Health Condition 1: C00-D49- Neoplasms
Conditions
Interventions
Intervention1: PF-114 mesylate: PF-114 is administered daily at a dose of 300 mg, the interval between
doses should be approximately 24 hours (with a deviation of no more
than 2 hours). The investigat
Sponsors
JSC PHARMASYNTEZNORD
Eligibility
Inclusion criteria
Inclusion criteria: 1. The patient has given an informed consent to participate in this study; there is an informed consent form signed by the patient and the investigator; 2. Men and women aged 18 years old and over; 3. Confirmed diagnosis of Philadelphia chromosome positive chronic myeloid leukemia in the chronic phase according to the listed criteria of the European LeukemiaNet (ELN) Guidelines: â?? 100 x 109 platelets/L in peripheral blood, â?? Absence of clonal chromosomal abnormalities; 4. Resistance to imatinib treatment in a daily dose of 400 or 600 mg (see Appendix 6); 5. Patients previously not treated with any Bcr-Abl tyrosine kinase inhibitors other than imatinib, or duration of such drug treatment less than 1 week; 6. The presence of the standard BCR-ABL1 p210 transcript according to the data of the previous analysis; 7. Performance status according to Eastern United Oncological Group (ECOG) 0 to 1; 8. Satisfactory renal function, i.e. serum creatinine 9. Satisfactory liver function according to the following criteria: • Serum total bilirubin • Alkaline phosphatase 10. Satisfactory heart function, i.e. left ventricular ejection fraction above 40% according to echocardiography 11. QTcF interval 12. The consequences of previous therapy resolved to severity grade 1 or lower according to NCI CTC AE v5 (except for alopecia); 13. For women of childbearing potential, as well as men who have female partners of childbearing potential, consent to abstain from sexual intercourse or to use effective methods of contraception for the entire study period;
Exclusion criteria
Exclusion criteria: 1. Patients received imatinib therapy in a daily dose above 600 mg; 2. Patients with a major molecular response according to the results of the last test with molecular response assessment; 3. A history of imatinib intolerability, defined as the presence of grade 3 or 4 adverse reactions according to NCI CTC AE v5 during imatinib therapy, without satisfactory management with concomitant therapy or requiring imatinib dose reduction; 4. Presence of BCR-ABL1 mutations indicating high resistance to imatinib therapy: L248V, Q252R, Y253H/F, E255K/V, T315I/D, F317L, F486S; 5. Known intolerability of PF-114 components; 6. Use of the following previous treatment: a. chemotherapy drugs within 21 days before the first dose of the study drug (except for hydroxycarbamide, which does not require drug elimination from the body) or nitrosoureaderived drugs, as well as mitomycin C within 42 days before the first dose of the study drug; b. tyrosine kinase inhibitors, including approved and experimental drugs, within 4 days before the first dose of the study drug, except for imatinib in a constant daily dose of 400 mg or 600 mg for 2 or more weeks. Patient should not receive imatinib within 12 hours before the study drugs administration; c. radiation therapy within 28 days before the first dose of the study drug; d. autologous or allogeneic hematopoietic stem cell transplantation; e. herbal medicines within 2 weeks before the first PF-114 administration. The exception is cold medicines, if the patient takes them for no more than 7 days; f. potent inhibitors and potent inducers of CYP3A4 within 2 weeks before the study initiation. 7. Presence of clinically significant uncontrolled cardiovascular disease; 8. Uncontrolled arterial hypertension grade 2 or higher according to NCI CTC AE v5; 9. The patient is receiving drugs that are known to prolong the QT interval on the ECG only if they are not vital for the patient in the investigatorâ??s opinion; 10. Acute pancreatitis in medical history within 1 year before enrollment into the study, chronic pancreatitis or alcohol dependence; 11. Evidence of active graft versus host disease (GVHD) or GVHD requiring immunosuppressive therapy. Immunosuppressive therapy for prevention or treatment within 14 days before the first dose of PF-114; 12. Major surgery within 35 days; 13. Uncontrolled concomitant disease, including but not limited to the following: active systemic infection; uncontrolled seizure disorders; mental illnesses or social obstacles that prevent the patient from compliance with all the requirements of the protocol procedures or interfere with the study results; 14. Inability to swallow the drug, or gastrointestinal diseases that may adversely affect the absorption of PF-114 after oral administration; 15. History of other malignant tumors within the last 3 years (except for non-melanoma skin cancer, cervical cancer in situ). 16. Pregnancy or breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To prove the superiority of PF-114 over imatinib at a daily dose of 600 and 800 mg in the rate of achieving major molecular response (MMR) by 12 months of treatment and To obtain sufficient information about the benefits and risks of PF-114 to allow the authorized regulatory authorities to approve the medical use of PF-114 in adult patients with Ph+ CML in CP resistant to imatinib at standard daily doses of 400 or 600 mg.Timepoint: Major molecular response by 12 months of therapy (MMR 12) | — |
Secondary
| Measure | Time frame |
|---|---|
| Molecular response: the level of BCR-ABL1 transcripts â?¤1% by 6 months of therapy. â?¢ Molecular response 4 (MR4) by 12 months of treatment. â?¢ Molecular response 4.5 (MR4.5) by 12 months of treatment. â?¢ Progression-free or failure-free survival by 12 months ofTimepoint: Complete cytogenetic response (CCR) by 12 months of therapy. â?¢ Quality of life score (EQ-5D, Fact-Leu) by 12 months. â?¢ Progression-free or failure-free survival. â?¢ Progression-free survival. â?¢ Overall survival | — |
Countries
India, Kazakhstan, Pakistan, Russian Federation
Contacts
Public ContactDr Parvez A Kosgi
Edenwell Therapeutics Pvt. Ltd
Outcome results
None listed