Patients with acute mieloyd leukemia (AML) MedDRA version: 20.1 Level: LLT Classification code 10024349 Term: Leukemia myeloid System Organ Class: 100000004864
Conditions
Interventions
Product Name: ORY-1001.2HCl
Product Code: PEI 13-106
Pharmaceutical Form: Oral solution
INN or Proposed INN: ORY-1001
CAS Number: 1431303-72-8
Other descriptive name: ORY-1001
Concentration unit: µg/m
Sponsors
Oryzon Genomics S. A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects = 60 years of age with AML according to World Health Organization (WHO) classification, who are considered by the investigator ineligible for intensive chemotherapy regimen at that time or have refused standard chemotherapy. 2. Blasts at least 20% of bone marrow and/or = 20 % in peripheral blood. 3. Subjects may not have received prior treatment for AML other than Hydroxyurea. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. 5. Platelets = 100 x10e9/ L without transfusion (in the opinion of the investigator). 6. Chemical laboratory parameters within the following range: a. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3x the upper limit of normal (ULN). b. Total bilirubin = 1.5 x the ULN; patients with Gilbert’s syndrome can enroll if conjugated bilirubin is within normal limits. 7. Patients with preserved renal function: serum creatinine = 1.5 mg /dl. 8. Patients must be capable of understanding and complying with protocol requirements, and they must be able and willing to sign a written informed consent, and willing to complete all scheduled visits and assessments at the institution administering. 9. Life expectancy of at least 3 months in the opinion of the investigator. 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 8 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 22
Exclusion criteria
Exclusion criteria: 1. Malignancies other than AML within 1 year prior to start treatment, except for those that are in complete remission, no treatment is required and with a minimal risk of metastasis or death, such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, ductal carcinoma in situ treated surgically with curative intent. 2. Patients with uncontrolled hypertension (in the opinion of the investigator). 3. Patients with uncontrolled diabetes (in the opinion of the investigator). 4. Active hepatitis C virus (HCV) or hepatitis B virus (HBV). Patients who are positive for hepatitis B core antibody, hepatitis B surface antigen, or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded. 5. Known positive test result for human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS). 6. Inter-current illness or social situation that will limit compliance with study requirements. Any serious underlying medical or psychiatric condition (e.g. alcohol or drug abuse), dementia or altered mental status or any issue that would impair the ability of the patient to understand informed consent or that in the opinion of the investigator would contraindicate the patient’s participation in the study or confound the results of the study. 7. A physical exam or laboratory finding that contraindicates the use of investigational therapy or otherwise places the patient at excessively high risk for treatment, as determined by the Investigator. 8. Patients medicated with anti-depressants reported to have KDM1A/LSD1 inhibitory activity: tranylcypromine or phenelzine. 9. History of central nervous system (CNS) disease involvement or prior history of NCI CTCAE Grade = 3 drug-related CNS toxicity. 10. Evidence of active uncontrolled viral, bacterial, or systemic fungal infection. Prophylactic therapy according to institutional protocols is acceptable. 11. Peripheral white blood cell (WBC) count = 20 x 10e9/L on Day 1 prior to treatment. Hydroxyurea or 6-mercaptopurine are allowed until 24 hours prior study treatment start. 12. Pregnant or lactating / breastfeeding women. 13. Fertile women of childbearing potential (WCBP) not willing to use double barrier methods of contraception (abstinence, oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly, or surgically sterile) during the trial and 90 days after the end of treatment. Male patients whose partners are not willing to use double-barrier methods of contraception.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To asses safety, tolerability and dose finding of ORY-1001 in combination with azacitidine.;Secondary Objective: -Time to response (time from the start of treatment with ORY-1001 to the first objective tumor response observed in terms of number of cycles administered) -Duration of response d(the time from the first occurrence of a documented objective response to the time of progression or death from any cause, whichever occurs first) -Objetive response (number of subjects achieving complete remission, CR with incomplete recovery, partial remission, confirmed by repeat assessments = 4 weeks after initial documentation) -Hematologic improvement (hematologic improvements of some cellular line that allow patient improve their quality of life) -Event–Free Survival (time from first study treatment to disease progression or death) -Overall Survival (the time from first study treatment to death from any cause) -To monitor ORY-1001 exposure and accumulation at steady state -To monitor ORY-1001 pharmacodynamics in terms of LSD1 target engagement in peripheral blood mononuclear cells;Primary end point(s): Dose finding, safety and tolerability of combo therapy.;Timepoint(s) of evaluation of this end point: until disease progression or unacceptable toxicities | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Time to first response (TTR) of combo therapy. 2. Duration of response (DOR) of combo therapy. 3. Objetive response (OR) of combo therapy. 4. Hematologic improvement (HI) of combo therapy. 5. Event – Free Survival (EFS) of combo therapy. 6. Overall Survival (OS) of combo therapy. 7. To monitor ORY-1001 pharmacokinetics (PK). 8. To monitor ORY-1001 pharmacodynamics (PD) in terms of LSD1 target engagement in peripheral blood mononuclear cells (PBMCs). Exploratory endpoints 1. Determination of gene expression changes in response to ORY-1001 for specific biomarkers. 2. Morphological differentiation observed in blasts in PB and BM.;Timepoint(s) of evaluation of this end point: until disease progression or unacceptable toxicities | — |
Countries
Spain
Contacts
Public ContactRoger Bullock
Oryzon Genomics S. A.
Outcome results
None listed