E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
High-risk primary refractory MDS patients |
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E.1.1.1 | Medical condition in easily understood language |
High-risk primary refractory MDS patients |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028533 |
E.1.2 | Term | Myelodysplastic syndrome |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028535 |
E.1.2 | Term | Myelodysplastic syndrome unclassifiable |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028534 |
E.1.2 | Term | Myelodysplastic syndrome NOS |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067096 |
E.1.2 | Term | 5q minus myelodysplastic syndrome |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067387 |
E.1.2 | Term | Myelodysplastic syndrome transformation |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine overall response rate |
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E.2.2 | Secondary objectives of the trial |
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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 <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 |
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
To determine overall response rate |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
C2D1, C3D1, C5D1, D8D1 and EOT |
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E.5.2 | 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All other visits, except C2D1, C3D1, C5D1, D8D1 and EOT |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
United States |
France |
Spain |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |