Health Condition 1: null- Relapsed/Refractory Hematologic Malignancies
Conditions
Interventions
Intervention1: P2745: Solid tablet dosage form for oral administration
2 dosage strengths: 75 and 400 mg per tablet.
400 mg/day to be administered to Cohort 1
Intervention2: P2745: P2745 will be prov
Sponsors
Piramal Life Sciences Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1. Male or female patients, of any race or ethnic group, of 18 years or more to less than 60 years of age. 2. Patients with a documented (histologically- or cytologically-proven), hematological malignancy that is relapsed or refractory to prior therapeutic regimens, and for whom no available standard therapeutic options that are anticipated to result in a durable remission. 3. Patients enrolled into DOSE ESCALATION COHORTS must have one of the following hematologic malignancies: Relapsed/refractory leukemias by WHO classification, including ALL, AML, CLL, CML, CMML Poor-risk myeoldysplastic syndrome (MDS) by WHO classification (i.e. RAEB-1 or RAEB-2) Myelofibrosis (MF) 4. Patients enrolled into the MTD EXPANSION COHORT must have CML in chronic or accelerated (but not blast) phase, and meet all other eligibility criteria. 5. Patients with an ECOG performance status of less than 2, and an anticipated life expectancy of 3 months and more 6. Patients able to take oral tablets 7. Patients, male and female, who are either not of childbearing potential or who agree to use a medically effective method of contraception during the study and for 1 month after the last dose of study drug 8. Patients with the ability to understand and give written informed consent.
Exclusion criteria
Exclusion criteria: 1. Patients with inadequate recovery from toxicity associated with any prior antineoplastic therapy (generally less than Grade 1 will be considered eligible) 2. Patients with CNS (or leptomeningeal) involvement by their disease or symptoms suggesting CNS involvement 3. Women who are pregnant or lactating 4. Patients with any of the following serum chemistry abnormalities: Total bilirubin higher than 1.5x the ULN unless considered due to Gilbert?s Syndrome AST or ALT more than 3x the ULN (more than 5x ULN if due to leukemic hepatic involvement). Serum creatinine more than 1.2x ULN (or a calculated creatinine clearance less than 60 mL/min/1.73 m2) 5. Patients with active, uncontrolled bleeding or with INR ULN for the institution 6. Patients with a significant cardiovascular disease or condition, including: Uncontrolled congestive heart failure defined as NYHA Class II to IV History of a clinically significant ventricular arrhythmia such as ventricular tachycardia, ventricular fibrillation, Torsades de pointes, or arrhythmias not controlled by medication, Diagnosed or suspected congenital or acquired prolonged QT syndrome; history of prolonged QTc interval; prolonged QTc interval (more than 0.45 sec) Unexplained syncope Uncontrolled hypertension within 3 months of study entry Symptomatic coronary heart disease (angina) Myocardial infarction within 12 months of study entry 7. Patients with significant gastrointestinal (GI) abnormalities, including: Prior surgical procedures affecting absorption; short bowel syndrome Malabsorption, GI bleeding within 1 month of study entry Vomiting or diarrhea of of more than 2 days duration within 2 weeks of study entry 8. Patients with treated or untreated graft versus host disease (GVHD) within 2 months of study entry 9. Patients with a history of allergic reactions attributable to compounds of similar chemical or biologic composition to P2745 (i.e., oxadiazole derivatives) 10. Patients with known seropositivity to HIV, known current acute or chronic Hepatitis B, known Hepatitis C (antigen positive), or hepatic cirrhosis 11. Patients with any other serious/active infection, or any infection requiring parenteral antibiotics 12. Patients with inadequate recovery from any prior surgical procedure, or patients having undergone any major surgical procedure within 4 weeks of study entry 13. Patients with any other life-threatening illness, significant organ system dysfunction, or clinically significant laboratory abnormality, which would either compromise the patient?s safety or interfere with evaluation of the safety of the study drug 14. Patients with a psychiatric disorder or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary studies 15. Patients with the inability to comply with the protocol requirements
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the safety, tolerability, dose-limiting toxicities (DLT), and maximally tolerated dose (MTD) of escalating doses of P2745Timepoint: MTD at the end of cycle 1 and will be assessed for MTD Throughout the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Disease Status AssessmentTimepoint: After every 2 cycles (or prior to start of the next cycle) End of Study 1 Month Follow-up As clinically indicated (in patients with hematologic response;Pharmacokinetics: Plasma Levels of P2745Timepoint: Cycle 1 Day 1 Pre-dose (within 30 minutes prior to dosing)30 min,1 h,2h,4h,6h,8h,12h,24h Day 8 and Day 15 Pre-dose (within 30 minutes prior to dosing), Day 21 Pre-dose,30 min,1h,2h,4h,6h,8h,12h,24h,36h 48h. Cycle 2 Day 1 Pre-dose Day 15 Pre-dose Subsequent Cycles Day 1 Pre-dose Day 15 Pre-dose End of Study ;To describe the preliminary antineoplastic activity of P2745Timepoint: Throughout the study;Urinary Metabolite(s) of P2745 Metabolite(s) (Optional)Timepoint: Cycle 1 Day 1 Pre-dose Day 21 0-4 h (after study drug administration) 4-24 h (ends prior to next dayâ??s dosing) 24-48 hours (if possible) | — |
Countries
India
Contacts
Public ContactDr Shivani Acharya
Piramal Life sciences limited
Outcome results
None listed