Active clinical trials for "Leukemia"

Previous findings have shown that a biomarker comprised of the three microRNAs (miRs) miR-451, miR-151-5p and miR-1290 can independently predict precursor B-cell acute lymphoblastic leukemia (B- ALL) patients' risk for relapse when measured in cells from a bone marrow (BM) aspiration taken at diagnosis (Avigad et al., 2016: Genes, Chromosomes & Cancer 55:328-339). Curewize Health recognizes that the development of a minimally invasive blood test for frequent long-term monitoring can greatly benefit pediatric precursor B-ALL patients. Therefore, the current study will investigate the monitoring ability of miR-451, miR-151-5p and miR-1290 measured in blood samples. The study will be performed in two stages: Stage 1-Cross-Sectional Study: Blood samples will be collected from relapsed pediatric B-ALL patients and B-ALL patients in remission. Blood will be collected from each patient in three tubes, for serum, plasma and whole blood analysis, in order to interpret the best blood source for measuring miR-451, miR-151-5p and miR-1290. The level of the miRs in blood will be compared between relapsed B-ALL patients to B-ALL patients in remission. If the Stage 1 Cross-Sectional study is successful, the investigators will continue the clinical trials to the Stage 2 Prospective Monitoring study. Stage 2-Prospective Monitoring Study: Blood will be collected from patients at diagnosis and at routine clinical follow-up. Patients can be up to five years from diagnosis. The source of blood found to be most optimal for measuring the miR levels is Stage 1 will be collected. The final design of the Stage 2 study will be decided after completion of the Stage 1 study.

This is a prospective and international observational study run by the GIMEMA. All data will be centrally collected and analyzed at the GIMEMA Data Center in Rome (Italy). Patients reported outcomes will be collected using internationally validated questionnaires.

Primary objective : To identify epigenetic dysregulations of in vivo TKI-resisting CML cells Hypothesis : An epigenetic dysregulation is involved in the in vivo survival of a CML cell subclone despite the use of TKIs

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm companies with the BCR-ABL fusion gene encoded by the Philadelphia (Ph) chromosome. The BCR-ABL fusion protein(the formation of the chimeric gene BCR/ABL on chromosome 22 and a reciprocal ABL/BCR on chromosome 9,it has no expanded name) plays key role on CML leukemogenesis by activating its downstream signaling pathway of survival and proliferation. Imatinib, a targeted competitive inhibitor of a BCR-ABL tyrosine kinase, changed the clinical treatment and prognosis of CML. As its optimized generation, other tyrosine kinase inhibitors (TKIs), dasatinib and nilotinib have more potent anti-leukemic activity and less side-effect. However, acquired resistance to TKIs is one of the main obstacles to effective CML treatment and is involved in gene amplication of ABL tyrosine kinase point mutations. The outcomes of patients with these ABL tyrosine kinase point mutations have linked to worse prognosis and higher mortality generally. Metabolic adaptations are common in cancer cells, and cancer cells become more dependent on mitochondrial biogenesis. Tigecycline, as a broad-spectrum antibiotics, inhibits mitochondrial biogenesis as its an interesting "side-effect".In recent study,researchers indicated that tigecycline can eradicate cancer stem cells by targeting mitochondrial.Here, the investigators test tigecycline's anti-leukemic activity to chronic myeloid leukemia in vitro.

In recent years, considerable progress has been made in understanding the biology of chronic lymphocytic leukemia (CLL), resulting in the emergence of new therapeutic agents that have significantly improved the long-term survival of patients. However, LLC is still considered an incurable disease. Cytogenetic abnormalities are frequently found in this pathology. Some abnormalities are associated with a more aggressive disease and a poor prognosis. The deletion of chromosome 17p (del (17p)), in particular, makes leukemic cells more resistant to standard therapy. Chromosome 17p contains the Tumor Protein 53 gene (TP53) which encodes the tumor suppressor protein 53 (P53) protein. P53 plays a central role in the regulation of important cellular functions such as DNA damage response, cell cycle regulation, apoptosis, and drug sensitivity of chemotherapies. In patients with CLL, the loss of p53 function is a major factor of chemoresistance and is associated with an adverse prognosis. The deletion (17p) is observed in approximately 5 to 10% of patients with CLL. In contrast, mutations in the TP53 gene are observed in approximately 30% of patients with CLL. This means that about one-third of patients with CLL have p53 dysfunction. TP53 and / or del (17p) mutated LLC cells show marked mitochondrial dysfunction. This dysfunction is responsible for a deregulation of intracellular redox phenomena, leading to an increase in oxidative stress and an overproduction of reactive oxygen derivatives (ROS). Dimethyl Ampal Thiolester (DIMATE) is an active, competitive and irreversible inhibitor of aldehyde dehydrogenases (ALDH) 1 and 3. In vitro, DIMATE eradicates human cells from acute myeloblastic leukemia (AML). In patients with CLL, current treatments, particularly effective, do not specifically target pathological B cells. This results in chronic B lymphopenia and hypogammaglobulinemias that provide severe long-term infections, which is the leading cause of death in patients with CLL. Through this study, we will study, in vitro, the expression of ALDH 1, 3, 9 but also of glutathione (GSH) and ROS on tumor B lymphocytes and healthy patients carrying an LLC. Depending on the differences in expression observed, DIMATE could specifically eradicate leukemic lymphocyte cells by sparing healthy lymphocytes, a hypothesis that will be tested in vitro. A special evaluation will be made in patients with del (17) and / or TP53 mutation whose prognosis is still considered unfavorable despite new therapeutic advances.

FCR (fludarabine, cyclophosphamide, rituximab) combination is currently accepted as the gold standard in treatment of younger and physically fit CLL patients. These excellent results, however, cannot be generally applied to the whole CLL population. This is because the median age at diagnosis of CLL lies between 65 and 72 years and patients older than 65 years in fact account up to 50%-75 % of the CLL population. Nevertheless, such population is considerably underrepresented in most of the large clinical trials in CLL/SLL. Therefore, it is not clear whether elderly/comorbid patients could profit from newer treatment approaches such as purine analog combinations or chemoimmunotherapy. Several publications demonstrated unacceptable toxicity of full-dose FC/FCR in elderly CLL patients. However, regimens using attenuated doses of fludarabine and cyclophosphamide showed promising efficacy and low toxicity.

Myelodysplastic syndromes (MDS) are frequent diseases in elderly patients (median age: 71 years). IPSS classification defines low risk (Low and Intermediate 1), and high risk (Intermediate 2 and High) MDS. High-risk MDS (MDS-HR) have a high risk of transformation into acute leukemia with multilineage dysplasia (AML-DML). The success of Azacitidine has been mainly achieved through a rigorous empirical and clinical research, but the molecular mechanisms by which this molecule exerts its effects remain poorly characterized. The primary mode of action of Azacytidine is through DNA demethylation, and integration in to mRNA that favor traduction inhibition. The impact of this molecule on various cell death programs involved in the elimination of leukemic cells : apoptosis and autophagy is currently poorly known. The research program and clinical studies we proposed focus on two major aspects: - Main objective: Molecular mechanism of action and resistance to Azacitidine: Role of apoptosis versus autophagy. - Secondary Objective: Reversion of Azacytidine resistance using different drugs targeting apoptosis and/or autophagy. Our laboratory has identified new molecules to selectively induce different types of cell death (apoptosis or autophagy).

Acute leukemias are commonly seen in elderly and have no effective therapy. In recent years, small molecule inhibitors have shown a tremendous promise in cancer treatment such as chronic myeloid leukemia and lung cancer. Thus, in this proposal, we intend to use our novel patented "indole" compound to conjugated with hydroxamic acid in histone deacetylases inhibitor, suberoylanilide hydroxamic acid and further modify its structure to generate novel small-molecule anticancer compounds. By screening acute leukemic cell lines, we will look for compounds that have shown potential for future drug development. In our preliminary studies, we have identified a novel compound, MPT0E001, to have marked growth inhibitory activity, induce apoptosis and downregulate c-Myc protein level. We intend to use MPT0E001 as a basis to develop novel compounds and test them in multiple leukemic cell lines and primary leukemia samples (Specific aim 1) and identify the mechanisms for downregulation of c-Myc and other pathways such as NF-kappaB and Akt (Specific aim 2). Once we have identified the lead compounds, we will use murine model to assess the acute toxicity profiles in different dose ranges and examine the effects of blood counts and vital organs. After toxicity study, we will test the lead compounds using in vivo xenogenic murine model using both cell lines and primary leukemia. Using this approach, we hope to develop novel compounds that are able to be used in future leukemic therapy.

Nowadays approximately 80% of children and adolescents with acute lymphoblastic leukaemia (ALL) or lymphoblastic lymphoma (LBL) can be cured and become long-term survivors. Avascular osteonecroses (ON) appear as serious side-effect of antileukaemic treatment. Frequently ON are first diagnosed at higher and than irreversible stages (ARCO III, IV). At these advanced stages curative treatment options are not available. Hence ON are associated with considerable morbidity concerning pain and immobility and go along with long-term impairment of quality of life. Therefore early diagnosis of ON in the follow-up of children and young adults with ALL or LBL is a pressing object. Within the prospective multicentric observational OPAL-trial patients at risk (aged 10 years or older) treated according to the clinical trials ALL-BFM(Berlin-Frankfurt-Muenster Study Group), COALL or NHL (Non Hodgkin Lymphoma)-BFM in Germany should be examined with regard to the development of ON. By using a treatment associated, risk orientated assessment and examination incidence, symptoms and the clinical course of ON are investigated. The validity of MRI screening in the early diagnosis of ON in children and young adults is analysed. Systematical investigation of patients under antileukaemic treatment is intended to contribute to risk adapted diagnostic strategies and to serve as data base for the subsequent evaluation of preventive and interventional approaches for the treatment of ON. Long-term objective is the reduction of ON-associated morbidity.

RATIONALE: Collecting and storing samples of tumor tissue, blood, bone marrow, and other body fluids from patients to test in the laboratory and collecting information about the patient's health and treatment may help doctors learn more about cancer and help the study of cancer in the future. Studying these samples in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. It may also help doctors predict how patients will respond to treatment. PURPOSE: This research study is collecting and looking at blood and tissue samples in children with newly diagnosed acute lymphoblastic leukemia.