Selinexor Maintenance Post CAR-T Cell Therapy for Multiple Myeloma

The outcomes in patients with relapsed multiple myeloma refractory to triple-therapy (anti-CD38, immunomodulatory drugs (IMiD) and proteasome inhibitors (PI)) remain poor. These patients are eligible for chimeric antigen receptor T-cells (CAR-T), which rely on redirecting autologous T-cells to clear myeloma cells by targeting B-cell maturation antigen (BCMA). BCMA CAR-T therapy is not curative, and unlike autologous stem cell transplant, there is currently no standard for maintenance therapy post CAR-T which could potentially increase MRD rates and extend progression-free survival.

Selinexor is an exportin (XPO1) inhibitor with direct anti-tumor effect used often as an adjunct with other agents as bridging therapy prior to CAR-T. As selinexor does not affect T-cell yields or fitness, T-cell collection on selinexor for CAR-T manufacturing is safe.

The aim of this study is to evaluate the safety and toxicity of selinexor in triple-exposed or refractory multiple myeloma patients with high-risk features (adverse risk cytogenetics, less than complete response (CR) post CAR-T, or extramedullary disease) following BCMA CAR-T therapy. The investigators hypothesize that selinexor as maintenance therapy following CAR-T has the potential to act synergistically with CAR-T cells leading to more durable responses.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Selinexor

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Mark A Schroeder, M.D.; Phone Number: 314-454-8306; Email: markschroeder@wustl.edu

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Sub-Investigator: Feng Gao, Ph.D.
      • Sub-Investigator: Keith Stockerl-Goldstein, M.D.
      • Sub-Investigator: Ravi Vij, M.D.
      • Sub-Investigator: Michael Slade, M.D.
      • Contact: Mark A Schroeder, M.D.; Phone Number: 314-454-8306; Email: markschroeder@wustl.edu
      • Principal Investigator: Mark A Schroeder, M.D.
      • Sub-Investigator: Arun Cumpelik, M.D., Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of triple-class exposed or refractory multiple myeloma (MM). Diagnosis must be histologically confirmed. Patients with multiple myeloma with local amyloid deposition in the bone marrow are eligible. Only the following risk categories will be enrolled:

  • High risk myeloma, defined by the presence of at least one of the following features:

    • Deletion 17p and/or TP53 alteration:

      • Deletion of 17p with a cancer clonal fraction (CCF) ≥20%, assessed on CD138-positive/purified plasma cells, AND/OR
      • TP53 mutation identified using a validated next-generation sequencing (NGS)-based assay.

    • High-risk IgH translocation with chromosome 1 abnormality:

      • Presence of t(4;14), t(14;16), or t(14;20) in combination with either gain/amplification of 1q (1q+) and/or deletion of 1p32.

    • Chromosome 1p32 deletion patterns:

      • Monoallelic deletion of 1p32 occurring with gain/amplification of 1q, OR
      • Biallelic deletion of 1p32.

    • Elevated β2-microglobulin without renal dysfunction:

      • Serum β2-microglobulin ≥5.5 mg/L in the setting of normal renal function, defined as serum creatinine <1.2 mg/dL.
    • Presence of extramedullary disease prior to receiving CAR-T OR
  • Standard risk myeloma with MRD-positive (MRD+) disease at MRD draw around Day 58-60 post CAR-T.
• Received standard of care ciltacabtagene autoleucel (cilta-cel; Carvykti).
• Able to monitor disease response by ClonoSEQ MRD testing.
• At least 18 years of age.
• ECOG performance status ≤ 2.

• Adequate bone marrow and organ function as defined below:

  • Absolute neutrophil count ≥ 1.0 K/cumm
  • Platelets ≥ 50 K/cumm
  • Hemoglobin ≥ 8.5 g/dL without blood transfusion within 7 days before C1D1.
  • Total bilirubin ≤ 1.5 x IULN; patients with Gilbert's syndrome must have a total bilirubin < 3 x IULN.
  • AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN
  • Calculated creatinine clearance ≥ 15 mL/min by Cockcroft-Gault
• The effects of selinexor on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to C1D1 of selinexor, for the duration of study participation, and for 90 days after completion of selinexor. Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, s/he must inform her treating physician immediately.
• Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

Exclusion Criteria:

• MM with active CNS involvement.
• Confirmed progressive disease by IMWG after CAR-T administration.
• Unresolved cytokine release syndrome (CRS) or CAR-T neurologic toxicity.
• Any unresolved non-hematologic grade ≥ 3 treatment-related toxicity from CAR-T.
• Administration or planned administration of any other concomitant chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy which would be considered a treatment of multiple myeloma from Day 28 post-CAR-T cell therapy through discontinuation from study treatment. Note: patients may be on corticosteroids if they are being given for disorders other than multiple myeloma (e.g., adrenal insufficiency, rheumatoid arthritis)
• Has received selinexor or another XPO1 inhibitor post-CART.
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
• Prior organ transplant requiring immunosuppressive therapy.
• Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial
• Currently receiving any other investigational agents.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to selinexor or other agents used in the study.
• Active gastrointestinal dysfunction interfering with the patient's ability to swallow tablets, or any active gastrointestinal dysfunction that could interfere with absorption of study treatment.
• Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to C1D1 of selinexor (patients on prophylactic antibiotics or with a controlled infection within 1 week prior to C1D1 of selinexor may enroll); active, unstable cardiovascular function, as indicated by the presence of symptomatic ischemia, uncontrolled clinically significant conduction abnormalities (e.g. patients with ventricular or atrial tachycardia on anti-arrhythmics are excluded; patients with first degree atrioventricular block or asymptomatic left anterior fascicular block/right bundle branch block will not be excluded), congestive heart failure of NYHA class ≥ 3 or known left ventricular ejection fraction of < 40%, or myocardial infraction within 3 months prior to C1D1 of selinexor therapy.
• Major surgery within 28 days prior to C1D1 of selinexor
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of C1D1 of selinexor.
• HIV-infected if not on effective anti-retroviral therapy with undetectable viral load for 6 months. Patients with HIV who are receiving effective anti-retroviral therapy and have had an undetectable viral load for at least 6 months are eligible. HIV testing not required in the absence of known history of infection.
• Evidence of chronic hepatitis B virus (HBV) that is detectable on suppressive therapy. Patients with evidence of chronic HBV infection with undetectable HBV viral load on suppressive therapy are eligible. HBV testing not required in the absence of known history of infection.
• History of hepatitis C virus (HCV) infection that has not been cured or that has a detectable viral load. Patients with a history of HCV that has been treated and cured are eligible. Patients with HCV infection who are currently on treatment and have an undetectable HCV viral load are eligible. HCV testing not required in the absence of known history of infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Selinexor; Patients with high risk of relapse will receive maintenance selinexor starting at Day 30 (high risk MM patients) or after Day 58 (for MRD+ patients) post-cilta-cel infusion and will continue selinexor for up to 12 cycles. Selinexor will be given weekly on Days 1, 8, 15, and 22 of each 28-day cycle. The first 3 to 6 patients enrolled will be part of the safety run-in cohort; these patients will be monitored for dose-limiting toxicities during Cycle 1.

Drug: Selinexor; Selinexor will be provided by Karyopharm Therapeutics, Inc.; Other Names: KPT-330; Xpovio

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Tolerability as measured by rate of patients who received > 80% of cumulative selinexor dose during the study period	Through completion of selinexor treatment (estimated to be 12 months)
Rate of non-hematologic grade ≥ 3 treatment-related adverse events (excluding conditioning and CAR-T related adverse events) according to CTCAE v 6.0	From start of selinexor through 30 days after the last dose of selinexor (estimated to be 13 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of MRD negativity by clonoSEQ sensitive to 10-5		At 6 months after CAR-T infusion
Rate of MRD negativity by clonoSEQ sensitive to 10-5		At 12 months after CAR-T infusion
Progression-free survival (PFS)	PFS is defined as: The time from initiation of treatment to the occurrence of either objective disease progression (by IMWG criteria) or death from any cause, whichever comes first.	At 6 months after CAR-T infusion
Progression-free survival (PFS)	PFS is defined as: The time from initiation of treatment to the occurrence of either objective disease progression (by IMWG criteria) or death from any cause, whichever comes first.	At 12 months after CAR-T infusion
Time to progression (TTP)	TTP is defined as: The interval from initiation of therapy to the first documentation of disease progression, as determined by IMWG criteria.	Through completion of follow-up (estimated to be 24 months)
Duration of response (DOR)	DOR is defined as: The time interval from the first documented evidence of a partial response or better after starting treatment by IMWG criteria to the occurrence of disease progression (by IMWG criteria) or death from any cause.	Through completion of follow-up (estimated to be 24 months)
Rate of complete response (CR) and stringent CR (sCR) by IMWG response criteria	sCR: Stringent complete response requires all of the following:CR as defined belowNormal free light chain ratio (0.26-1.65)Absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence; CR: Complete response requires all of the following:Negative immunofixation on the serum and urineNormal free light chain ratio (0.26-1.65)<5% plasma cells in the bone marrow aspirateDisappearance of any soft tissue plasmacytomas	At 6 months after CAR-T infusion
Rate of complete response (CR) and stringent CR (sCR) by IMWG response criteria	sCR: Stringent complete response requires all of the following:CR as defined belowNormal free light chain ratio (0.26-1.65)Absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence; CR: Complete response requires all of the following:Negative immunofixation on the serum and urineNormal free light chain ratio (0.26-1.65)<5% plasma cells in the bone marrow aspirateDisappearance of any soft tissue plasmacytomas	At 12 months after CAR-T infusion

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Karyopharm Therapeutics Inc
• Investigators: Principal Investigator: Mark A Schroeder, M.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2026
• Primary Completion (Estimated): April 30, 2029
• Study Completion (Estimated): March 31, 2031

Study Registration Dates

• First Submitted: September 22, 2025
• First Submitted That Met QC Criteria: September 22, 2025
• First Posted (Actual): September 30, 2025

Study Record Updates

• Last Update Posted (Actual): June 8, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Multiple Myeloma; Maintenance; Selinexor; Cilta-cel
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; selinexor
• Other Study ID Numbers: 202511028 (Nanjing Municipal Science and Technology Bureau)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported after deidentification
• IPD Sharing Time Frame: Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata.

IPD Sharing Access Criteria

Investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose. Analysis will be performed to achieve the aims of the approved proposal.

Contact the PI regarding proposal submission and accessing data.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No