Active clinical trials for "Leukemia, Lymphocytic, Chronic, B-Cell"

The investigators hypothesize that Lipoprotein Lipase (LPL) expression on Chronic Lymphocytic Leukemia (CLL) cells will predict a more aggressive clinical course. The results from this proposal will validate the use of a novel antibody developed at Dartmouth-Hitchcock in CLL and will predict CLL patients that have a more aggressive form of the disease. The investigators work will also provide direct evidence that LPL is expressed on CLL cells and provides a critical source of fatty acids required by the CLL cells to grow and survive. Fatty acid metabolism may become a therapeutic target in CLL in the future.

Efficacy of BCR Inhibitors in the Treatment of Autoimmune Cytopenias Associated with Chronic Lymphocytic Leukemia (CLL): A Retrospective Analysis of the French Innovative Leukemia Organization (FILO)

Ibrutinib (a tyrosine kinase inhibitor targeting Bruton) is a standard of treatment in haematology. According to retrospective data, atrial fibrillation and systemic hypertension are common ibrutinib-related advserse events. The investigators aim at prospectively establishing the incidence of thesedrug related advsere events through clinical monitoring and attempt at identifying populations at risk.

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.

IB-RU-SCOPE is a "routine-clinical practice" oriented cohort observational study of ibrutinib efficacy and safety in approx. 70 patients with chronic lymphocytic leukemia in the Russian Federation

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.

This is a non interventional study to evaluate the efficacy and safety of Chlorambucil plus Rituximab as firstline therapy in elderly and/or unfit patients affected by B-cell Chronic Lymphocytic Leukemia (B-CLL).

Chronic lymphocytic leukemia is the most common type of chronic leukemia, accounting for approximately 40% of all leukemias and mainly affecting older individuals. As it has a highly variable clinical course, identification of molecular and biological prognostic markers has provided new insights into the risk stratification of patients with chronic lymphocytic leukemia.

CLL is an incurable disease with conventional chemotherapy. In the absence of TP53 disruption, a chemoimmunotherapy (CIT) regimen is recommended as front-line and second-line treatment in those patients who attained a long progression-free survival (PFS) with the previous regimen. Bendamustine and rituximab (BR) is one of the most widely adopted CIT regimens, including second-line treatment. Unfortunately, durations of remission following BR combination therapy tend to be short in patients with heavily pre-treated disease or who have already received rituximab. The incorporation of a maintenance following induction chemotherapy to overcome the shorter remission durations in this population is a reasonable option.

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.