Selinexor, Venetoclax, and Dexamethasone (XVenD) in t(11;14)-Positive Relapsed/Refractory Multiple Myeloma

NCT05530421 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 20220595
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this research is to determine whether the combination of selinexor, venetoclax, and dexamethasone therapy can increase anti-cancer effects in patients with translocation 11;14-positive (t(11;14)), relapsed/refractory myeloma (RRMM).

Conditions

Relapsed and Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Fraction of Participants Achieving Overall Response

  Overall response rate (ORR) will be reported as the fraction of participants achieving either complete response (CR) or partial response (ORR = CR + PR) to study treatment. Response to therapy will be assessed by treating physician using International Myeloma Working Group 2016 response criteria.

  Up to 3 years

Secondary Outcomes (5)

• Duration of Response (DoR)

  Up to 3 years

• Minimal Residual Disease Negative Complete Response Rate

  Up to 3 years

• Progression-Free Survival (PFS)

  Up to 3 years

• Overall Survival (OS)

  Up to 3 years

• Rate of Treatment-Emergent Adverse Events

  Up to 10 months

Study Arms (1)

XVenD Group

EXPERIMENTAL

Participants will receive XVenD combination therapy of Selinexor (X), Venetoclax (Ven) and Dexamethasone (D) orally during each 28-day cycle. Doses will be administered as follows: * Cycle 1 Days 1 to 7: * Venetoclax 400 mg orally (PO), Days 1-7 * Dexamethasone 40 mg PO, Day 1 * Cycle 1 Days 8 to 28: * Venetoclax 800 mg PO, Days 8-28 * Dexamethasone 40 mg PO, Days 8, 15, and 22 * Cycles 2 to 4: * Selinexor 80 mg PO, Days 1, 8, 15, and 22 * Venetoclax 800 mg PO, Days 1-28 * Dexamethasone 40 mg PO, Days 1, 8, 15, and 22 * Cycle 5 and beyond: * Selinexor 80 mg PO, Days 1, 8, 15, and 22 * Venetoclax 800 mg PO, Days 1-28 * Dexamethasone 20 mg PO, Days 1, 8, 15, and 22 Selinexor dose will be reduced to 60 mg for remaining participants if after the first 6 participants complete the first cycle and 2 or more out of these first 6 participants experience dose-limiting toxicities (DLTs).

Drug: Selinexor; Drug: Venetoclax; Drug: Dexamethasone

Interventions

Selinexor DRUG

Selinexor tablets will be administered orally (PO) once per day at assigned dosage and frequency per protocol.

Also known as: Xpovio

XVenD Group

Venetoclax DRUG

Venetoclax tablets will be administered orally (PO) once per day at assigned dosage and frequency per protocol.

Also known as: Venclexta, Venclyxto

XVenD Group

Dexamethasone DRUG

Dexamethasone tablets will be administered orally (PO) once per day at assigned dosage and frequency per protocol.

Also known as: Decadron, Ozurdex, Dexycu

XVenD Group

Eligibility Criteria

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

You may qualify if:

• Patients must have a documented diagnosis of multiple myeloma defined by the International Myeloma Working Group Criteria (IMWG).5 Patients at initial diagnosis must have had a serum M-protein ≥ 3 g/dL and/or bone marrow plasma cells ≥10%, and at least one of the following:
• Anemia: Hemoglobin ≤10 g/dL, or
• Renal failure: serum creatinine ≥ 2.0 mg/dL, or
• Hypercalcemia: Ca ≥10.5 mg/dL, or
• Lytic bone lesions on X-ray, CT, or Positron emission tomography/Computed Tomography (PET/CT), or
• ≥ 2 focal lesions on spinal magnetic resonance imaging (MRI), or
• ≥ 60% bone marrow plasma cells, or Involved/un-involved serum free light chain ratio ≥ 100. Age ≥18 years of age on day of signing informed consent.
• Patients must have had a bone marrow (BM) biopsy proven plasma cell myeloma harboring the t(11;14) translocation as reported by a Clinical Laboratory Improvement Amendments (CLIA) certified assay (i.e. local fluorescence in situ hybridization (FISH) testing). BM biopsy can be performed at time of enrollment or documented FISH results (i.e. original FISH report) can be used.
• Must have Relapsed or Relapsed and Refractory Multiple Myeloma. Patients must have documented evidence of having received two prior lines of therapy and be refractory to, not a candidate for (ineligible), or intolerant of at least one immunomodulatory (IMiD), one proteasome inhibitor, and one anti-cluster of differentiation 38 (anti-CD38) monoclonal antibody-based treatments.
• Documented measurable disease based on the IMWG guidelines within the 4 weeks prior to registration defined by any one of the following criteria:
• Serum monoclonal protein ≥ 0.5 g/dl
• Urine monoclonal protein \>200 mg/24 hour
• Serum immunoglobulin free light chain \>10 mg/dL AND abnormal kappa/lambda ratio
• Bone marrow plasma cells ≥ 30%
• A measurable lesion on PET/CT or MRI ≥ 2 cm

You may not qualify if:

• Has received selinexor or another specific inhibitor of nuclear exporter (SINE) compound previously.
• Has any concurrent medical condition or disease (eg, uncontrolled active hypertension, uncontrolled active diabetes, active systemic infection, etc.) that is likely to interfere with study procedures.
• Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to Cycle 1 Day 1 (C1D1). Patients on prophylactic antibiotics or with a controlled infection within 1 week prior to C1D1 are acceptable.
• Known intolerance, hypersensitivity, or contraindication to glucocorticoids.
• Pregnant or breastfeeding females.
• Active, unstable cardiovascular function, as indicated by the presence of symptomatic ischemia, or Uncontrolled clinically significant conduction abnormalities (eg, patients with ventricular 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), or Congestive heart failure of New York Heart Association Class ≥3 or known left ventricular ejection fraction \<40%, or Myocardial infarction within 3 months prior to C1D1.
• Subjects with active hepatitis B virus (Hep B) are allowed if antiviral therapy for hepatitis B has been given for \>8 weeks and viral load is \<100 IU/ml prior to first dose of trial treatment. Subjects with untreated hepatitis C virus (HCV) are allowed. Subjects with Human Immunodeficiency Virus (HIV) who have cluster of differentiation 4-positive (CD4+) T-cell counts ≥ 350 cells/µL and no history of AIDS-defining opportunistic infections in the last year are allowed.
• Any 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.
• Inability or unwillingness to take supportive medications such as anti-nausea and anti-anorexia agents as recommended by the National Comprehensive Cancer Network® (NCCN) Clinical Practice Guidelines in Oncology (CPGO) (https://www.nccn.org/guidelines/category\_3) for antiemesis and anorexia/cachexia (palliative care).
• Any active, serious psychiatric, medical, or other conditions/situations that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give informed consent.
• Contraindication to any of the required concomitant drugs or supportive treatments.
• Patients unwilling or unable to comply with the protocol or known mental or physical illness that would interfere with cooperation with the requirements of the trial or confound the results or interpretation of the results of the trial and, in the opinion of the treating investigator, would make the patient inappropriate for entry into the study.

Sponsors & Collaborators

• University of Miami: lead
• Karyopharm Therapeutics Inc: collaborator

Study Sites (3)

University of Miami, Lennar Foundation Medical Center

Coral Gables, Florida, 33146, United States

RECRUITING

University of Miami, Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, 33442, United States

RECRUITING

University of Miami, Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

RECRUITING

MeSH Terms

Conditions

Recurrence; Multiple Myeloma

Interventions

selinexor; venetoclax; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; 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; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Dickran Kazandjian, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alanna Vossen

CONTACT

305-243-7701; avossen@miami.edu

Dickran Kazandjian, MD

CONTACT

dkazandjian@miami.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: September 2, 2022
• First Posted: September 7, 2022
• Study Start: March 26, 2023
• Primary Completion (Estimated): March 26, 2028
• Study Completion (Estimated): March 26, 2030
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)