A study to compare efficacy of PF 114 versus imatinib in the treatment of cancer.
- Conditions
- Health Condition 1: C00-D49- Neoplasms
- Registration Number
- CTRI/2022/06/043337
- Lead Sponsor
- JSC PHARMASYNTEZNORD
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Closed to Recruitment of Participants
- Sex
- Not specified
- Target Recruitment
- 0
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: - 100 x 109 platelets/L in peripheral blood, - 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 = 1.5 x ULN (upper limit of normal);
9. Satisfactory liver function according to the following criteria:
• Serum total bilirubin = 1,5 x ULN except for patients diagnosed with Gilbert’s syndrome; • Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2,5 x ULN;
• Alkaline phosphatase = 2,5 x ULN; • INR = 1,5 x ULN;
10. Satisfactory heart function, i.e. left ventricular ejection fraction above 40% according to echocardiography
11. QTcF interval = 450 ms for men and = 470 ms for women during ECG assessment at screening;
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;
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 investigator’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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To prove the superiority of PF-114 over imatinib at a daily dose of 600 and 800 <br/ ><br>mg in the rate of achieving major molecular response (MMR) by 12 months of treatment and <br/ ><br>To obtain sufficient information about the benefits and risks of PF-114 <br/ ><br>to allow the authorized regulatory authorities to approve the medical use of PF-114 in adult <br/ ><br>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 Outcome Measures
Name Time Method Molecular response: the level of BCR-ABL1 transcripts =1% by <br/ ><br>6 months of therapy. <br/ ><br>• Molecular response 4 (MR4) by 12 months of treatment. <br/ ><br>• Molecular response 4.5 (MR4.5) by 12 months of treatment. <br/ ><br>• Progression-free or failure-free survival by 12 months ofTimepoint: Complete cytogenetic response (CCR) by 12 months of therapy. <br/ ><br>• Quality of life score (EQ-5D, Fact-Leu) by 12 months. <br/ ><br>• Progression-free or failure-free survival. <br/ ><br>• Progression-free survival. <br/ ><br>• Overall survival