High-risk primary refractory MDS patients MedDRA version: 21.1 Level: PT Classification code 10028533 Term: Myelodysplastic syndrome System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10028535 Term: Myelodysplastic syndrome unclassifiable System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: LLT Classification code 10028534
Conditions
Interventions
Product Name: Eltanexor (KPT-8602)
Product Code: Eltanexor (KPT-8602)
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ELTANEXOR
CAS Number: 1642300-52-4
Current Sponsor code: KPT-8602
Con
Sponsors
Karyopharm Therapeutics Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent obtained prior to any screening procedures and in accordance with federal, local, and institutional guidelines. 2. Age =18 years. 3. Adequate hepatic function: a. total bilirubin =2 times the upper limit of normal (ULN) (except patients with Gilbert’s syndrome [hereditary indirect hyperbilirubinemia] who must have a total bilirubin of =4 times ULN), b. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 times ULN (except patients with known liver involvement of their tumor who must have their AST and ALT =5.0 times ULN). 4. Adequate renal function: estimated creatinine clearance of =30 mL/min, calculated using the formula of Cockcroft and Gault (140-Age) × Mass (kg)/(72 × creatinine mg/dL); multiply by 0.85 if female. 5. Female patients of child-bearing potential must agree to use dual methods of contraception (including 1 highly effective and 1 effective method of contraception) and have a negative serum test at Screening, and male patients must use an effective barrier method of contraception if sexually active. For both male and female patients, effective methods of contraception must be used throughout the study and for 3 months following the last dose. 6. Documented diagnosis of MDS with 5% to 19% myeloblasts in the bone marrow (2016 WHO classification). 7. The marrow histopathology must be documented by recent bone marrow biopsy. 8. Patients should be intermediate-, high- or very-high-risk MDS by IPSS-R. 9. Patients with HMA (primary)-refractory MDS, including: a. =2 cycles of hypomethylating agents (azacitidine and/or decitabine, ASTX727, or experimental agents) with clear progressive disease (PD) (pancytopenia , with =50% increase in bone marrow blasts) or patient progresses to a higher-risk category of MDS OR b. =4 cycles of azacitidine and/or decitabine (or other hypomethylating therapy) with SD/lack of improvement (no CR/mCR/PR/HI) per IWG criteria. 10. Eastern Cooperative Oncology Group (ECOG) performance status of =65 years) yes F.1.3.1 Number of subjects for this age range 62
Exclusion criteria
Exclusion criteria: 1. Female patients who are pregnant or lactating. 2. Major surgery within four weeks before C1D1. 3. Impaired cardiac function or clinically significant cardiac diseases, including any of the following: a. Unstable angina or acute myocardial infarction =3 months prior to C1D1; b. Clinically significant heart disease (e.g., symptomatic congestive heart failure [e.g., >NYHA Class 2]; uncontrolled arrhythmia, or hypertension; history of labile hypertension or poor compliance with an antihypertensive regimen). 4. Uncontrolled active severe systemic infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to C1D1. 5. Patients with known symptomatic brain metastasis are not suitable for enrollment. Patients with asymptomatic, stable, treated brain metastases are eligible for study entry. 6. Patients with a known history of human immunodeficiency virus (HIV); HIV testing is not required as part of this study. 7. Known, active hepatitis A, B, or C infection; or known to be positive for HCV RNA or HBsAg (HBV surface antigen). 8. Prior malignancy is not an exclusion. 9. Patients with gastrointestinal tract disease (or uncontrolled vomiting or diarrhea) that could interfere with the absorption of eltanexor. 10. Serious psychiatric or medical conditions that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give consent. 11. Patients unwilling to comply with the protocol including required biopsies and sample collections required to measure disease. 12. IPSS-R very low or low-risk MDS. 13. Evidence of transformation to AML by the World Health Organization (WHO) (=20% blasts in bone marrow or peripheral blood). 14. Patients receiving granulocyte-colony stimulating factor (G-CSF) or granulocyte macrophage-colony stimulating factor (GM-CSF) within the 2 weeks prior to C1D1. 15. Patients who demonstrate doubling of their bone marrow blast percentage within 4 weeks prior to Screening and have absolute blast percentage of > 15% at the time of Screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine overall response rate;Secondary Objective: To determine overall survival and 6-month overall survival To determine progression-free survival To determine disease control rate To determine duration of response To determine the rate of transfusion independence;Primary end point(s): To determine overall response rate;Timepoint(s) of evaluation of this end point: C2D1, C3D1, C5D1, D8D1 and EOT | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To determine overall survival and 6-month overall survival To determine progression-free survival To determine disease control rate To determine duration of response To determine the rate of transfusion independence;Timepoint(s) of evaluation of this end point: All other visits, except C2D1, C3D1, C5D1, D8D1 and EOT | — |
Countries
Canada, France, Italy, Spain, United States
Contacts
Public ContactClinical Trials Information Desk
Karyopharm Therapeutics Inc.
Outcome results
None listed