E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
relapsed/refractory (R/R) acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)
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E.1.1.1 | Medical condition in easily understood language |
Acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)
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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 | 10000880 |
E.1.2 | Term | Acute myeloid leukaemia |
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 | 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.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Investigating MP0533 as monotherapy in patients with R/R AML and MDS/AML is to: • Determine the safety and tolerability • Define the recommended phase 2 dose regimen (RP2D-R) and/or the maximum tolerated dose-regimen (MTD-R) (phase 1 only) • Evaluate the preliminary anti-leukemic activity (primary for phase 2a, secondary for phase 1) |
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E.2.2 | Secondary objectives of the trial |
Investigating MP0533 as monotherapy in patients with R/R AML and MDS/AML is to: • Further evaluate the preliminary anti-leukemic activity • Characterize the pharmacokinetics (PK) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Has signed and dated written informed consent prior to performing any study procedure, including screening 2. Diagnosis of AML or MDS/AML according to the ELN recommendation 2022 (Appendix 12.1 of the protocol), refractory or relapsed to pretreatment with hypomethylating agents (HMA) (with or without venetoclax), induction chemotherapy or allogeneic hematopoietic cell transplantation (HCT) 3. Age ≥18 years old on the day of signing informed consent 4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2 (see Appendix 12.2 of the protocol) 5. Anticipated life expectancy ≥ 12 weeks by investigator judgement 6. Adequate renal and hepatic function: a. Creatinine clearance > 40 mL/min on the basis of Cockcroft-Gault glomerular filtration rate estimation, unless considered AML- or MDS-related b. Serum bilirubin ≤ 2.5 x upper limit of normal (ULN), unless considered AML- or MDS-related or due to Gilbert’s syndrome c. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN, unless considered AML- or MDS-related 7. Is using highly effective contraception, for females of childbearing potential (FCBP) and for men |
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E.4 | Principal exclusion criteria |
1. Allogeneic HCT within the last 3 months 2. Active GvHD requiring immune-suppressive therapy (other than prednisone (or equivalent) ≤ 10mg/d) 3. Use of immunosuppressive drugs (other than prednisone (or equivalent) ≤10mg/d) in the past 4 weeks 4. Symptoms of leukostasis (prior hydroxyurea allowed) 5. Clinical signs of AML in the central nervous system 6. Major surgery within 28 days prior to start of study medication 7. Other malignancy requiring active therapy, but adjuvant endocrine therapy is allowed 8. Any active infection requiring the use of parenteral antimicrobial agents or that is grade >2 9. Treatment with agents targeting CD33, CD123 or CD70 within 4 weeks prior to start of trial medication 10. Left ventricular ejection fraction of < 50% on echocardiographic exam at screening 11. History or evidence of clinically significant cardiovascular disease 12. Pulmonary disease with clinically relevant hypoxia 13. Known Human Immunodeficiency Virus (HIV)-infected patients who are healthy and have a low risk of Acquired Immunodeficiency Syndrome (AIDS)-related outcomes may be eligible (see protocol) 14. Active hepatitis B (chronic or acute; HBV) 15. Active hepatitis C (HCV) infection 16. Any vaccines within 28 days before first study drug administration 17. History of another primary malignancy may be excluded (see protocol) |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Incidence of CRS and non-CRS DLTs during the first cycle of treatment (phase 1 only) - Type, incidence and severity of AEs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 - Changes in laboratory safety parameters and vital signs - Overall response rate (ORR) based on best overall response of complete remission, complete remission with partial hematological recovery (CRh); complete remission with incomplete hematological recovery (CRi), morphologic leukemia-free state (MLFS) and partial remission (PR) according to the European LeukemiaNet (ELN) response criteria 2022 (phase 2a only) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Variable. For example, certain assessments will be performed at screening, at week 4, 8 and 12 after the start of study treatment and every 12 weeks (± 1 week) thereafter until PD, withdrawal of consent, death, or study termination, whichever occurs first. |
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E.5.2 | Secondary end point(s) |
- Determination of PK parameters including (but not limited to) Cmax, time at Cmax (Tmax), minimal serum concentration (Cmin), area under the concentration-time curve (AUC), total CL, volume of distribution (Vd) and t1/2 - Different levels of CR, CRh, CRi, MLFS and PR according to the ELN response criteria 2022, separately and pooled - Event free survival (EFS) based on ELN response criteria 2022 - Duration of response (DoR) based on ELN response criteria 2022 - Overall survival (OS) (phase 2a only) - Reduction of granulocyte-colony stimulating factor (G-CSF) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
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.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
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 |
Switzerland |
France |
Germany |
Lithuania |
Netherlands |
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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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The overall EoS is defined as the date when the last patient/last visit occurs or when the last data point required for statistical analysis or safety FU is received from the last patient, whichever occurs later. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |