Study of Selinexor With Carfilzomib, Isatuximab and Dexamethasone for Patients With Relapsed and/or Refractory Multiple Myeloma

NCT07479979 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: BTCRC-MM21-528
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this Phase Ib/II trial is to study the safety and tolerability of the combination of selinexor, carfilzomib, isatuximab-OBDS (on body delivery system) and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma, who have received at least one line of therapy. The phase Ib portion comprises the safety run-in with 6-12 patients, with the option to reduce the selinexor dose from 40 mg to 20 mg if the higher dose reaches the prescribed toxicity threshold. The Phase II portion of the trial will test the Recommended Phase 2 Dose (RP2D) in an expansion cohort of up to 50 patients.

Conditions

Relapse Multiple Myeloma; Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Adverse Events

  Adverse events will be assessed by evaluating Grade 3 and 4 toxicities as defined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.

  24 months

Secondary Outcomes (7)

• Progression-free Survival (PFS)

  24 months

• Overall Response Rate (ORR)

  24 months

• Minimal Residual Disease (MRD) Rate

  24 months

• Progression-free Survival (PFS) in subgroup population

  24 months

• Overall Response Rate (ORR) in subgroup population

  24 months

Study Arms (2)

Phase 1: Selinexor, Carfilzomib, Isatuximab, and Dexamethasone

EXPERIMENTAL

Participants will receive selinexor at their assigned dose taken orally on a 28-day cycle combined with carfilzomib, isatuximab, and dexamethasone IV administered on a 28-day cycle until disease progression or for an unacceptable toxicity.

Drug: Selinexor; Drug: Carfilzomib; Drug: Isatuximab; Device: Isatuximab SC Wearable Injection System; Drug: Dexamethasone

Phase 2: Selinexor, Carfilzomib, Isatuximab, and Dexamethasone

EXPERIMENTAL

Participants will receive selinexor at their assigned dose taken orally on a 28-day cycle combined with carfilzomib, isatuximab, and dexamethasone IV administered on a 28-day cycle until disease progression or for an unacceptable toxicity.

Drug: Selinexor; Drug: Carfilzomib; Drug: Isatuximab; Device: Isatuximab SC Wearable Injection System; Drug: Dexamethasone

Interventions

Selinexor DRUG

Phase I: Selinexor at assigned dose by mouth begin Day 1, 8, 15, and 22 until study treatment stop. - Dose Levels: -1: 20mg weekly 0 (Starting Dose): 40mg weekly 1: 60mg weekly Phase II: Selinexor at assigned dose by mouth based on the phase 1 findings. Selinexor will be taken weekly (Days 1, 8, 15, and 22).

Phase 1: Selinexor, Carfilzomib, Isatuximab, and Dexamethasone; Phase 2: Selinexor, Carfilzomib, Isatuximab, and Dexamethasone

Carfilzomib DRUG

Phase I and Phase II: Carfilzomib IV will be administered on Day 1, 8, and 15. The first dose of carfilzomib will be carfilzomib 20mg/m2 IV. Every dose after will be carfilzomib 56mg/m2.

Phase 1: Selinexor, Carfilzomib, Isatuximab, and Dexamethasone; Phase 2: Selinexor, Carfilzomib, Isatuximab, and Dexamethasone

Isatuximab DRUG

Phase I and Phase II: Isatuximab 1400mg will be administered by injection from the wearable device. For the first 28 days isatuximab will be administered on days 1, 8, 15, and 22. For every cycle after isatuximab will be administered on days 1 and 15.

Phase 1: Selinexor, Carfilzomib, Isatuximab, and Dexamethasone; Phase 2: Selinexor, Carfilzomib, Isatuximab, and Dexamethasone

Dexamethasone DRUG

Phase I and Phase II: Dexamethasone 40mg will be administered either by IV or orally on Days 1, 8, 15, and 22.

Phase 1: Selinexor, Carfilzomib, Isatuximab, and Dexamethasone; Phase 2: Selinexor, Carfilzomib, Isatuximab, and Dexamethasone

Isatuximab SC Wearable Injection System DEVICE

Phase I and Phase II: Isatuximab 1400mg will be administered by injection from the wearable device. For the first 28 days isatuximab will be administered on days 1, 8, 15, and 22. For every cycle after isatuximab will be administered on days 1 and 15.

Phase 1: Selinexor, Carfilzomib, Isatuximab, and Dexamethasone; Phase 2: Selinexor, Carfilzomib, Isatuximab, and Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of ≤2 within 28 days prior to registration. A performance status of \>2 will be allowed only if it is related to bone pain that is expected to improve with treatment.
• Patients with a diagnosis of relapsed or relapsed/refractory MM who have received at least 1 line of prior therapy. In the phase 2 component, we will specifically enrich for patients with 1q gain or amplification as well as other IMWG high-risk features with the aim of including ≥50% of the enrolled population (a minimum of 25 patients) with high risk disease. High risk disease is defined as the presence of:
• del(17p), with a cutoff of \>20% clonal fraction, and/or TP53 mutation
• an IgH translocation including t(4;14), t(14;16), or t(14;20) along with 1q+ and/or del(1p32)
• monoallelic del(1p32) along with 1q+ or biallelic del(1p32)
• β2 microglobulin ≥5.5 mg/L with normal creatinine (\<1.2 mg/dL) For purposes of the study, patients with 2 or more of these high risk cytogenetic abnormalities. Patients known to carry such abnormalities on previous FISH analysis and/or cytogenetic testing will also be eligible, if results from on-study marrow are unavailable or not obtainable. Therefore, enrollment of patients without these feature(s) will halt once 25 standard risk, non-mutated patients are enrolled and treated. Refractory is defined as patients relapsing on or within 60 days of therapy, per IMWG.
• Patients must have measurable disease as defined by at least one of the following:
• A monoclonal protein (M-protein): ≥ 0.5g/dL on serum protein electrophoresis or ≥ 200 mg of monoclonal protein on a 24-hour urine protein or involved serum light chain ≥ 10 mg/dl at time of relapse, or
• Biopsy proven plasmacytoma that can be assessed by physical exam or imaging, or
• If non- or oligo secretory, ≥10% plasma cells on BM biopsy/aspirate at time of relapse or plasmacytoma as described and/or evaluable disease by positron emission tomography, either MR or CT. Patients must be willing to undergo repeat BM aspirate and biopsy to assess response.
• Due to the difficulty of quantitation using conventional SPEP of IgA and IgD monoclonal proteins, an absolute increase of \> 25 % over previous nadir of the total values in mg/dl (or adjusted units) will meet eligibility requirements for progression and study eligibility.
• NOTE: Urine protein electrophoresis (UPEP) (on a 24-h collection) is required at baseline; no substitute method is acceptable. Urine must be assessed to establish response if the baseline urine M-spike is ≥ 200 mg/24 h. Please note that if both serum and urine M-components are present at the time of enrollment, both should be assessed in order to evaluate response for CR but monthly 24 hour urine tests outside of this response testing are not necessary. For patients without a monoclonal urine protein ≥200mg/24 hours, the test only needs to be repeated to corroborate CR.
• Patients may have received any number and type of previous treatments for myeloma including carfilzomib and an anti-CD38 antibody but cannot be refractory to the combination of daratumumab and carfilzomib.

You may not qualify if:

• Active infection requiring systemic therapy (Note: subjects can be enrolled if they will be completing antibiotic therapy by the time of actual start date of treatment)
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• Known additional malignancy that is active and/or progressive, requiring urgent or new treatment. Exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, prostate cancer on stable hormonal therapy, DCIS or other cancer for which the subject has been disease-free for at least three years. Patients who have undergone a curative procedure for another malignancy are eligible.
• Active central nervous system (CNS) metastases. NOTE: Subjects who are symptomatic and have not undergone prior brain imaging must undergo a head computed tomography (CT) scan or brain MRI within 28 days prior to registration to exclude brain metastases.
• History of severe hypersensitivity reaction (grade 3 or more) to an anti-CD38 antibody that in the opinion of the investigator excludes the use of these drugs.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (NYHA Class III and IV), unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Treatment with any investigational drug within 14 days prior to registration.
• Any previously active gastrointestinal dysfunction that prevents the patient from swallowing tablets or interferes with absorption of study treatment. This is likely to be a rare occurrence.
• Treatment with moderate or strong inhibitors/inducers of CYP3A within 7 days prior to Day 1 of Cycle 1. Potent inhibitors of CYP3A4 include clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, goldenseal and grapefruit. Inducers of CYP3A4 include phenobarbital, phenytoin, rifampicin, and St. John's Wort. For patients receiving diltiazem or verapamil, alternative therapy will need to be substituted, if necessary, if the drug cannot otherwise be safely discontinued.
• Currently receiving a strong CYP3A4 inhibitor/inducer and unable to discontinue such medications.
• Prior exposure to a SINE compound, including selinexor.
• Exposure to anti-CD38 directed therapy (ex. daratumumab; isatuximab; daratumumab/hyaluronidase) within 6 months of study registration.
• Patients with an echocardiogram or other cardiac imaging study showing a LVEF of \<40% within 60 days of study registration.
• Presence of plasma cell leukemia at time of registration
• Patients with a history of POEMS syndrome or primary AL amyloidosis are excluded

Sponsors & Collaborators

• Natalie Callander: lead
• Sanofi: collaborator
• Karyopharm Therapeutics Inc: collaborator
• University of Wisconsin, Madison: collaborator

Study Sites (1)

University of Wisconsin

Madison, Wisconsin, 53705, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

selinexor; carfilzomib; isatuximab; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Natalie Callander, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Natalie Callander, MD

CONTACT

608-265-8690; nsc@medicine.wisc.edu

Ahran Lee

CONTACT

317-634-5842; alee@hoosiercancer.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: March 13, 2026
• First Posted: March 18, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2029
• Last Updated: May 14, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)