Clinical trial NCT04984330: Selinexor for Treatment of Light Chain Amyloidosis With Relapsed/Refractory Disease
Official title: Selinexor for Treatment of Light Chain Amyloidosis With Relapsed/Refractory Disease
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Amyloid
Amyloidosis
AL Amyloidosis
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: Karyopharm Therapeutics Inc
First posted: 2021-07-30
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.
* Participation in another clinical trials involving investigational agents within 30 days of starting this trial
* Peripheral neuropathy (grade 2 with pain or grade 3 or higher).

Primary outcomes:
measure: Compare number of dose limiting toxicity (DLT) occurence to measure safety and toxicity
timeFrame: approximately 12 months
Secondary outcomes:
measure: Compare Hematologic Overall Response Rate (ORR)
timeFrame: approximately 12 months
measure: Hematologic Very Good Partial Response (VGPR) or better rate
timeFrame: approximately 12 months
measure: Hematologic Complete Response (CR) rate
timeFrame: approximately 12 months
measure: Stringent dFLC response rate
timeFrame: approximately 12 months
measure: Number of patients with peripheral blood mass spectrometry for monoclonal protein detection (MALDI-TOF)
timeFrame: End of Study (approximately 3 years)
measure: minimal residual disease (MRD) negative CR/VGPR rate
timeFrame: approximately 12 months
measure: Percentage of participants with organ response
timeFrame: End of Study (approximately 3 years)
measure: Median hematologic Progression Free Survival (PFS)
timeFrame: End of Study (approximately 3 years)
measure: Time to first hematologic response
timeFrame: approximately 12 months
measure: Time to best hematologic response
timeFrame: approximately 12 months
measure: Time to hematologic progression
timeFrame: End of Study (approximately 3 years)
measure: Duration of hematologic response
timeFrame: End of Study (approximately 3 years)
measure: Time to next therapy
timeFrame: End of Study (approximately 3 years)
measure: Median organ Progression Free Survival (PFS)
timeFrame: End of Study (approximately 3 years)
measure: Time to organ response
timeFrame: approximately 12 months
measure: Time to organ progression
timeFrame: End of Study (approximately 3 years)
measure: Duration of organ response
timeFrame: End of Study (approximately 3 years)
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medicine - Multiple Myeloma Center
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Cara Rosenbaum, MD
role: PRINCIPAL_INVESTIGATOR
References: