regimen
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Absolute neutrophil count: ≥ 3 x 10\^9/L
  • Platelets: ≥ 75 x 10\^9/L
  • Hemoglobin: ≥ 7 g/dL
  • Total bilirubin: ≤ 1.5 x upper limit of normal (ULN): ≤ 3.0 x ULN for Gilbert's syndrome
  • Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\]) / alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]): ≤ 3 x ULN
  • Renal Function: Estimated creatinine clearance ≥ 45 mL/min (Cockroft-Gault)
  • +3 more criteria

You may not qualify if:

  • Patients with non-secretory myeloma, systemic light chain amyloidosis or, plasmacytoma
  • Intolerance to SX-682 or any other of the treatment components
  • Refractory to prior carfilzomib (i.e. relapse or progression on or within 60 days after completion of treatment)
  • Refractory to prior daratumumab (i.e. relapse or progression on or within 60 days after completion of treatment)
  • Concomitant medication(s) known to be (a) a strong inhibitor or inducer of CYP3A4, or (b) QT prolonging as defined in the drug's approved label, with the exception of drugs that are considered absolutely essential for the care of the subject or if the investigator believes that beginning therapy with such medication is vital to an individual subject's care while on study, and in either case, there is no alternative medication
  • Electrocardiogram (ECG) demonstrating a corrected QT (QTc) interval \> 470 msec or patients with congenital long QT syndrome
  • Coronary artery bypass, angioplasty, vascular stent, myocardial infarction, angina or congestive heart failure in the last 6 months
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, class III or IV heart failure (New York Heart Association functional classification system) or psychiatric illness/social situations that would limit compliance with study requirements
  • History of hepatitis B, C or HIV
  • Known active bacillus tuberculosis infection
  • Pregnant or nursing female participants
  • Unwilling or unable to follow protocol requirements
  • Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumabHyaluronoglucosaminidasecarfilzomibDexamethasoneCalcium DobesilateMagnetic Resonance Spectroscopy

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)

Glycoside HydrolasesHydrolasesEnzymesEnzymes and CoenzymesPolysaccharide-LyasesCarbon-Oxygen LyasesLyasesPregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsSteroids, FluorinatedBenzenesulfonatesBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsArylsulfonatesArylsulfonic AcidsSulfonic AcidsSulfur AcidsSulfur CompoundsSpectrum AnalysisChemistry Techniques, AnalyticalInvestigative Techniques

Study Officials

  • Jens Hillengass, MD

    Roswell Park

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

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

Study Record Dates

First Submitted

September 30, 2024

First Posted

October 1, 2024

Study Start

April 10, 2025

Primary Completion (Estimated)

April 10, 2027

Study Completion (Estimated)

April 10, 2030

Last Updated

April 21, 2026

Record last verified: 2026-04

Locations