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

Primary Purpose

Amyloid, Amyloidosis, AL Amyloidosis

Status

Withdrawn

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Selinexor

Dexamethasone

About this trial

This is an interventional treatment trial for Amyloid

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

Weill Cornell Medicine - Multiple Myeloma Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

selinexor/ dexamethasone (Sd)

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Compare Hematologic Overall Response Rate (ORR)

Comparing proportion of subjects with Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), No Response (NR) and Progressive Disease (PD)

Hematologic Very Good Partial Response (VGPR) or better rate

Percentage of subjects that achieved Very Good Partial Response (VGPR) or better response

Hematologic Complete Response (CR) rate

Percentage of subjects that achieved Complete Response (CR)

Stringent dFLC response rate

Percentage of subjects that has stringent dFLC (dFLC is defined as the difference in involved amyloidogenic and uninvolved serum-free light chains).

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

For each subject, detection of monoclonal protein will be analyzed at screening, day 1 of each cycle (only when in ≥VGPR), at each end of treatment (EOT) visits, and day 1 of each post-treatment follow, up until PD or 24 months, whichever occurs first.

minimal residual disease (MRD) negative CR/VGPR rate

Percentage of subjects that is MRD negative when in complete response (CR) and Very Good Partial Response (VGPR)

Percentage of participants with organ response

Organ response for kidney and cardiac is defined as the proportion of baseline organ involved participants who achieve organ response in each corresponding organ. Organ response defined for cardiac: N-terminal brain pronatriuretic peptide (NT-proBNP) response (> 30% and > 300 nanogram per liter [ng/L] decrease in participants with baseline NT-proBNP >= 650 ng/L) or New York Heart Association (NYHA) class response (>= 2 class decrease in participants with baseline NYHA class 3 or 4); for kidney: decrease in proteinuria by >=30% or below 0.5 grams /24 hours without renal progression.

Median hematologic Progression Free Survival (PFS)

Median estimate of months that participants have progression free survival and median estimate is calculated using the Kaplan-Meier methodology

Time to first hematologic response

Measured in months between the date of enrollment and the first efficacy evaluation at which the participant has met the criteria for hematologic complete response.

Time to best hematologic response

Measured in months between the date of enrollment and the best hematologic response the subject achieved while on treatment

Time to hematologic progression

Measured in months between the date of enrollment and the first efficacy evaluation at which the participant has met the criteria for hematologic progression

Duration of hematologic response

Duration of hematologic response is defined as the time between the date of initial documentation of hematologic response (i.e. Complete Response, Very Good Partial Response, Partial Response, No Response and Progressive Disease) to the date of the next hematologic response

Time to next therapy

Measured in months from the date of enrollment to the start date of subsequent treatment for AL amyloidosis

Median organ Progression Free Survival (PFS)

Measured in months between the date of enrollment and the first efficacy evaluation at which the participant has met the criteria for hematologic complete response.

Time to organ response

Measured in months between the date of enrollment and the organ response

Time to organ progression

Measured in months between the date of organ response to organ progression

Duration of organ response

Measured in months between the date of initial documentation of organ response to organ progression

Full Information

NCT ID

NCT04984330

First Posted

July 29, 2021

Last Updated

November 11, 2022

Sponsor

Weill Medical College of Cornell University

Collaborators

Karyopharm Therapeutics Inc

1. Study Identification

Unique Protocol Identification Number

NCT04984330

Brief Title

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

Acronym

STARR

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Withdrawn

Why Stopped

Funding withdrawn

Study Start Date

December 2021 (Anticipated)

Primary Completion Date

June 2023 (Anticipated)

Study Completion Date

June 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Weill Medical College of Cornell University

Collaborators

Karyopharm Therapeutics Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Amyloid, Amyloidosis, AL Amyloidosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

selinexor/ dexamethasone (Sd)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Selinexor

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Dexamethasone

Intervention Description

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).

Primary Outcome Measure Information:

Title

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

Description

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

Time Frame

approximately 12 months

Secondary Outcome Measure Information:

Title

Compare Hematologic Overall Response Rate (ORR)

Description

Comparing proportion of subjects with Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), No Response (NR) and Progressive Disease (PD)

Time Frame

approximately 12 months

Title

Hematologic Very Good Partial Response (VGPR) or better rate

Description

Percentage of subjects that achieved Very Good Partial Response (VGPR) or better response

Time Frame

approximately 12 months

Title

Hematologic Complete Response (CR) rate

Description

Percentage of subjects that achieved Complete Response (CR)

Time Frame

approximately 12 months

Title

Stringent dFLC response rate

Description

Percentage of subjects that has stringent dFLC (dFLC is defined as the difference in involved amyloidogenic and uninvolved serum-free light chains).

Time Frame

approximately 12 months

Title

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

Description

Time Frame

End of Study (approximately 3 years)

Title

minimal residual disease (MRD) negative CR/VGPR rate

Description

Percentage of subjects that is MRD negative when in complete response (CR) and Very Good Partial Response (VGPR)

Time Frame

approximately 12 months

Title

Percentage of participants with organ response

Description

Time Frame

End of Study (approximately 3 years)

Title

Median hematologic Progression Free Survival (PFS)

Description

Median estimate of months that participants have progression free survival and median estimate is calculated using the Kaplan-Meier methodology

Time Frame

End of Study (approximately 3 years)

Title

Time to first hematologic response

Description

Measured in months between the date of enrollment and the first efficacy evaluation at which the participant has met the criteria for hematologic complete response.

Time Frame

approximately 12 months

Title

Time to best hematologic response

Description

Measured in months between the date of enrollment and the best hematologic response the subject achieved while on treatment

Time Frame

approximately 12 months

Title

Time to hematologic progression

Description

Measured in months between the date of enrollment and the first efficacy evaluation at which the participant has met the criteria for hematologic progression

Time Frame

End of Study (approximately 3 years)

Title

Duration of hematologic response

Description

Time Frame

End of Study (approximately 3 years)

Title

Time to next therapy

Description

Measured in months from the date of enrollment to the start date of subsequent treatment for AL amyloidosis

Time Frame

End of Study (approximately 3 years)

Title

Median organ Progression Free Survival (PFS)

Description

Measured in months between the date of enrollment and the first efficacy evaluation at which the participant has met the criteria for hematologic complete response.

Time Frame

End of Study (approximately 3 years)

Title

Time to organ response

Description

Measured in months between the date of enrollment and the organ response

Time Frame

approximately 12 months

Title

Time to organ progression

Description

Measured in months between the date of organ response to organ progression

Time Frame

End of Study (approximately 3 years)

Title

Duration of organ response

Description

Measured in months between the date of initial documentation of organ response to organ progression

Time Frame

End of Study (approximately 3 years)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Cara Rosenbaum, MD

Organizational Affiliation

Weill Medical College of Cornell University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Weill Cornell Medicine - Multiple Myeloma Center

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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