Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 16

Search results for: Gozde Inal Kiziltepe

16 Numerical Board Game for Low-Income Preschoolers

Authors: Gozde Inal Kiziltepe, Ozgun Uyanik

Abstract:

There is growing evidence that socioeconomic (SES)-related differences in mathematical knowledge primarily start in early childhood period. Preschoolers from low-income families are likely to perform substantially worse in mathematical knowledge than their counterparts from middle and higher income families. The differences are seen on a wide range of recognizing written numerals, counting, adding and subtracting, and comparing numerical magnitudes. Early differences in numerical knowledge have a permanent effect childrens’ mathematical knowledge in other grades. In this respect, analyzing the effect of number board game on the number knowledge of 48-60 month-old children from disadvantaged low-income families constitutes the main objective of the study. Participants were the 71 preschoolers from a childcare center which served low-income urban families. Children were randomly assigned to the number board condition or to the color board condition. The number board condition included 35 children and the color board game condition included 36 children. Both board games were 50 cm long and 30 cm high; had ‘The Great Race’ written across the top; and included 11 horizontally arranged, different colored squares of equal sizes with the leftmost square labeled ‘Start’. The numerical board had the numbers 1–10 in the rightmost 10 squares; the color board had different colors in those squares. A rabbit or a bear token were presented to children for selecting, and on each trial spun a spinner to determine whether the token would move one or two spaces. The number condition spinner had a ‘1’ half and a ‘2’ half; the color condition spinner had colors that matched the colors of the squares on the board. Children met one-on-one with an experimenter for four 15- to 20-min sessions within a 2-week period. In the first and fourth sessions, children were administered identical pretest and posttest measures of numerical knowledge. All children were presented three numerical tasks and one subtest presented in the following order: counting, numerical magnitude comparison, numerical identification and Count Objects – Circle Number Probe subtest of Early Numeracy Assessment. In addition, same numerical tasks and subtest were given as a follow-up test four weeks after the post-test administration. Findings obtained from the study; showed that there was a meaningful difference between scores of children who played a color board game in favor of children who played number board game.

Keywords: low income, numerical board game, numerical knowledge, preschool education

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15 The Thoughts and Feelings of 60-72 Month Old Children about School and Teacher

Authors: Ayse Ozturk Samur, Gozde Inal Kiziltepe

Abstract:

No matter what level of education it is, starting a school is an exciting process as it includes new experiences. In this process, child steps into a different environment and institution except from the family institution which he was born into and feels secure. That new environment is different from home; it is a social environment which has its own rules, and involves duties and responsibilities that should be fulfilled and new vital experiences. The children who have a positive attitude towards school and like school are more enthusiastic and eager to participate in classroom activities. Moreover, a close relationship with the teacher enables the child to have positive emotions and ideas about the teacher and school and helps children adapt to school easily. In this study, it is aimed to identify children’s perceptions of academic competence, attitudes towards school and ideas about their teachers. In accordance with the aim a mixed method that includes both qualitative and quantitative data collection methods are used. The study is supported with qualitative data after collecting quantitative data. The study group of the research consists of randomly chosen 250 children who are 60-72 month old and attending a preschool institution in a city center located West Anatolian region of Turkey. Quantitative data was collected using Feelings about School scale. The scale consists of 12 items and 4 dimensions; school, teacher, mathematic, and literacy. Reliability and validity study for the scale used in the study was conducted by the researchers with 318 children who were 60-72 months old. For content validity experts’ ideas were asked, for construct validity confirmatory factor analysis was utilized. Reliability of the scale was examined by calculating internal consistency coefficient (Cronbach alpha). At the end of the analyses it was found that FAS is a valid and reliable instrument to identify 60-72 month old children’ perception of their academic competency, attitude toward school and ideas about their teachers. For the qualitative dimension of the study, semi-structured interviews were done with 30 children aged 60-72 month. At the end of the study, it was identified that children’s’ perceptions of their academic competencies and attitudes towards school was medium-level and their ideas about their teachers were high. Based on the semi structured interviews done with children, it is identified that they have a positive perception of school and teacher. That means quantitatively gathered data is supported by qualitatively collected data.

Keywords: feelings, preschool education, school, teacher, thoughts

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14 Development of an Elastic Functionally Graded Interphase Model for the Micromechanics Response of Composites

Authors: Trevor Sabiston, Mohsen Mohammadi, Mohammed Cherkaoui, Kaan Inal

Abstract:

A new micromechanics framework is developed for long fibre reinforced composites using a single fibre surrounded by a functionally graded interphase and matrix as a representative unit cell. The unit cell is formulated to represent any number of aligned fibres by a single fibre. Using this model the elastic response of long fibre composites is predicted in all directions. The model is calibrated to experimental results and shows very good agreement in the elastic regime. The differences between the proposed model and existing models are discussed.

Keywords: computational mechanics, functionally graded interphase, long fibre composites, micromechanics

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13 Microbial Assessment of Fenugreek Paste during Storage and Antimicrobial Effect of Greek Clover, Trigonella foenum-graecum

Authors: Zerrin Erginkaya, Gözde Konuray

Abstract:

In this study, antimicrobial effect of Greek clover was determined with usage of MIC (minimum inhibition concentration) and agar diffusion method. Moreover, pH, water activity and microbial change were determined during storage of fenugreek paste. At first part of our study, microbial load of spices was evaluated. Two different fenugreek pastes were produced with mixing of Greek clover, spices, garlic and water. Fenugreek pastes were stored at 4 °C. At the second part, antimicrobial effect of Greek clover was determined on Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Debaryomyces hansenii, Aspergillus parasiticus, Candida rugosa, Mucor spp., when the concentrations of Greek clover were 8%, 12% and 16%. According to the results obtained, mould growth was determined at 15th and 30th days of storage in first and second fenugreek samples, respectively. Greek clover showed only antifungal effect on Aspergillus parasiticus at previously mentioned concentrations.

Keywords: antimicrobial, fenugreek, Greek clover, minimum inhibition concentration

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12 The Factors That Influence the Self-Sufficiency and the Self-Efficacy Levels among Oncology Patients

Authors: Esra Danaci, Tugba Kavalali Erdogan, Sevil Masat, Selin Keskin Kiziltepe, Tugba Cinarli, Zeliha Koc

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This study was conducted in a descriptive and cross-sectional manner to determine that factors that influence the self-efficacy and self-sufficiency levels among oncology patients. The research was conducted between January 24, 2017 and September 24, 2017 in the oncology and hematology departments of a university hospital in Turkey with 179 voluntary inpatients. The data were collected through the Self-Sufficiency/Self-Efficacy Scale and a 29-question survey, which was prepared in order to determine the sociodemographic and clinical properties of the patients. The Self-Sufficiency/Self-Efficacy Scale is a Likert-type scale with 23 articles. The scale scores range between 23 and 115. A high final score indicates a good self-sufficiency/self-efficacy perception for the individual. The data were analyzed using percentage analysis, one-way ANOVA, Mann Whitney U-test, Kruskal Wallis test and Tukey test. The demographic data of the subjects were as follows: 57.5% were male and 42.5% were female, 82.7% were married, 46.4% were primary school graduate, 36.3% were housewives, 19% were employed, 93.3% had social security, 52.5% had matching expenses and incomes, 49.2% lived in the center of the city. The mean age was 57.1±14.6. It was determined that 22.3% of the patients had lung cancer, 19.6% had leukemia, and 43.6% had a good overall condition. The mean self-sufficiency/self-efficacy score was 83,00 (41-115). It was determined that the patients' self-sufficiency/self-efficacy scores were influenced by some of their socio-demographic and clinical properties. This study has found that the patients had high self-sufficiency/self-efficacy scores. It is recommended that the nursing care plans should be developed to improve their self-sufficiency/self-efficacy levels in the light of the patients' sociodemographic and clinical properties.

Keywords: oncology, patient, self-efficacy, self-sufficiency

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11 Physicochemical and Microbiological Properties of Kefir, Kefir Yogurt and Chickpea Yogurt

Authors: Nuray Güzeler, Elif Ari, Gözde Konuray, Çağla Özbek

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The consumption of functional foods is very common. For this reason, many products which are probiotic, prebiotic, energy reduced and fat reduced are developed. In this research, physicochemical and microbiological properties of functional kefir, kefir yogurt and chickpea yogurt were examined. For this purpose, pH values, titration acidities, viscosity values, water holding capacities, serum separation values, acetaldehyde contents, tyrosine contents, the count of aerobic mesophilic bacteria, lactic acid bacteria count and mold-yeast counts were determined. As a result of performed analysis, the differences between titration acidities, serum separation values, water holding capacities, acetaldehyde and tyrosine contents of samples were statistically significant (p < 0.05). There were no significant differences on pH values, viscosities, and microbiological properties of samples (p > 0.05). Consequently industrial production of functional kefir yogurt and chickpea yogurt may be advised.

Keywords: chickpea yogurt, kefir, kefir yogurt, milk

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10 Natural Preservatives: An Alternative for Chemical Preservative Used in Foods

Authors: Zerrin Erginkaya, Gözde Konuray

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Microbial degradation of foods is defined as a decrease of food safety due to microorganism activity. Organic acids, sulfur dioxide, sulfide, nitrate, nitrite, dimethyl dicarbonate and several preservative gases have been used as chemical preservatives in foods as well as natural preservatives which are indigenous in foods. It is determined that usage of herbal preservatives such as blueberry, dried grape, prune, garlic, mustard, spices inhibited several microorganisms. Moreover, it is determined that animal origin preservatives such as whey, honey, lysosomes of duck egg and chicken egg, chitosan have antimicrobial effect. Other than indigenous antimicrobials in foods, antimicrobial agents produced by microorganisms could be used as natural preservatives. The antimicrobial feature of preservatives depends on the antimicrobial spectrum, chemical and physical features of material, concentration, mode of action, components of food, process conditions, and pH and storage temperature. In this review, studies about antimicrobial components which are indigenous in food (such as herbal and animal origin antimicrobial agents), antimicrobial materials synthesized by microorganisms, and their usage as an antimicrobial agent to preserve foods are discussed.

Keywords: animal origin preservatives, antimicrobial, chemical preservatives, herbal preservatives

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9 Qualitative Analysis of Emotional Thoughts in the Perspective of Nurses Who Have Been Working Experience in Pediatric Hematology-Oncology Unit

Authors: Sevil Inal, Leman Yantiri, Meral Kelleci

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Aim: In this study, it was aimed to qualitatively analyze the feelings, thoughts and meanings of the nurses who had experience in child hematology in the past. Method: In this qualitative study, in-depth interviews were conducted with 15 nurses between 29 and 53 years of age who had previously worked in child hematology-oncology unit. Interviews were conducted with a semi-structured interview form. Each interview lasted 20-30 minute. Some of the questions are: ‘What kind of experiences do you experience when you think about the periods you are working in hematology-oncology service?’ ‘Do you explain the reason for living these feelings?’ The data were analyzed with QSR NVivo 7 software. Results: From the perspective of the nurses who had experience working in the pediatric hematology-oncology service in the past, five main themes and sub-themes related to emotions and thoughts towards this experiment were identified in the study. 1) Positive and negative emotions: (a) fear and anxiety, (b) desperation, pity, guilt, (c) burnout, (d) longing; 2) Being coping 3) Professional implications 4) Meaning of life 5) Unmet needs and suggestions. Conclusions: Working in hematology should be viewed as a multidimensional situation that affects the way nurses view their profession and life, leading to a wide range of emotional lives. Data obtained from this study can be used to strengthen hematologic nurses.

Keywords: cancer, child, care, hematology, nursing

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8 Effects of Different Sowing Dates on Oil Yield of Castor (Ricinus communis L.)

Authors: Özden Öztürk, Gözde Pınar Gerem, Ayça Yenici, Burcu Haspolat

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Castor (Ricinus communis L.) is one of the important non-edible oilseed crops having immense industrial and medicinal value. Oil yield per unit area is the ultimate target in growing oilseed plants and sowing date is one of the important factors which have a clear role in the production of active substances particularly in oilseeds. This study was conducted to evaluate the effect of sowing date on the seed and oil yield of castor in Central Anatolia in Turkey in 2011. The field experiment was set up in a completely randomized block design with three replication. Black Diamond-2 castor cultivar was used as plant material. The treatment was four sowing dates of May 10, May 25, June 10, June 25. In this research; seed yield, oil content and oil yield were investigated. Results showed that the effect of different sowing dates was significant on all of the characteristics. In general; delayed sowing dates, resulted in decreased seed yield, oil content and oil yield. The highest value of seed yield, oil content and oil yield (respectively, 2523.7 kg ha-1, 51.18% and 1292.2 kg ha-1) were obtained from the first sowing date (May 10) while the lowest seed yield, oil content and oil yield (respectively, 1550 kg ha-1, 43.67%, 677.3 kg ha-1) were recorded from the latest sowing date (June 25). Therefore, it can be concluded that early May could be recommended as an appropriate sowing date in the studied location and similar climates for achieved high oil yield of castor.

Keywords: castor bean, Ricinus communis L., sowing date, seed yield, oil content

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7 Nucleotide Diversity and Bacterial Endosymbionts of the Black Cherry Aphid Myzus cerasi (Fabricus, 1775) (Hemiptera: Aphididae) from Turkey

Authors: Burcu Inal, Irfan Kandemir

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Sequences of mitochondrial cytochrome oxidase I (COI) gene of twenty-five Turkish and one Greek Myzus cerasi (Fabricus) (Hemiptera: Aphididae) in populations were collected from Prunus avium and Prunus cerasus. The partial coding region of COI studied is 605 bp for all the populations, from which 565 nucleotides were conserved, 40 were variable, 37 were singleton, and 3 sites were parsimony-informative. Four haplotypes were identified based on nucleotide substitutions, and the mean of intraspecific divergence was calculated to be 0.3%. Phylogenetic trees were constructed using Maximum Likelihood, Minimum Evolution, Neighbor-joining, and Unweighed Pair Group Method of Arithmetic Averages (UPGMA) and Myzus persicae (Sulzer) and Myzus borealis Ossiannilson were included as outgroups. The population of M. cerasi from Isparta diverged from the rest of the groups and formed a clade (Haplotype B) with Myzus borealis. The rest of the haplotype diversity includes Haplotype A and Haplotype C with individuals characterized as Myzus cerasi pruniavium and Haplotype D with Myzus cerasi cerasi. M. cerasi diverge into two subspecies and it must be reevaluated whether this pest is monophagous or oligophagous in terms of plant type dependence. The obligated endosymbiont Buchnera aphidicola was also found during this research, but no facultative symbionts could be found. It is expected further studies will be required for a complete barcoding and diversity of bacterial endosymbionts present.

Keywords: bacterial endosymbionts, barcoding, black cherry aphid, nucleotide diversity

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6 A Faunistic Study of Tetranychid and Phytoseiid Mites Associated with Diverse Crops From Samsun, Turkey

Authors: B. İnal, H. Di̇ler

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This research was implemented from March to September to reveal tetranychid and phytoseiid mites on different field crops in Samsun province, Turkey. In consequence of microscope slide-mounting of mite samples in Hoyer’s medium, a total of six species belonging to Tetranychidae and fourteen species belonging to Phytoseiidae were found. Tetranychus urticae Koch, Tetranychus turkestani Ugarov and Nikolski, Tetranychus viennensis Zacher, Panonychus ulmi (Koch), Panonychus citri (Mc Gregor) and Bryobia rubrioculus (Scheuten) were detected as phytophaous mites. Euseius finlandicus (Oudemans), Kampimodromus aberrans (Oudemans), Amblyseius agrestris (Karg), Amblyseius andersoni (Chant), Amblyseius bicaudus Wainstein, Amblyseius zwölferi (Dosse), Amblyseius barkeri (Hughes), Paraseilus soleiger (Ribaga), Anthoseius recki (Wainstein), Phytoseius finitimus Ribaga, Typhlodromus pyri Scheuten, Typhloctonus tiliarum Oudemans, Phytoseiulus macropilis (Banks) and Phytoseiulus persimilis Athias-Henriot were identified to be predatory mites in Phytoseiidae. Among the phytoseiid species Kampimodromus aberrans, Amblyseius andersoni, Anthoseius recki, Phytoseius finitimus, Phytoseiulus persimilis and Phytoseiulus macropilis were widespread. Relationship between tetranychid and phytoseiid mites on different crops that can make considerable contribution to biological control in integrated pest management (IPM) programs is also reported.

Keywords: biological control, IPM, interaction, phytoseiidae, tetranychidae

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5 Isolation and Molecular IdentıFıCation of Polyethylene Degrading Bacteria From Soil and Degradation Detection by FTIR Analysis

Authors: Morteza Haghi, Cigdem Yilmazbas, Ayse Zeynep Uysal, Melisa Tepedelen, Gozde Turkoz Bakirci

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Today, the increase in plastic waste accumulation is an inescapable consequence of environmental pollution; the disposal of these wastes has caused a significant problem. Variable methods have been utilized; however, biodegradation is the most environmentally friendly and low-cost method. Accordingly, the present study aimed to isolate the bacteria capable of biodegradation of plastics. In doing so, we applied the liquid carbon-free basal medium (LCFBM) prepared with deionized water for the isolation of bacterial species obtained from soil samples taken from the Izmir Menemen region. Isolates forming biofilms on plastic were selected and named (PLB3, PLF1, PLB1B) and subjected to a degradation test. FTIR analysis, 16s rDNA amplification, sequencing, identification of isolates were performed. Finally, at the end of the process, a mass loss of 16.6% in PLB3 isolate and 25% in PLF1 isolate was observed, while no mass loss was detected in PLB1B isolate. Only PLF1 and PLB1B created transparent zones on plastic texture. Considering the FTIR result, PLB3 changed plastic structure by 13.6% and PLF1 by 17%, while PLB1B did not change the plastic texture. According to the 16s rDNA sequence analysis, FLP1, PLB1B, and PLB3 isolates were identified as Streptomyces albogriseolus, Enterobacter cloacae, and Klebsiella pneumoniae, respectively.

Keywords: polyethylene, biodegradation, bacteria, 16s rDNA, FTIR

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4 An Assessment of Airport Collaborative Decision-Making System Using Predictive Maintenance

Authors: Faruk Aras, Melih Inal, Tansel Cinar

Abstract:

The coordination of airport staff especially in the operations and maintenance departments is important for the airport operation. As a result, this coordination will increase the efficiency in all operation. Therefore, a Collaborative Decision-Making (CDM) system targets on improving the overall productivity of all operations by optimizing the use of resources and improving the predictability of actions. Enlarged productivity can be of major benefit for all airport operations. It also increases cost-efficiency. This study explains how predictive maintenance using IoT (Internet of Things), predictive operations and the statistical data such as Mean Time To Failure (MTTF) improves airport terminal operations and utilize airport terminal equipment in collaboration with collaborative decision making system/Airport Operation Control Center (AOCC). Data generated by the predictive maintenance methods is retrieved and analyzed by maintenance managers to predict when a problem is about to occur. With that information, maintenance can be scheduled when needed. As an example, AOCC operator would have chance to assign a new gate that towards to this gate all the equipment such as travellator, elevator, escalator etc. are operational if the maintenance team is in collaboration with AOCC since maintenance team is aware of the health of the equipment because of predictive maintenance methods. Applying predictive maintenance methods based on analyzing the health of airport terminal equipment dramatically reduces the risk of downtime by on time repairs. We can classify the categories as high priority calls for urgent repair action, as medium priority requires repair at the earliest opportunity, and low priority allows maintenance to be scheduled when convenient. In all cases, identifying potential problems early resulted in better allocation airport terminal resources by AOCC.

Keywords: airport, predictive maintenance, collaborative decision-making system, Airport Operation Control Center (AOCC)

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3 Analyzing the Street Pattern Characteristics on Young People’s Choice to Walk or Not: A Study Based on Accelerometer and Global Positioning Systems Data

Authors: Ebru Cubukcu, Gozde Eksioglu Cetintahra, Burcin Hepguzel Hatip, Mert Cubukcu

Abstract:

Obesity and overweight cause serious health problems. Public and private organizations aim to encourage walking in various ways in order to cope with the problem of obesity and overweight. This study aims to understand how the spatial characteristics of urban street pattern, connectivity and complexity influence young people’s choice to walk or not. 185 public university students in Izmir, the third largest city in Turkey, participated in the study. Each participant had worn an accelerometer and a global positioning (GPS) device for a week. The accelerometer device records data on the intensity of the participant’s activity at a specified time interval, and the GPS device on the activities’ locations. Combining the two datasets, activity maps are derived. These maps are then used to differentiate the participants’ walk trips and motor vehicle trips. Given that, the frequency of walk and motor vehicle trips are calculated at the street segment level, and the street segments are then categorized into two as ‘preferred by pedestrians’ and ‘preferred by motor vehicles’. Graph Theory-based accessibility indices are calculated to quantify the spatial characteristics of the streets in the sample. Six different indices are used: (I) edge density, (II) edge sinuosity, (III) eta index, (IV) node density, (V) order of a node, and (VI) beta index. T-tests show that the index values for the ‘preferred by pedestrians’ and ‘preferred by motor vehicles’ are significantly different. The findings indicate that the spatial characteristics of the street network have a measurable effect on young people’s choice to walk or not. Policy implications are discussed. This study is funded by the Scientific and Technological Research Council of Turkey, Project No: 116K358.

Keywords: graph theory, walkability, accessibility, street network

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2 The Role of Dynamic Ankle Foot Orthosis on Temporo-Spatial Parameters of Gait and Balance in Patients with Hereditary Spastic Paraparesis: Six-Months Follow Up

Authors: Suat Erel, Gozde Gur

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Background: Recently a supramalleolar type of dynamic ankle foot orthosis (DAFO) has been increasingly used to support all of the dynamic arches of the foot and redistribute the pressure under the plantar surface of the foot to reduce the muscle tone. DAFO helps to maintain balance and postural control by providing stability and proprioceptive feedback in children with disease like Cerebral Palsy, Muscular Dystrophies, Down syndrome, and congenital hypotonia. Aim: The aim of this study was to investigate the role of Dynamic ankle foot orthosis (DAFO) on temporo-spatial parameters of gait and balance in three children with hereditary spastic paraparesis (HSP). Material Method: 13, 14, and 8 years old three children with HSP were included in the study. To provide correction on weight bearing and to improve gait, DAFO was made. Lower extremity spasticity (including gastocnemius, hamstrings and hip adductor muscles) using modified Ashworth Scale (MAS) (0-5), The temporo-spatial gait parameters (walking speed, cadence, base of support, step length) and Timed Up & Go test (TUG) were evaluated. All of the assessments about gait were compared with (with DAFO and shoes) and without DAFO (with shoes only) situations. Also after six months follow up period, assessments were repeated by the same physical therapist. Results: MAS scores for lower extremity were between “2-3” for the first child, “0-2” for the second child and “1-2” for the third child. TUG scores (sec) decreased from 20.2 to 18 for case one, from 9.4 to 9 for case two and from 12,4 to 12 for case three in the condition with shoes only and also from 15,2 to 14 for case one, from 7,2 to 7,1 for case two and from 10 to 7,3 for case three in the condition with DAFO and shoes. Gait speed (m/sec) while wearing shoes only was similar but while wearing DAFO and shoes increased from 0,4 to 0,5 for case one, from 1,5 to 1,6 for case two and from 1,0 to 1,2 for case three. Base of support scores (cm) wearing shoes only decreased from 18,5 to 14 for case one, from 13 to 12 for case three and were similar as 11 for case two. While wearing DAFO and shoes, base of support decreased from 10 to 9 for case one, from 11,5 to 10 for case three and was similar as 8 for case two. Conclusion: The use of a DAFO in a patient with HSP normalized the temporo-spatial gait parameters and improved balance. Walking speed is a gold standard for evaluating gait quality. With the use of DAFO, walking speed increased in this three children with HSP. With DAFO, better TUG scores shows that functional ambulation improved. Reduction in base of support and more symmetrical step lengths with DAFO indicated better balance. These encouraging results warrant further study on wider series.

Keywords: dynamic ankle foot orthosis, gait, hereditary spastic paraparesis, balance in patient

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1 MANIFEST-2, a Global, Phase 3, Randomized, Double-Blind, Active-Control Study of Pelabresib (CPI-0610) and Ruxolitinib vs. Placebo and Ruxolitinib in JAK Inhibitor-Naïve Myelofibrosis Patients

Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

Abstract:

Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

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