Study title
Dose-finding Study to Evaluate the Tolerability, Safety, Pharmacokinetics and Preliminary Efficacy of PF-114 in Adult Ph+ CML Patients Resistant to 2nd Generation TKI or Presenting T315I Mutation [Russia]
Scientific title
A Multicenter, Open Label Cohort Phase 1 Dose Finding Study to Evaluate Tolerability, Safety, Pharmacokinetics and Preliminary Efficacy of PF-114 Mesylate for Oral Administration in Adult Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myeloid Leukemia (CML), Which is Resistant to the 2-nd Generation Bcr-Abl Inhibitors or Has T315I Mutation in the BCR-ABL Gene
(Clinicaltrials.gov No. NCT02885766)
Indication and most important inclusion criteria
Male or female patients 18 years of age or older with Ph+ CML in chronic phase (CP) or accelerated phase (AP) according to European LeukemiaNet guidelines (2013) can be considered for inclusion if they are intolerant to approved Bcr-Abl inhibitors or have not responded to previous treatment with at least one 2nd generation inhibitor of Bcr-Abl (dasatinib or nilotinib or bosutinib) or if they present T315I mutation in the BCR-ABL gene. In case of previous history of blast crisis phase of CML at least 6 months must have passed after the end of blast crisis phase and intake of the first dose of PF-114. To be included, patients need to have an ECOG performance status below or equal to 2 and adequate kidney, liver and heart function.
Short description of intervention
In this dose-finding study, PF-114 will be given by mouth, starting with a dose of 50 mg once daily in the first patient group. In the next patient groups, the dose is gradually increased up to 400 mg/day. The dose can be increased further based on the assessment of the safety findings by the investigators and the sponsor.
Type of study
Trial after therapy failure or intolerance
Current status
No longer recruiting. Interim results available.
Study sponsor
Fusion Pharma LLC
Scientific lead / contact
Veronika Shulgina MD, PhD
+7 916 815 05 44
Principal investigator
1. Prof. DMSci Anna Turkina
2. Elza Lomaia MD, PhD
Additional information
Study description in the US register ClinicalTrials.gov, a service of the U. S. National Institutes of Health
Study centers / principal investigators
Moscow
National Research Center for Hematology
Russia, 125 167, Moscow, Novii Zikovskii pr., 4
Principal Investigator:
Prof. DMSci Anna Turkina — Head of Myeloproliferative diseases
Clinical Study Coordinator:
Oleg Shuhov MD, PhD
+7 985 287 12 69
Moscow
Moscow City Centre of Hematology based on City Hospital named by S.Botkin
5, 2-nd Botkin's lane, build. 17, entrance 3
125284 Moscow
Principal Investigator:
Prof. DMSci Olga Vinogradova — Head of Moscow City Centre of Hematology
tel. +7(495)945-97-61
St. Petersburg
Federal Almazov North-West Medical Research Centre
Russia, 197 341, St. Petersburg, Akkuratova st., 2
Principal Investigator:
Elza Lomaia MD, PhD, — lead scientist of Onco-hematology Department
+7 981 936 16 67
Chronic Myeloid Leukemia
also called: Chronic Myelogeneous Leukemia
A chronic disease of the blood and bone marrow that results from a transformation of a stem cell.
Philadelphia chromosome
A certain change in chromosomes (on chromosome 22) found in 95% of patients who have CML. The Philadelphia chromosome results from a mutation that involves the fusion of parts of chromosome 9 and chromosome 22 (the bcr-abl fusion gene)
Inclusion criteria
Inlusion criteria define which subjects may participate in a clinical study. Study subjects must fulfill all inclusion criteria (e.g. with regard to sex, age, previous diseases). This ensures a uniform composition of the study population and minimizes the risk of influences that distort the study results.
Accelerated Phase
A phase of development of Chronic Myeloid Leukemia between chronic and blast phase. Untreated, the accelerated phase progresses to blast phase within a few months.
Chronic phase
The earliest phase of CML development.
Blast crisis
The third phase of development of CML after chronic and accelerated phases. It is characterized by the presence of increasing numbers of immature blood cells ("blasts") in the blood and bone marrow.
Chromosome
A chromosome is a structure of DNA that carries the genetic makeup in the nucleus of the cell. Chromosomes contain giant chain molecules of DNA, coiled and folded as aggregates with specific proteins. Chromosomes ensure that during cell division the hereditary information is evenly distributed to the daughter cells. Normal human body cells have 46 chromosomes. Cancer cells can have a different number and/or structure of chromosomes.
Indication
In medicine, a reason to use a certain diagnostic test, therapeutic procedure or medication. The opposite of indication is contraindication.
Bosutinib
Bosutinib (development name SKI-606, trade name Bosulif), a second generation tyrosine kinase inhibitor.
Also called Bosulif|SKI-606|SKI606
Dasatinib
Trade name: Sprycel, development name: BMS-354825, inhibits BCR-ABL and SRC tyrosine kinases. Authorized for marketing in the EU since 2006 for the treatment of CML and Ph+ALL.
Other names: BMS-354825|BMS354825|Sprycel
Nilotinib
Trade name: Tasigna, development name: AMN107, inhibits BCR-ABL tyrosine kinase. Authorized for marketing in the EU since 2007 for the treatment of CML and Ph+ALL.
Other names: |AMN107|Tasigna
BCR-ABL
The abnormal gene that characterizes Chronic Myeloid Leukemia, which is a fusion of the BCR gene of chromosome 9 and the ABL gene of chromosome 22
Chronic
Long-lasting, slowly developping
Blast
An immature white blood cell that normally represents an early phase of the development process of a blood stem cell in the bone marrow
Onco-
Part of the term oncology (study and science dealing with cancer).
ECOG
Eastern Cooperative Oncology Group Index to classify the quality of life of cancer patients on a scale ranging from 0 (fully active, able to carry on all predisease activities without restriction) to 5 (death).
Also often referred to as ECOG performance status.
Gene
A unit of information present as DNA; a gene usually contains the blueprint for a protein.
Oral
Oral, pertaining to the mouth; taken through or applied in the mouth.
CML
Chronic Myeloid Leukemia, also called Chronic Myelogenous Leukemia
A chronic disease of the blood and bone marrow that results from a transformation of a stem cell.
Ph+
Abbreviation for "Philadelphia-Chromosome-positive", meaning the presence of a certain change in chromosomes (on chromosome 22) found in 95% of patients who have CML. The Philadelphia chromosome results from a mutation that involves the fusion of parts of chromosome 9 and chromosome 22 (the bcr-abl fusion gene).
CHR
Abbreviation for Complete Hematologic Response. The blood cell count has returned to normal, and tests don’t show any immature white blood cells. Also, the spleen has returned to a normal size if it was enlarged.
