View clinical trials related to CLL.
Filter by:The main objective of this study is to compare the efficacy of sonrotoclax plus zanubrutinib versus venetoclax plus obinutuzumab in participants with chronic lymphocytic leukemia (CLL)
The purpose of this study is to assess the safety and tolerability and to confirm the dose of nemtabrutinib in combination with venetoclax in participants with R/R CLL/SLL. The primary study hypotheses are that the combination of nemtabrutinib plus venetoclax is superior to VR with respect to progression-free survival (PFS) per 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria as assessed by blinded independent central review (BICR).
Chronic lymphoid leukemia (CLL) is the most common adult leukemia that is characterized by a malignant monoclonal accumulation of tumoral and quiescent B cells in the peripheral blood. In advanced stages of the disease (Binet stage C), this population invades the bone marrow (BM) and proliferate into the lymphoid organs that results in widespread adenopathy. Richter's transformation is a most aggressive serious complication of CLL (transformation of the disease into an aggressive lymphoma) detected based on TEP/CT (Positron Emission Tomography/ computerized tomography) that shows highly derived glucose consumption by cancer cells. Clinical data from CLL patients with disease acutisation showed hypermetabolic lymphadenopathy with high standardized uptake value (SUV) whereas there is low grade tracer uptake into BM. We supposed that the tumor microenvironment of the lymphatic niche promotes the proliferation and glycolytic activity of CLL cells which become particularly resistant to treatment. The development of an ex-vivo tumor model that reproduces the microenvironment of the lymph node niche appears essential to identify and validate new therapeutic targets because despite the therapeutic arsenal available some patients still relapse or are refractory to treatment. Our objectives are to i / Characterize this niche of resistance by the development of an ex-vivo tumor model and ii / Evaluate in-vitro the effectiveness of the association of current treatments (RFC, Ibrutinib or Venetoclax) with anti-metabolic therapies (inhibitors of glycolysis) Our lab is developing an ex-vivo models of the lymphatic niche in CLL based on co-cultures of leukemic cells from patients stimulated with CpG ODN and IL2 with primary human lymphatic fibroblasts (HLF) (EC 12PP15). This co-culture has never been described in the literature and allows us to study the lymphatic niche of CLL patients. Lymph node (LN) exploration in CLL requires invasive access and does not bring any additional information in initial diagnosis. Then, we validated our co-culture model using complementary approaches: increased viability, proliferation, and resistance to Ibrutinib, associated with increased production of anti-apoptotic proteins such as MCL1 and BCL2 after 48 hours of co-culture. Secondly, we studied the metabolism in this resistance niche. We find an increased production of lactate and an acute consumption of glucose, associated with a strong metabolic activation detected by SEAHORSE and by the production of glycolysis enzymes such as hexokinase 2. Our study constitutes an original project because it characterized the energy metabolism of the CLL lymphatic niche by developing an original ex-vivo model and enhanced our understanding of the contribution of the specific microenvironment in the dissociation of metabolic activity using SUV max in BM and lymphatic niche. Anti-metabolic therapies are efficient on co-culture CLL cells and could be an alternative for refractory or relapsed patients under current treatment.
The goal of CICERO is to investigate the clinical outcome with a particular focus on prospective data on safety using acalabrutinib (+/- obinutuzumab) in CLL patients receiving co-medication with DOACs (edoxaban, rivaroxaban, dabigatran, apixaban) irrespective of treatment line.
The purpose of this study is to collect medical informations and samples from refractory and/or relapsed chronic lymphocytic leukemia during or after venetoclax treatment, in order to evaluate the frequency of resistance mechanisms.
This is a Phase 1/2 study of GB261 in participants with relapsed or refractory B-cell NHL and CLL. The study will consist of a dose-escalation stage(Phase 1), an expansion stage(Phase 2a) and Phase 2b stage where participants will be enrolled into indication-specific cohorts.
In this biological study, blood samples will be collected from patients with CLL treated with targeted agents (ibrutinib and venetoclax) to assess the impact of these treatments on the generation of CAR T cells in terms of manufacturing efficiency, immunophenotypic characteristics and functional properties.
Many patients with CLL have a weakened immune system due to their disease. It increases their risk of developing serious, treatment-requiring infections such as blood poisoning or pneumonia, which in the worst case may end with fatal outcomes. Serious infections due to CLL are responsible for one third of all deaths among CLL patients. PreVent-ACaLL study will investigate whether a combination of two known types of cancer drugs can reduce the risk of infection and thus mortality when given preventively to newly diagnosed CLL patients. A newly developed register-based computer model can predict which patients are at high risk in order to develop infections as a result of their CLL. A preventive treatment might be initiated before patients need chemotherapy. In this way, the cancer disease might be "reset" so that the immune system, which is inhibited by CLL, is restored and the risk of fatal infections is minimized.
Long term follow-up of patients with chronic lymphocytic leukemia (CLL), B-prolymphocytic leukemia (B-PLL), T-cell prolymphocytic leukemia (T-PLL), Small lymphocytic lymphoma (SLL), T/Natural Killer large granular lymphocyte leukemia (T or NK-LGL), Hairy cell leukemia (HCL) and Richter's transformation
Recently, a novel assay for detecting heavy/light chain (HLC) ratios has been reported which enables improvement in paraprotein detection and monitoring in multiple myeloma and other plasma-cell dyscrasias. The prognostic and biological role of the HLC assay has as yet not been studied in CLL. Aims of the proposed study: 1. To quantify and analyze the prognostic significance of HLC ratios in the serum of CLL patients. (In addition to FLC) 2. To study the different patterns of Immunoglobulin's subclass antibodies in the serum of patients with CLL and compare them to those of to healthy volunteers. 3. To perform a sub-analysis in patients with CLL who have autoimmune phenomenon (AIHA and ITP)