Acute myeloid leukaemia (AML), Chronic myelomonocytic leukaemia (CMML) and Myelodysplastic syndrome (MDS) MedDRA version: 21.1 Level: PT Classification code 10000880 Term: Acute myeloid leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) 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 versi
Conditions
Interventions
Product Name: EP0042_20mg
Pharmaceutical Form: Capsule
Current Sponsor code: EP0042
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Product Name: EP0042_50mg
Sponsors
Ellipses Pharma Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients aged = 18 years of age, at the time of informed consent, with histological or cytological confirmation of an advanced malignancy 2. Ability to understand and provide written informed consent before any study-specific procedures, sampling, or analyses, including access to archival tumour tissue 3. Ability to swallow and retain oral medication 4. Sufficient life expectancy to allow the patient to complete at least 1 cycle (28 days) of the treatment period. 5. ECOG Performance Status of 0, 1 or 2 at Screening 6. In the opinion of the investigator, all other relevant medical conditions must be well-managed and stable for at least 28 days prior to first administration of study drug Part A (escalation phase) only: 7. Patients with pathologically confirmed/documented AML or MDS, as defined by the 2017 European LeukaemiaNet (ELN) recommendations, or CMML, as defined by World Health Organization (WHO) criteria, who have relapsed from or are refractory to previous therapy. Part B (Expansion cohort patients) only: 8. Patients with pathologically confirmed/documented AML, as defined by the 2017 European LeukaemiaNet (ELN) recommendations, who either decline or are unsuitable for standard therapy, or who are refractory to, or have relapsed after, initial treatment, with no more than 3 prior lines of therapy Contraception (See Section 6.6) 9. Female patients should either be of non-child-bearing potential or must agree to use highly effective methods of contraception from Screening until 6 months following administration of the last dose of study drug 10. Male patients must use double barrier contraception from enrolment through treatment and for 6 months following administration of the last dose of study drug Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 43
Exclusion criteria
Exclusion criteria: Disease Under Study and Prior Anticancer Treatment 1. Suspected brain and/or leptomeningeal metastases that are symptomatic or untreated or that require current therapy 2. Acute promyelocytic leukaemia (FAB:M3) 3. Systemic anti-cancer therapy for the disease under study within 4 weeks of the first dose of study treatment. (Concomitant hydroxyurea is acceptable and will be permitted throughout the screening period and during first 2 cycles of study treatment) 4. Ongoing toxic manifestations of previous treatments that have not reduced to at least CTCAE Grade 1. Exceptions to this are alopecia or certain Grade 2 treatment related toxicities, which in the opinion of the Investigator should not exclude the patient. 5. Transplantation (allogeneic or autologous) within last 90 days, or on active immunosuppressive therapy for graft versus host disease in last 2 weeks Laboratory Parameters 6. Patient with any out-of-range laboratory values defined as shown below. Haematology evaluations must be performed =7 days from any blood or blood product transfusion and =14 days from any dose of hematologic growth factor. • Serum creatinine > 1.5 x upper limit of normal (ULN) and/or creatinine clearance (calculated using Cockcroft-Gault formula, or measured) 470 msec on screening ECG or congenital long QT syndrome 9. Receiving an investigational anti-cancer treatment concurrently or within 14 days or five half-lives of either the parent drug or any active metabolite prior to the start of treatment with EP0042. Patients may receive hydroxyurea throughout the screening period and during the first 2 cycles of study treatment. 10. Any evidence of severe or uncontrolled systemic or current unstable or uncompensated respiratory or cardiac conditions which makes it undesirable for the patient to participate in the study or which could jeopardize patient safety 11. Current refractory nausea and vomiting, malabsorption syndrome, disease significantly affecting gastrointestinal (GI) function, re-section of the stomach, extensive small bowel re-section that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery such as gastric bypass. 12. Known history of human immunodeficiency virus infection (HIV) (testing is not required), ctive hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Testing for HBV or HCV status is not necessary unless clinically indicated or the patient has a history of HBV or HCV infection 13. Hypersensitivity to EP0042 or D -a-Tocopherol polyethylene glycol succinate (TPGS) 14. Malignant disease other than that being treated in this study, with the following exceptions: • Malignancies that were treated curatively and have not recurred within 2 years prior to study treatment • Completely resected basal cell and squamous cell skin cancers • Any malignancy considered to be indolent and that has never required therapy • Completely resected carcinoma in situ of any type 15. Any medical condition that would, in the investigator’s judgment, prevent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the safety and tolerability of EP0042 given as a monotherapy in patients with relapsed or refractory AML (AML, MDS or CMML for Part A only) ;Secondary Objective: - To characterise the pharmacokinetics (PK) of EP0042, given as a monotherapy, after a single dose and at steady state after multiple dosing. -To assess the efficacy of EP0042, given as a monotherapy in patients with relapsed or refractory AML (and MDS or CMML for Part A only).;Primary end point(s): Incidence of dose-limiting toxicities (DLT), adverse events, serious adverse events and changes in laboratory parameters, physical examination, vital signs and electrocardiograms. ;Timepoint(s) of evaluation of this end point: DLTs, AEs and SAEs are evaluated from consent to 30 days after last study dose. Haematological Safety laboratory measurements are taken at every visit while on treatment and at follow up. Chemistry and Coagulation Safety Laboratory measurements are taken at every visit in Cycle 1 and every other visit (Days 1 and 15) while on treatment cycles and at follow up. Physical examinations are carried out every visit in Cycle 1 then on Day 1 of every other cycle while on treatment and at follow up. Vitial signs are taken at every visit in Cycle 1 and every other visit (Days 1 and 15) while on treatment cycles and at follow up. ECGs are are taken at every visit in Cycle 1 and Days 1 and 15 at Cycle 2. Then every cycle after cycle 2 on Day 1 while on treatment and during | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Plasma PK parameters (AUClast, AUCinf, Cmax and/or Cmin, Tmax, t1/2, CL/F, V/F and/or Vz/F) after single and multiple doses. Best Overall Response Duration of Response (DOR) ;Timepoint(s) of evaluation of this end point: Blood samples for PK analyses will be taken Cycle 1 Day 1 Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24-hours post dose. Samples also taken on Cycle 1 Day 8, 15 and 22 (to be taken pre-dose, or during the visit if no dose is administered) and Cycle 2 Day 1 pre-dose. If patient is completing Cycle 0 they will have an additional 3 draws on day 1 of treatment. Best Overall Response and Duration of Response will be calculated on the response criteria given at day 1 of each cycle from cycle 2 onwards. | — |
Countries
Australia, Netherlands, United Kingdom
Contacts
Public ContactHelen Bridger
Ellipses Pharma Limited
Outcome results
None listed