Selinexor for the Treatment of Intermediate and High-Risk Smoldering Multiple Myeloma

NCT05597345 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: UMMMY22027
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Selinexor is a drug that has been approved in the treatment of patients with symptomatic multiple myeloma. The standard of care for patients with Smoldering Multiple Myeloma remains observation, but there are numerous clinical trials investigating interventions to delay progression to multiple myeloma and prevent or delay disease related outcomes. A subset of patients with intermediate or high risk smoldering multiple myeloma have a much higher risk of progressive to multiple myeloma, while the low risk smoldering myeloma patient population has a much lower risk. This is a clinical trial investigating the use of low-dose selinexor in patients with intermediate to high-risk smoldering multiple myeloma. The investigators hypothesize that the use of selinexor in intermediate to high risk smoldering myeloma patients will help to delay progression of disease to symptomatic multiple myeloma.

Conditions

Smoldering Multiple Myeloma

Keywords

Smoldering Multiple Myeloma; Smoldering Myeloma; Multiple Myeloma; Myeloma; MGUS

Outcome Measures

Primary Outcomes (1)

• Rate of progression to Multiple Myeloma

  The study will assess how long participants will not have the cancer get worse while treated with selinexor

  2 years after end of treament

Secondary Outcomes (4)

• Change in monoclonal protein (M-spike) or serum free light chains (sFLC)

  1 Year

• Progression free survival

  1 Year

• Rate of skeletal related events

  1 Year

• rate of adverse events

  1 year

Study Arms (1)

Experimental: Treatment

EXPERIMENTAL

Selinexor 40mg weekly for up to 12 cycles. Each cycle will be 28 days in length.

Drug: Selinexor

Interventions

Selinexor DRUG

Low-dose Selinexor for the Treatment of Intermediate to High-Risk Smoldering Multiple Myeloma

Experimental: Treatment

Eligibility Criteria

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

You may qualify if:

• Age \>/= 18 years
• Histologically confirmed diagnosis of SMM according to the IMWG definition: serum M-protein \>/= 3 g/dL or BMPC \>10% but \<60%, or both.
• Should not meet CRAB criteria: hypercalcemia, anemia, bone lesions, or renal insufficiency thought to be related to the plasma cell disorder.
• Should have 1 of the following risk factors to be considered intermediate risk and 2 or more risk factors to be considered high-risk:
• BMPC\>/=20%
• M-spike \>/= 2g/dL
• Involved to uninvolved sFLC ratio of \>/= 20
• normal hepatic function within 28 days prior to C1D1
• Adequate renal function within 28 days prior to C1D1. Estimated creatinine clearance (CrCl) calculated using formula of Cockcroft and Gault. CrCl \>/= 15 mL/min.
• Adequate hematopoietic function within 28 days prior to C1D1: absolute neutrophil count (ANC)\>/=1.5 x10\^9/L, hemoglobin \>/=10g/dL, platelets \>/150x10\^9/L.
• Life expectancy of \>12 months.
• ECOG PS 0-1
• Subjects with reproductive potential must use 2 highly effective methods of effective contraception or practice sexual abstinence throughout the study and continue for 6 months after the study has closed. Subjects who are surgically sterile (e.g., history of bilateral tubal ligation, hysterectomy, or whos partner is sterile are not required to use additional modes of contraception.
• Ability to understand and willingness

You may not qualify if:

• Meets criteria for symptomatic MM as defined by any of the following, determined to be related to the plasma cell disorder
• Hypercalcemia (corrected serum calcium \>11.0 mg/dL)
• Renal insufficiency (creatinine \>2.0 mg/dL)
• Anemia (hemoglobin \<10g/dL)
• One or more osteolytic bone lesions on radiography, but more than one lesion required if \<10% clonal bone marrow plasma cells. Based on MRI imaging, there must be more than one lesion \>5mm in size.
• Clonal bone marrow plasma cells ≥60%
• An involved serum free light chain ≥ 100mg/L with the ratio of the involved/uninvolved free light chains also ≥100
• Documented systemic light chain amyloidosis
• Systemic corticosteroids \>10mg prednisone (or equivalent) daily for other medical conditions.
• Active invasive malignancy within the past 3 years that may affect the results or interfere with the interpretation of results of this study.
• Non-invasive malignancy that was not treated with curative intent within the past 3 years that may affect the results or interfere with the interpretation of the results of this study.
• Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 14 days of the receiving the first dose
• Known active HIV infection without adequate anti-retroviral therapy
• Active gastrointestinal dysfunction that prevents patient from swallowing tablets or may interfere with absorption of study treatment
• Pregnant, breast feeding, or planning to become pregnant within 6 months after the end of treatment.

Sponsors & Collaborators

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

Study Sites (1)

University of Rochester

Rochester, New York, 14642, United States

RECRUITING

MeSH Terms

Conditions

Smoldering Multiple Myeloma; Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

selinexor

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Hypergammaglobulinemia; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Paraproteinemias; Immunoproliferative Disorders; Immune System Diseases; Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders

Study Officials

• Jodi Lipof

  University of Rochester

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jodi Lipof

CONTACT

6505042400; jodi_lipof@urmc.rochester.edu

Brea Lipe

CONTACT

Brea_Lipe@urmc.rochester.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 - Department of Medicine , Hematology/Oncology (SMD)

Model Details: This is a single-center, open-label, phase 2, single-arm clinical trial of selinexor in patients with intermediate to high-risk smoldering multiple myeloma. Intermediate-risk patients will start enrolling after 5 high-risk smoldering myeloma patients have been enrolled and received 1-2 cycles of treatment. Patients will receive selinexor 40mg orally weekly for up to 12 cycles. Each cycle will be 28 days in length. Patients will receive treatment up to 1 year and continue in follow-up for 2 years after completion of the treatment period.

Study Record Dates

• First Submitted: October 24, 2022
• First Posted: October 28, 2022
• Study Start: August 21, 2023
• Primary Completion: October 29, 2024
• Study Completion: December 31, 2025
• Last Updated: February 10, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)