Selinexor Treatment for Multiple Myeloma Patients Who Are Refractory to Lenalidomide-containing Therapy.
A Pilot Study Examining Selinexor's Ability to Overcome Resistance in Multiple Myeloma Patients Who Are Refractory to Lenalidomide-containing Therapy.
1 other identifier
interventional
22
1 country
1
Brief Summary
This is a pilot study evaluating the safety and efficacy of selinexor among multiple myeloma (MM) patients that are refractory to lenalidomide-containing regimens with or without steroids.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Nov 2020
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 12, 2020
CompletedFirst Posted
Study publicly available on registry
August 19, 2020
CompletedStudy Start
First participant enrolled
November 1, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 29, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
December 29, 2023
CompletedOctober 31, 2023
October 1, 2023
3.2 years
August 12, 2020
October 30, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Overall Response
Overall Response Rate (\[ORR\]=CR +VGPR+ PR)
30 months
Clinical Benefit Rate
Clinical Benefit Rate (\[CBR\]= CR+VGPR+PR+MR)
30 months
Secondary Outcomes (6)
Adverse Events Occurrences
30 months
Time to progression (TTP)
30 months
Progression-free survival (PFS)
30 months
Time to first response
30 months
Duration of Response (DOR)
30 months
- +1 more secondary outcomes
Other Outcomes (1)
Measuring levels of multiple myeloma specific biomarkers such as M-Protein and BCMA
30 months; duration of each cycle in this study is 28 days
Study Arms (1)
Selinexor/Lenalidomide/Steroids
EXPERIMENTALAll subjects enrolled will receive: 1) selinexor, PO, at 60 mg once weekly on days 1-28 of a 28-day cycle, 2) lenalidomide, PO, 10 mg daily on days 1-21 of 28-days cycle and 3) methylprednisolone at the same dose and schedule as the last lenalidomide-containing regimen if it contained steroids. If patient's qualifying lenalidomide-containing regimen contained different type of steroid (e.g. prednisone, dexamethasone, etc.) then patient on this study will receive methylprednisolone at the equivalent dose and schedule.
Interventions
Selinexor (KPT-330) is a first-in-class, oral selective exportin 1 (XPO1) inhibitor (1,2). Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus along with inhibition of translation of oncoprotein mRNAs.
Eligibility Criteria
You may qualify if:
- Age ≥ 18 year of age.
- Willing and able to provide written informed consent in accordance with federal, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure.
- Able to adhere to the study visit schedule and other protocol requirements.
- ECOG Performance Status (PS) of ≤ 2.
- Has a diagnosis of MM based on standard criteria (9) as follows:
- Major criteria:
- Plasmacytomas on tissue biopsy.
- Bone marrow plasmacytosis (greater than 30% plasma cells).
- Monoclonal immunoglobulin spike on serum electrophoresis IgG greater than 3.5 g/dL or IgA greater than 2.0 g/dL or kappa or lambda light chain excretion greater than 1 g/day on 24-hour urine protein electrophoresis.
- Minor criteria:
- Bone marrow plasmacytosis (10% to 30% plasma cells).
- Monoclonal immunoglobulin present but of lesser magnitude than given under major criteria.
- Lytic bone lesions.
- Normal IgM less than 50 mg/dL, IgA less than 100 mg/dL, or IgG less than 600 mg/dL.
- Any of the following sets of criteria will confirm the diagnosis of multiple myeloma:
- +21 more criteria
You may not qualify if:
- Has received selinexor or another XPO1 inhibitor previously.
- Prior malignancy that required treatment or has shown evidence of recurrence (except for non-melanoma skin cancer or adequately treated cervical carcinoma in situ) during the 5 years prior to randomization. Cancer treated with curative intent for \>5 years previously and without evidence of recurrence will be allowed.
- Has any concurrent medical condition or disease (e.g., uncontrolled active hypertension, uncontrolled active diabetes, active systemic infection, POEMS syndrome \[polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes\], primary amyloidosis, 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.
- Known hypersensitivity to compounds of similar chemical or biological composition to thalidomide and lenalidomide or steroids.
- Concurrent use of other anti-cancer agents or treatments.
- The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
- Severe hypercalcemia, i.e., serum calcium ≥ 12 mg/dL (3.0 mmol/L) corrected for albumin
- Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
- Pregnant or breastfeeding females.
- BSA \<1.4 m2 at baseline, calculated by the Dubois (58) or Mosteller (59) method.
- Life expectancy of less than 3 months.
- Major surgery within 4 weeks prior to C1D1.
- Active, unstable cardiovascular function, as indicated by the presence of:
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Oncotherapeuticslead
- Karyopharm Therapeutics Inccollaborator
Study Sites (1)
James R Berenson, MD, Inc.
West Hollywood, California, 90069, United States
Related Publications (2)
Abdul Razak AR, Mau-Soerensen M, Gabrail NY, Gerecitano JF, Shields AF, Unger TJ, Saint-Martin JR, Carlson R, Landesman Y, McCauley D, Rashal T, Lassen U, Kim R, Stayner LA, Mirza MR, Kauffman M, Shacham S, Mahipal A. First-in-Class, First-in-Human Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Patients With Advanced Solid Tumors. J Clin Oncol. 2016 Dec;34(34):4142-4150. doi: 10.1200/JCO.2015.65.3949. Epub 2016 Oct 31.
PMID: 26926685BACKGROUNDGounder MM, Zer A, Tap WD, Salah S, Dickson MA, Gupta AA, Keohan ML, Loong HH, D'Angelo SP, Baker S, Condy M, Nyquist-Schultz K, Tanner L, Erinjeri JP, Jasmine FH, Friedlander S, Carlson R, Unger TJ, Saint-Martin JR, Rashal T, Ellis J, Kauffman M, Shacham S, Schwartz GK, Abdul Razak AR. Phase IB Study of Selinexor, a First-in-Class Inhibitor of Nuclear Export, in Patients With Advanced Refractory Bone or Soft Tissue Sarcoma. J Clin Oncol. 2016 Sep 10;34(26):3166-74. doi: 10.1200/JCO.2016.67.6346. Epub 2016 Jul 25.
PMID: 27458288BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
James R Berenson, MD
Oncotherapeutics
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 12, 2020
First Posted
August 19, 2020
Study Start
November 1, 2020
Primary Completion
December 29, 2023
Study Completion
December 29, 2023
Last Updated
October 31, 2023
Record last verified: 2023-10
Data Sharing
- IPD Sharing
- Will not share
We will share overall demographics of the study population, clinical responses, AEs and SAEs.