Recurrent Multiple Myeloma, Refractory Multiple Myeloma
Conditions
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
Interventions
Given PO
Given SC
DRUGCarfilzomib
Given IV
DRUGDexamethasone
Given PO
PROCEDUREBiospecimen Collection
Undergo Blood sample collection
PROCEDUREBone Marrow Aspiration
Undergo Bone Marrow Aspiration
PROCEDUREEchocardiography
Undergo ECHO
PROCEDUREPositron Emission Tomography
Undergo PET/CT
PROCEDUREComputed Tomography
Undergo PET/CT
PROCEDUREMagnetic Resonance Imaging
Undergo MRI
Sponsors
Roswell Park Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 * Renal Function: Estimated creatinine clearance ≥ 45 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose-limiting toxicity | WIthin the first 28 days of start of treatment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Overall response rate | Up to 3 years after last patient is enrollled | Obtained using Jeffrey's prior method |
| Percentage of Progression-free survival | Up to 3 years after last patient is enrolled | Determined using Kaplan-Meier estimates |
| Percentage of Overall Survival | Up to 3 years after last patient is enrolled | Determined using Kaplan-Meier estimates |
| Incidence of Adverse Events (AE's_ | Within the first 6 months of treatment | AE's will be grading using CTCAE v.5. |
Countries
United States
Contacts
Primary ContactASK RPCI
Outcome results
None listed