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).
This is a single arm, open-label, multi-center, phase I/II study to determine the engraftment, safety and clinical activity of allogeneic CARCIK-CD19 cells in adult and pediatric patients with relapsed/refractory mature B-cell neoplasia expected to express CD19 i.e. B-cell NHL and CLL. CARCIK-CD19 will be produced from the peripheral blood of an at least haploidentical familial donor.
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.
A randomized, multi-centre trial was conducted between 2013-2016, including 128 patients with untreated CLL from eight hematological clinics in Sweden. Vaccination with polysaccharide pneumococcal vaccine (PPSV23) or conjugated pneumococcal vaccine (PCV13) was performed and the results were published 2018. PCV13 showed a superior immune response, measured as OPA (opsonophagocytic assays) and ELISA (enzyme-linked immunosorbent assay), compared to PPSV23. Immune cells analyses after primary immunization will be performed. Between 2019-2021 a prospective follow up study was conducted of the same cohort and also included a control group. The study participants have been revaccinated with pneumococcal vaccines with the aim to evaluate the effect of repeated dose of PCV13. The antibody response (measured as titer with FMIA (fluorescent multiplexed bead-based immunoassay) and antibody function with MOPA (multiplexed opsonophagocytic assay) will be performed. Studies investigating the dynamics of immune cells before and after primary immunization and revaccination will be performed. The study will give important answers about the optimal vaccination strategy in patients with CLL and can improve the vaccination recommendations in immunocompromised patients.
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.
A Phase 2 study of Zandelisib with Venetoclax (VEN) and Rituximab (R) in subjects with Relapsed/Refractory CLL.
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.
The primary objective of this study is to determine the recommended phase 2 dose (RP2D) and characterize the safety profile of TG-1801. As per protocol v3.0, ublituximab will be discontinued.