Selinexor for Treatment of Light Chain Amyloidosis With Relapsed/Refractory Disease

NCT04984330 | Withdrawn Early Phase 1 DMC FDA Drug

• 1 other identifier: 21-01023225
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the safety and efficacy of Selinexor and Dexamethasone and see what effects it has on AL amyloidosis.

Conditions

Amyloid; Amyloidosis; AL Amyloidosis

Outcome Measures

Primary Outcomes (1)

• Compare number of dose limiting toxicity (DLT) occurence to measure safety and toxicity

  Safety and toxicity will be determined by how many occurrence of dose limiting toxicity (DLT) occured during 12 months of treatment for each subject

  approximately 12 months

Secondary Outcomes (17)

• Compare Hematologic Overall Response Rate (ORR)

  approximately 12 months

• Hematologic Very Good Partial Response (VGPR) or better rate

  approximately 12 months

• Hematologic Complete Response (CR) rate

  approximately 12 months

• Stringent dFLC response rate

  approximately 12 months

• Number of patients with peripheral blood mass spectrometry for monoclonal protein detection (MALDI-TOF)

  End of Study (approximately 3 years)

Study Arms (1)

selinexor/ dexamethasone (Sd)

EXPERIMENTAL

Selinexor • 60mg PO once weekly on days 1, 8, 15, 22 until disease progression or toxicity Dexamethasone • 20 mg PO administered 30-60 minutes prior to selinexor on days 1, 2, 8, 9, 15, 16, 22, 23

Drug: Selinexor; Drug: Dexamethasone

Interventions

Selinexor DRUG

Selinexor will be given orally at a dose of 60mg once weekly on the first day of the week (day 1, 8, 15, and 22) for Cycle 1 and up to Cycle 12.

selinexor/ dexamethasone (Sd)

Dexamethasone DRUG

Dexamethasone will be given orally at a dose of 20mg, if tolerated, or at a reduced dose if required, 30 to 60 minutes prior to selinexor for first 2 days of each week only (days 1, 2, 8, 9, 15, 16, 22, and 23 of each cycle).

selinexor/ dexamethasone (Sd)

Eligibility Criteria

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

You may qualify if:

• Diagnosis of primary AL amyloidosis
• Relapsed and/or refractory AL amyloidosis
• Measurable disease
• Male or female patients 18 years or older
• Able to give voluntary written consent
• Eastern Cooperative Oncology Group performance status and/or other performance status 0, 1, or 2.
• Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet count ≥ 75,000/mm3.
• Total bilirubin ≤ 1.5 × the upper limit of the normal range (ULN).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN.
• Calculated creatinine clearance ≥ 30 mL/min

You may not qualify if:

• Non-AL amyloidosis
• Clinically overt myeloma
• Prior exposure to Selinexor
• Clinically significant cardiac disease
• Severe obstructive airway disease
• Female patients who are lactating or have a positive serum pregnancy test during the screening period
• Planned high-dose chemotherapy and autologous stem cell transplantation within 6, 28-day treatment cycles after starting on treatment
• Failure to have fully recovered (ie, ≤ Grade 1 toxicity) from the reversible effects of prior chemotherapy.
• Major surgery within 14 days before enrollment.
• Radiotherapy within 14 days before enrollment.
• Infection requiring systemic intravenous antibiotic therapy or other serious infection within 14 days before study enrollment. Systemic treatment, within 14 days before the first dose, with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital, see Appendix 11.7), or use of Ginkgo biloba or St. John's wort.
• Positive for human immunodeficiency virus (HIV), hepatitis B, and hepatitis C
• Serious medical or psychiatric illness
• GI disease or GI procedure that could interfere with the oral absorption or tolerance including difficulty swallowing
• Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Karyopharm Therapeutics Inc: collaborator

Study Sites (1)

Weill Cornell Medicine - Multiple Myeloma Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Alzheimer Disease; Amyloidosis; Immunoglobulin Light-chain Amyloidosis

Interventions

selinexor; Dexamethasone

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias

Intervention Hierarchy (Ancestors)

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

Study Officials

• Cara Rosenbaum, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2021
• First Posted: July 30, 2021
• Study Start: December 1, 2021
• Primary Completion: June 1, 2023
• Study Completion: June 1, 2024
• Last Updated: November 17, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)