Active clinical trials for "Leukemia, Lymphoid"

Acute lymphoblastic leukemia , also known as acute lymphocytic leukemia, characterized by the overproduction and accumulation of cancerous, immature white blood cells, known as lymphoblasts, causing damage and death by inhibiting the production of normal cells (such as red and white blood cells and platelets) in the bone marrow and by spreading (infiltrating) to other organs. Acute lymphoblastic leukemia is most common in childhood, with a peak incidence at 2-5 years of age and another peak in old age.

Using phage libraries extensively pre-absorbed on a series of normal cell types, we will isolate phage specifically internalized by B-CLL cells from newly diagnosed and untreated CLL patients. Peptide sequences are then derived by Next Generation Sequencing (NGS). NGS-based studies are contributing to an improved understanding of cancer heterogeneity in order to tailor treatment to patients based on the individual makeup of their tumor. However the use of NGS to derive phage displayed peptide sequences is so far rare (22). Traditionally, after exposure to a target and recovery by elution, the phage clones are isolated by titration on bacterial lawns. It is technically demanding and labour intensive to select and analyze more than about 15 of the sometimes thousands clones recovered. Therefore information on other potentially important sequences is missed. NGS allows sequencing of the entire recovered phage pool and provides far more detailed bioinformatic analyses of peptide sequences or motifs. RNA from the CLL cells is used for RNA-seq expression sequencing. The wide application of NGS in combination with bioinformatics tools has begun to revolutionize cancer research, diagnosis and therapy. The peptide and RNA sequencing data will afford bioinformatic testing of correlations of exome expression and clinical parameters with the pattern of peptide sequences internalized by CLL cells of different patients. This information is crucial to answering questions 1, 2 and 3 discussed on page 1 above. The results of this analysis will probably not allow identification of specific receptors targeted by the peptides. The aim at this stage of the research is to identify candidate targeting peptides. Once identified, further research will be needed to identify the receptors to which they bind. Regarding question 4, there is currently very little published information on the therapeutic potential of PDCs in leukemia. Using two peptides we have isolated that target murine A20 leukemic cells, we will prepare multi-drug PDCs (using technology we have developed) and in an animal model, test their ability to enhance the survival and quality of life of CLL bearing animals.

Acute lymphoblastic leukemia (ALL) is not a single disease, but a composite of heterogeneous subgroup. Accordingly, more sophisticated classification in ALL is essential to achieve further improvement of treatment outcomes. However, only a few genetic markers are revealed to have significant prognostic implications in ALL patients. The current study is designed to stratify the ALL patients according to their prognosis and to predict their outcomes by a pharmacogenetic approach. A predictive model will be generated from 130 genotypes in adult ALL patients diagnosed at the Samsung Medical Center (SMC), Sungkyunkwan University School of Medicine, Seoul,Korea between 1994 and 2008. The validation of the predictive model will be performed using an independent external cohort of ALL patients. Definition of the cohort: two hundred ALL patients from the SMC as a test set, another 100 patients from the SMC as a first validation set, and another 150 independent external patients as second external validation set. DNAs will be extracted and stored from patients' samples collected at the time of diagnosis. In the test set, genotypes will be determined using a MALDI-TOF based platform (Sequenom, San Diego, CA, USA) for 130 SNPs of the candidate genes involved in DNA repair pathway, drug metabolism/transport pathway and folate metabolism pathway. Bioinformatic analyses will be performed to identify around 13 genotypes (10%) having strongest predictive significance out of these 130 SNPs in terms of their treatment outcomes, drug toxicity and prognosis in the test set. These 13 genotypes will be validated in the first cohort of 100 ALL patients using a multivariate Cox's proportional hazard model. The predictive model will be built up based on Cox's proportional hazard model derived from 13 candidate genotypes and clinical risk factors. The predictive model based on pharmacogenetic information will be validated again in the second, independent external cohort of 150 ALL patients. Definite prognostic value was not established for genetic or molecular markers in acute lymphoblastic leukemia (ALL) except BCR/ABL fusion gene. The current study attempts to build up a predictive model based on single nucleotide polymorphisms (SNPs) with pharmacogenetic approach using 130 genotypes in the multiple candidate pathways such as DNA repair pathway, drug metabolism / transport pathway and folate metabolism pathway. The predictive model based on SNPs will be generated and validated with respect to treatment outcomes, drug toxicity and prognosis in adult ALL patients. The present study will demonstrate that: 1) Pharmacogenetic information derived from SNPs involved in the DNA repair pathway, drug metabolism/transport pathway and folate metabolism pathway, is helpful to predict the treatment outcomes, drug toxicity and prognosis in ALL patients; 2) Predictive model derived from pharmacogenetic information will be effective and reasonable approach to stratify ALL patients according to their clinical outcomes; 3) The SNP-based predictive model could be reasonably applied to the treatment of ALL patients, thus becoming a basis for further improvement of treatment outcome; 4) Finally, this project will enhance and facilitate the pharmacogenetic research in the hematology area, thus make the team to lead the pharmacogenetic research in the world.

Acute lymphoblastic leukemia is the most common form of childhood cancer with current treatment survival rates approaching 80%. Improved outcomes show an increased number of survivors at risk for long-term treatment related side effects including osteonecrosis. Osteonecrosis, or bone death, is caused by blood supply loss to the bone causing pain and poor quality of life. The hips, shoulders, knees and ankles may be affected. Pain is the usual presenting symptom and may become severe requiring surgical decompression or replacement of the affected joint. Long-term effects including arthritis and progressive joint difficulties will not be known for decades. This study aims to determine the risk factors for developing osteonecrosis that will lead to information for earlier detection and prevention. The study will be the basis for future intervention and prevention trials.

This study aims to characterize clonal evolution in chronic lymphocytic leukemia (CLL) using different approaches and to identify a possible association with disease progression, i.e. therapy initiation. Samples This monocentric study is carried out using representative bioarchived leukemic samples with a diagnosis of CLL, either at diagnosis or at evolution. These bioarchived samples were collected locally at our center during years of diagnostic activity, and were accurately pathologically, cytogenetically and molecularly characterized. Clinical data The clinical data were retrospectively collected through collaboration with the referring physicians. Methods Samples will be investigated by means of (1) conventional cytogenetics, (2) fluorescence in situ hybridization (FISH) and (3) SNP-arrays. After analysis of the array data sets, significant results will be validated and in addition, results will be correlated with clinical data.

The purpose of the present study is to develop a biological prognostic index in patients with Binet stage A Chronic Lymphocytic Leukemia (CLL) who do not necessitate therapy according to NCI guidelines and to prospectively validate the proposed score system based on the absence/presence of 1, 2 or 3 unfavorable prognostic markers such as cluster of differentiation 38 (CD38) expression, Zap-70 expression and immunoglobulin heavy chain variable region (IgVH) configuration.

Since methotrexate toxicity represents a major problem in patients treating with cancer and there are few studies about the role of vitamin D in the pathogenesis of this toxicity, so the aim of the present study is investigation of the effect of vitamin D administration on methotrexate toxicity such as oral ulcerations, bone marrow toxicity as well as renal and hepatic toxicity also the role of inflammatory mediators and oxidative stress markers in methotrexate toxicity will be evaluated, taking in consideration the dose of leucovorin rescue.

Haematological malignancies constitute the most common neoplastic disease in child population, with acute leukemia occupying the number one spot with a percentage of 32.8%. In children, leukaemia is primarily encountered in its acute form (97%) and in the majority of the cases it is presented as Acute Lymphoblastic Leukaemia - ALL (80%). Acute Non-Lymphoblastic Leukemia - ANLL is encountered less frequently (17%) and it includes Acute Myelogenous Leukaemia - AML (15%) and some other rare forms (2%), while the remainder 3% corresponds to chronic leukaemia. L-Asparaginase (L-ASP) is a fundamental component during the loading phase with regards to achieving remission of the disease and, likewise, during the maintenance phase with the intention of establishing that remission in both children and adults suffering from ALL. The cytotoxic effect of the exogenous administration of Asparaginase is caused by the depletion of the reserve of asparagine in the blood. Asparaginase (ASP) acts as a catalyst for the hydrolysis of asparagine to aspartic acid and ammonia. Asparagine is vital for protein and cell synthesis and, therefore, for their survival. The normal cells of the human body have the ability to produce asparagine from aspartic acid, with the assistance of the enzyme asparagine synthetase. However, the neoplastic cells either lack the enzyme completely or contain minute amounts of it resulting in their inability to synthesize asparagine de novo. The survival of these cells and their ability to synthesize proteins depends entirely on receiving asparagine from the blood. Thus, the administration of ASP leads to the inhibition of DNA, RNA and protein synthesis which, in turn, results in the apoptosis of these cells. Despite L-ASP's paramount importance in the chemotherapy treatment of leukaemia, it is responsible for a plethora of toxic adverse effects that sometimes even require the termination of its administration. A critical adverse event of ASP is a disorder in the metabolism of lipids. Specifically, it appears that the activation of the endogenous pathway that produces triglycerides through hepatic synthesis leads to hypertriglyceridaemia. The liver is capable of synthesizing VLDL (Very Low Density Lipoproteins) that are rich in triglycerides. Utilising the effect of the enzyme Lipoprotein Lipase (LpL), located on the vascular endothelium, the triglycerides detach from the VLDL causing the latter to transform into IDL (Intermediate Density Lipoproteins) and afterwards into LDL (Low Density Lipoproteins). The triglycerides are later extracted from the blood circulatory system and stored in the adipose tissue, while the LDL particles connect with tissue receptors or macrophage receptors. The final products of the breakdown (coming from the peripheral hydrolysis of triglycerides with the help of LpL) of chylomicrons, VLDL, the remnants of lipoproteins, will eventually be removed by hepatic receptors. Apolipoprotein E (Apo-E) plays an important role in this procedure, it binds these remnants in the presence of LpL and hepatic lipase. Along the duration of the treatment with ASP, reduced LpL functionality is recorded, resulting in impaired plasma clearance of triglycerides and an increase in their levels, while L-ASP appears to cause disorders in other lipid factors, such as cholesterol, HDL and apolipoprotein A. Disorders of lipid metabolism have been found to be associated with polymorphisms of the LpL and Apo-E genes, sometimes with positive and sometimes with negative effects on the lipid profile and more likely participation in cardiovascular complications. The current study will evaluate, the lipid profile of children with ALL, the effect of L-ASP on the lipid profile of the aforementioned patients, as well as the correlation between the polymorphisms of Lipoprotein Lipase (LpL) and Apolipoprotein E (ApoE) with the values of the lipids during chemotherapy. Both the universal and national bibliography that pertain to the effect of ASP on the potency of LpL and App E and to the values of the lipids in children that suffer from ALL during chemotherapy with L-ASP is limited, while there exists no bibliographic reference correlating the genetic background to LpL and Apo E and the relation of the lipid profile. The current study will examine for the first time gene polymorphisms of LpL and Apo E in children with ALL during treatment with ASP.

NVP-BEP800, a new HSP90 inhibitor, has particularly interesting therapeutic potential and represents hope in cancer pathologies. While it is currently being tested for solid cancers, no preclinical study has yet demonstrated its effectiveness in acute lymphoblastique leukemia (ALL). The investigators wish to study the effects of NVP-BEP800 on two different types of ALL (T and B-ALL).

Sarcopenic obesity occurs when there is a loss of muscle and gain of fat in the body. With this study, the investigators will explore how nutritional status at the beginning of the treatment can cause changes in your child's body fat compared to muscle in the body. The investigators will also look at how these changes can impact a child's cancer treatment, survival from treatment, and if there is any deterioration in health and nutrition status. The primary objective of this study is to establish the incidence of sarcopenic obesity, measured by dual-energy x-ray absorptiometry (DEXA), among Indian children and adolescents with acute lymphoblastic leukemia (ALL).