Phase 1/2 Open-Label Study of the Safety, Tolerability and overall effect ofEltanexor (KPT-8602) in Patients with high risk non-responsiveMyelodysplastic Syndrome (MDS)
- Conditions
- High-risk primary refractory MDS patientsTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-003810-38-IT
- Lead Sponsor
- KARYOPHARM THERAPEUTICS, INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 83
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 progressed 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 <2.
11. Prior to enrolling a patient with imminent risk of AML transformation (per opinion of the Investigator) or for patients with RAEB-2 MDS, the Medical Monitor must be contacted.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 21
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 83
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 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method