SX-682 in Combination With Carfilzomib, Daratumumab-Hyaluronidase, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

Trial Title: SX-682 in Combination With Carfilzomib, Daratumumab-Hyaluronidase, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

NCT ID: NCT06622005

Condition: Recurrent Multiple Myeloma
Refractory Multiple Myeloma

Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Dexamethasone
Daratumumab
Antibodies, Monoclonal

Study type: Interventional

Study phase: Phase 1

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Cxcr1/2 Inhibitor SX-682
Description: Given PO
Arm group label: Treatment

Other name: SX-682

Intervention type: Drug
Intervention name: Daratumumab and Recombinant Human Hyaluronidase
Description: Given SC
Arm group label: Treatment

Other name: Daratumumab and hyaluronidase

Intervention type: Drug
Intervention name: Carfilzomib
Description: Given IV
Arm group label: Treatment

Other name: CFZ

Other name: PR 171

Intervention type: Drug
Intervention name: Dexamethasone
Description: Given PO
Arm group label: Treatment

Other name: Adexone

Other name: Baycadron

Other name: Cortidexason

Other name: Decadrol

Other name: Fluorodelta

Other name: Loverine

Intervention type: Procedure
Intervention name: Biospecimen Collection
Description: Undergo Blood sample collection
Arm group label: Treatment

Intervention type: Procedure
Intervention name: Bone Marrow Aspiration
Description: Undergo Bone Marrow Aspiration
Arm group label: Treatment

Intervention type: Procedure
Intervention name: Echocardiography
Description: Undergo ECHO
Arm group label: Treatment

Other name: EC

Intervention type: Procedure
Intervention name: Positron Emission Tomography
Description: Undergo PET/CT
Arm group label: Treatment

Other name: PET

Other name: PET Scan

Intervention type: Procedure
Intervention name: Computed Tomography
Description: Undergo PET/CT
Arm group label: Treatment

Other name: CAT Scan

Intervention type: Procedure
Intervention name: Magnetic Resonance Imaging
Description: Undergo MRI
Arm group label: Treatment

Other name: MRI Scan

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

Criteria for eligibility:
Criteria:
Inclusion Criteria: - 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 - Estimated creatinine clearance ≥ 30 mL/min (Cockroft-Gault) - Left ventricular ejection fraction of at least 50% - Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and for 6 months following the last dose of the investigational drug. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately - Participant must understand the investigational nature of this study and sign an Independent ethics committee/institutional review board approved written informed consent form prior to receiving any study related procedure Exclusion Criteria: - 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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Start date: November 1, 2024

Completion date: November 1, 2029

Lead sponsor:
Agency: Roswell Park Cancer Institute
Agency class: Other

Source: Roswell Park Cancer Institute

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06622005