Active clinical trials for "Leukemia, Lymphoid"

Venetoclax and ibrutinib have complementary activity in clearing the disease across anatomical compartments. By combining ibrutinib with venetoclax, cells can be mobilized from tissues into the bloodstream by ibrutinib and killed in the blood by venetoclax. Consistently, the venetoclax-ibrutinib combination can achieve undetectable minimal residual disease (MRD-neg) in a sizable proportion of patients. Gentle debulking obtained with a lead-in phase of ibrutinib monotherapy may allow starting venetoclax when the disease has been reshaped in a size that fits for low-risk of tumor lysis syndrome (TLS), a rare adverse event (AE) of venetoclax. MRD-guided treatment duration may allow patients achieving a negative status to gain drug-free intervals and less medicalization, and may avoid all the potential, and not yet completely known implications of continuous therapy on long-term safety, drug interactions, quality of life, compliance to treatment, and economic sustainability.

The GRAALL-QUEST study is a Phase 2 study nested in the GRAALL-2014/B study (NCT02617004). The GRAALL-QUEST study evaluates the safety and the efficacy of blinatumomab-containing consolidation and maintenance therapy in patients aged 18-59 years old with high-risk B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in first complete hematologic remission after one induction course of standard chemotherapy and no central nervous system (CNS) involvement at diagnosis. High-risk patients are defined as patients with KMT2A/MLL gene rearrangement, and/or IKZF1 (Ikaros) intra-genic deletion and/or high post-induction Ig-TCR minimal residual disease (MRD) level (≥10-4). In such patients not receiving blinatumomab, 3-year hematologic relapse incidence and relapse-free survival (RFS) are estimated at 60-65% and 50% only, respectively, on the basis of historical results. A large subset of these high-risk patients (i.e. those with post-induction MRD level ≥10-3 and/or post-consolidation MRD level ≥10-4), but not all, will also be considered as candidates for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first hematologic remission. The primary objective of the GRAALL-QUEST study is to evaluate the efficacy of adding blinatumomab to consolidation and eventually maintenance therapy in term of Relapse Free Survival (RFS). Secondary objectives are overall survival, comparison of RFS and Overall Survival (OS) in transplanted versus non-transplanted patients, MRD response and safety. Blinatumomab will be given as monthly cycles at the daily dose of 28 microg/d continuous IV infusion, together with 3 triple intra-thecal (IT) chemotherapy injections. The first cycle will start after completion of the first consolidation chemotherapy phase (corresponding to the MRD2 time-point). Patients receiving allo-HSCT will receive successive blinatumomab cycles until allo-HSCT. Patients not receiving allo-HSCT will receive a first blinatumomab cycle (cycle 1) during the second consolidation chemotherapy phase, followed by late intensification, then the third consolidation chemotherapy phase including another blinatumomab cycle (cycle 2) and maintenance chemotherapy including three additional blinatumomab cycles (cycles 3 to 5), for a total of 5 blinatumomab cycles maximum.

Non-Hodgkin CD20 + Indolent Lymphoma (iNHL) and Chronic Lymphatic Leukemia (CLL) are the most frequent neoplasms of B lymphocytes. They include various histologies (follicular NHL, marginal zone NHL and Lymphocytic NHL/ CLL) characterized by a chronic course and prolonged survival, but while patients with a limited disease could be cured, those with advanced disease or relapsed after localized radiation therapy are generally considered untreatable through standard treatments. The options for first-line therapy include the use of the FCR scheme, based on Fludarabine, Cyclophosphamide and Rituximab or the BR, with Bendamustine and Rituximab. Despite good results, treatment with these two regimens (FCR or BR) is associated with severe immunosuppression which worsens the immunological dysfunction already present at diagnosis in several patients. It has been shown previously that the adoptive transfer of ex vivo anti-CD3/CD28 co-stimulated autologous T cells can successfully accelerate a robust early recovery of T cells after autologous transplantation in multiple myeloma. These CD3/CD28 expanded T cells cannot however be used in NHLi and CLL due to the presence of contaminating tumor cells in the preparation. Polyclonal T cells can also be expanded in vitro in presence of Blinatumomab and recombinant human IL2 (rhIL2) and have been called BET (Blinatumomab-expanded T cells). They are a product of Advanced Therapeutic Medicinal Product (ATMP) composed of polyclonal CD8 and CD4 T cells that are still functional and devoid of contaminating CD19+ neoplastic cells. Based on these data, it was hypothesized that infusion of BET in patients with iNHL/CLL, after the first treatment line (with FCR or BR), could induce adequate immunological recovery.

This phase I/II trial studies the best dose of venetoclax when given together with ponatinib and dexamethasone and to see how well they work in treating participants with Philadelphia chromosome or BCR-ABL positive acute lymphoblastic leukemia or chronic myelogenous leukemia that has come back or does not respond to treatment. Drugs used in chemotherapy, such as venetoclax and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Ponatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving venetoclax, ponatinib, and dexamethasone may work better in treating participants with acute lymphoblastic leukemia or chronic myelogenous leukemia.

This research study is evaluating the combination of three drugs - acalabrutinib, venetoclax, and obinutuzumab -- as a possible treatment for chronic lymphocytic leukemia (CLL). The drugs involved in this study are: Acalabrutinib Venetoclax Obinutuzmab

Evaluate the safety (P-I), pharmacokinetics and anti-tumor effect of immunotherapy of autologous T cells genetically modified to express anti-CD19 chimeric antigen receptor (CAR) (TBI-1501) for relapsed or refractory CD19+ B-cell acute lymphoblastic leukemia.

The purpose of this study is to evaluate the safety, pharmacokinetics, immunogenicity, and efficacy of zilovertamab vedotin given intravenously (IV) across a range of dose levels in participants with previously treated hematological cancers including acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), Burkitt lymphoma (BL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), Richter transformation lymphoma (RTL), and T-cell non-Hodgkin lymphoma (NHL).

This is an open-label, two-part study to assess the safety, tolerability, pharmacokinetics and clinical efficacy of acalabrutinib in Chinese adult subjects with R/R MCL, CLL and other B-cell malignancies. The study is divided into 2 parts: Phase 1 portion and Phase 2 portion.

Based on the promising results obtained with ibrutinib as single agent, the results obtained with ibrutinib in combination with ofatumumab in a previous phase I/IIb study (Jaglowski 2015), and since data from in vitro studies do not support a synergistic effect of the combination of ibrutinib and anti-CD20 mAbs, we propose a chemotherapy-free combined strategy based on ibrutinib monotherapy as front line treatment for patients with CLL, with the addition of a consolidation phase with ofatumumab in patients not attaining CR under ibrutinib in order to improve the quality of their response. Since median time to CR with ibrutinib was nearly 12 months, patients will be evaluated at this time point, and those patients not in CR will add consolidated treatment with Ofatumumab. Thus, this multi-center, non-randomized phase 2 study is designed to evaluate the efficacy and safety of ibrutinib alone or in combination with Ofatumumab in patients no attaining CR under ibrutinib as front-line therapy for patients with chronic lymphocytic leukemia.

This phase I trial studies the side effects and best dose of pevonedistat when given together with ibrutinib in participants with chronic lymphocytic leukemia or non-Hodgkin lymphoma that has come back or has stopped responding to other treatments. Pevonedistat and ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.