E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Refractory or Relapsed acute leukaemia (AL) |
Leucemia aguda (LA) recurrente o refractaria |
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E.1.1.1 | Medical condition in easily understood language |
Cancer of blood and bone marrow after treatment or remission |
Cáncer de la sangre y la médula ósea después del tratamiento o remisión |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000835 |
E.1.2 | Term | Acute leukemia |
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 | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024330 |
E.1.2 | Term | Leukemia acute |
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 | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024329 |
E.1.2 | Term | Leukemia |
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 | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10000830 |
E.1.2 | Term | Acute leukaemia |
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 |
Evaluate the safety (hematological and non-hematological toxicities) and tolerability of ORY-1001 |
Evaluar la seguridad y tolerabilidad de ORY-1001 en humanos |
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E.2.2 | Secondary objectives of the trial |
- Characterize the PK of orally administered ORY-1001 in patients with relapsed / refractory AL - Assess responses (CR/CRi/PR) with ORY-1001 in patients with relapsed or refractory AL, particularly in those with rMLL gene - Evaluate surrogate PD markers for target engagement |
- Describir la farmacocinética (FC) de ORY-1001 en humanos - Valorar las respuestas (RC/RCi/RP) con ORY-1001 en pacientes con leucemia aguda (LA) recurrente o refractaria, especialmente en aquellos que presentan el gen rMLL - Evaluar los marcadores de farmacodinámica (PD) indirectos para la unión de fármaco a su diana |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients aged 16 and above. 2. Patients must have relapsed or refractory AL (exluding promyelocytic leukaemia) considered by the investigator ineligible for intensive chemotherapy regimen at that time 3. Patients must have ECOG Performance Status (PS) of 0-2 4. Women of child-bearing potential must have negative serum or urine pregnancy test within two weeks prior treatment start 5. Fertile male or female patients must use highly efficient contraception for the duration of the study and 6 months after the last ORY-1001 dose. 6. Male patients must use condoms to avoid drug exposure of their partner. 7. Patients must be capable of understanding and complying with protocol requirements, and they must be able and willing to sign a written informed consent 8. Life expectancy of at least 2 months |
1. Pacientes con edad a partir de 16 años 2. Leucemia aguda (LA) recurrente o refractaria (sin incluir la leucemia promielocítica) que el investigador considere no apta para el régimen quimioterápico intensivo en ese momento 3. Escala de estado funcional (EF) ECOG de 0-2 4. Las mujeres en edad fértil deben presentar una prueba de embarazo en suero u orina negativa dentro de las dos semanas antes del inicio del tratamiento 5. Los pacientes hombres o mujeres fértiles deben usar un método anticonceptivo altamente eficaz durante el período de estudio y 6 meses después de la última dosis de ORY-1001. 6. Los pacientes hombres deben utilizar preservativo con el fin de evitar exponer a su pareja al fármaco. 7. Los pacientes deben poder entender y cumplir con los requisitos que establece el protocolo, y deberán ser capaces de y estar dispuestos a firmar un consentimiento informado por escrito 8. La esperanza de vida es de al menos 2 meses |
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E.4 | Principal exclusion criteria |
1. Cancer history that according to the investigator might confound the assessment of the study endpoints 2. Patients with uncontrolled hypertension or diabetes, hepatitis or HIV. 3. Inter-current illness or social situation that will limit compliance with study requirements 4. Pregnancy or lactating / breast feeding 5. Any medical condition which in the opinion of the investigator places the patient at an unacceptably high risk for toxicities if entered into the clinical study 6. Acute myeloid leukaemia treatment within the previous 14 days. Hydroxyurea or 6-mercaptopurine are allowed until 12 hours prior study treatment start and after the first treatment block (day 1-5) in case of hyperleucocytosis. 7. Patients medicated with anti-depressants reported to have KDM1A/LSD1 inhibitory activity: Tranylcypromine or Phenelzine. 8. Radiotherapy less than 2 weeks prior to the start of the study |
1. Antecedentes de cáncer que, según la opinión del investigador, puedan crear confusión en la evaluación de los criterios de valoración del estudio 2. Pacientes con hipertensión o diabetes insuficientemente controladas, hepatitis o VIH. 3. Patología intercurrente o situación social que pueda afectar al cumplimiento de los requisitos del estudio 4. Pacientes embarazadas o en período de lactancia 5. Cualquier afección médica que, en opinión del investigador, ponga al paciente en una situación inaceptable de alto riesgo de toxicidad al participar en el estudio clínico 6. Tratamiento de leucemia mieloide aguda recibido en los 14 días anteriores. La hidroxiurea o la 6-mercaptopurina están permitidas hasta 12 horas antes del inicio del tratamiento del estudio y tras la primera parte del tratamiento (días 1-5) en caso de hiperleucocitosis. 7. Los pacientes tratados con antidepresivos informaron una actividad inhibitoria KDM1A/LSD1: Tranilcipromina o fenelzina. 8. Radioterapia aplicada menos de 2 semanas antes del inicio del estudio |
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E.5 End points |
E.5.1 | Primary end point(s) |
The PK of ORY-1001 in patients with relapsed /refractory AL The PD of ORY-1001 in patients with relapsed / refractory AL Assess maximum tolerated dose of ORY-1001 in humans as a monotherapy Adverse events assessed by patient reporting Clinical observations and vital signs ECG Laboratory data |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Patients are to attend study centre visits during baseline (within 14 days before the first dose) and at defined days after start of treatment. Assessments will be made at baseline, day 1, 2, 3, 4, 5, 6, 7 of the first treatment block and on the first, third and fifth day of administration for the 3 other treatment blocks in the 28 day cycle. Additional visits may be made for safety reasons. Hematology samples (5ml) will be obtained on the first, third and fifth day of each treatment block. Samples for the analysis of blood chemistry (5ml) will be obtained weekly on the first day of each treatment block. A follow up visit will be performed at a minimum of 30 days after the last ORY-1001 dose. |
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E.5.2 | Secondary end point(s) |
Remission rate (CR + CRi) Gene expression changes in blood cells |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
DAY1: 0h (pre-dosing)2h, 4h, 6h, 8h, 12h, 18h DAY2: 24h, 28h, DAY3: 48h, 52h, DAY4: 72h, 76h, DAY5: 96h,100h, During the next 3 treatment blocks in the first cycle, samples will be taken only on the first day and the fifth day, just prior to administration |
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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 | 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 | Yes |
E.7.1.3.1 | Other trial type description |
dose escalation followed by an extension cohort at the MTD |
escalado de dosis seguida de un cohorte de extensión a la DMT |
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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 | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 7 |