View clinical trials related to Leukemia, Lymphoid.
Filter by:This research study is evaluating a drug called ribociclib (LEE011) given in combination with everolimus and other standard of care chemotherapy drugs as a possible treatment for relapsed or refractory ALL. The names of the drugs involved in this study are: - ribociclib - everolimus - dexamethasone
This phase III trial compares adding a new anti-cancer drug (venetoclax) to the usual treatment (ibrutinib plus obinutuzumab) in older patients with chronic lymphocytic leukemia who have not received previous treatment. The addition of venetoclax to the usual treatment might prevent chronic lymphocytic leukemia from returning. This trial also will investigate whether patients who receive ibrutinib plus obinutuzumab plus venetoclax and have no detectable chronic lymphocytic leukemia after 1 year of treatment, can stop taking ibrutinib. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with obinutuzumab may induce changes in body's immune system and may interfere with the ability of cancer cells to grow and spread. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving ibrutinib and obinutuzumab with venetoclax may work better at treating chronic lymphocytic leukemia compared to ibrutinib and obinutuzumab.
Ibrutinib, a first-in-class Bruton Tyrosine kinase (BTK) inhibitor, has become an established treatment in relapsed/refractory chronic lymphocytic leukemia (CLL). However, despite a considerable improvement of Progression Free Survival (PFS) and Overall Survival (OS) in comparison with historical controls, the prognosis of patients with 17p deletion (del17p) remains a concern, as it is clearly much less favourable than that of patient without del17p. Again, TP53 mutations correlated to poorer prognostic in Relapsed/Refractory (R/R) CLL patients treated with ibrutinib (Brown JR et al,2018). Despite these therapeutic advances, the treatment of CLL with TP53 disruption thus remains a difficult issue that warrants evaluation of alternative treatment strategies, in particular the use of ibrutinib in combination with other agents. A body of evidence suggests that targeting the extracellular molecule CD38 might be an interesting option. CD38 is a transmembrane glycoprotein with multiple receptor and enzymatic functions. The interaction of CD38 with its ligand CD31 (also known as Platelet Endothelial Cell Adhesion Molecule (PECAM-1)) not only plays a role in the binding and the migration of leucocytes through the endothelial cells wall but also triggers the activation of intracellular pathways involved in the differentiation and activation of B cells. Previous results strongly suggest that CD38 favours the expansion of CLL clones not only directly by transducing a proliferation signal but also by directing them to anatomic sites where they find favourable conditions for proliferation and survival. Daratumumab is a first-in-class human IgG1ĸ monoclonal antibody (mAb) that binds CD38-expressing malignant cells with high affinity. Daratumumab induces tumor cell death through multiple mechanisms such as antibody-dependent cell-mediated cytotoxicity (ADCC), complement dependent cytotoxicity (CDC), antibody-dependent cellular phagocytosis (ADCP) and induction of apoptosis (de Weers et al, 2011). Recent data show that daratumumab may also display an immunomodulatory effect through depletion of a subset of immunosuppressive CD38+ Tregs (Krejcik et al, 2016). Early-stage clinical trials found daratumumab to be safe and to display encouraging clinical activity as a single agent in relapsed/refractory multiple myeloma (MM) patients (Lockhorst et al 2016, Lonial et al, 2016). Overall response rate was 31%, with rapid (median 1 month) and durable responses in this heavily pretreated MM population. Interestingly, no patient discontinued the treatment because of drug-related adverse events. These results led to approval of daratumumab in relapsed/refractory MM in December 2015. The clinical efficacy of daratumumab along with its very favourable safety profile supports its investigation in other lymphoproliferative malignancies. In particular, the expression of CD38 in poor prognosis CLL and the key role of CD38 in CLL biology provide a basis for examining the potential of daratumumab in this disease. In preclinical studies, (Matas-Céspedes et al, 2016; Manna et al, 2017) Daratumumab efficiently kills CLL cell lines and patient-derived CLL cells by ADCC and ADCP in vitro. Daratumumab modulates CLL-T reg levels and increase cytotoxic effector T cells. Rationale for combining ibrutinib with daratumumab: These data suggest that combining ibrutinib with daratumumab might have a synergistic or additive effect. Both drugs inhibit B cell receptor (BCR) signalling via two different converging pathways, i.e. BTK and CD38/ZAP70/ERK (Deaglio et al, 2007). In vitro, Manna et al have shown that daratumumab is able to modulate BCR signaling. Interestingly, the ibrutinib /daratumumab combination significantly enhanced mitochondrial-mediated apoptosis bth in CD38 high and CD38 low CLL cells (Manna et al, 2017). Altogether, this provides a rationale for evaluating the safety and efficacy of the association of daratumumab with ibrutinib in high-risk relapsed/refractory patients for whom the standard-of-care using ibrutinib as a single agent has demonstrated limitations in terms of long-term disease control. Primary objective of the study: to determine the efficacy of a treatment combining daratumumab and ibrutinib in a poor risk population of relapsed CLL patients with TP53 dysfunction. Secondary objectives of the study : to determine the safety profile of daratumumab in combination with ibrutinib in CLL patients. Inclusion period: 24 months Treatment duration (ibrutinib + daratumumab): continuous, until disease progression or unacceptable toxicity. Follow-up period: will begin once the subject discontinues study treatment, during 2 years.
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.
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.
This phase III trial studies how well ibrutinib and obinutuzumab with or without venetoclax work in treating patients with chronic lymphocytic leukemia. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Obinutuzumab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving ibrutinib, obinutuzumab, and venetoclax may work better than giving ibrutinib and obinutuzumab in treating patients with chronic lymphocytic leukemia.
This is a single center, open-label, phase 1 study to determine the safety and feasibility of infusing CART22-65s with or without huCART19 after administration of lymphodepleting chemotherapy in adult patients with relapsed or refractory B-ALL.
The purpose of this study is to determine the efficacy of bendamustine and rituximab (BR) followed by venetoclax for 12 months. The total time on therapy is 15 months. Bendamustine and rituximab is a commonly used treatment for CLL. Venetoclax is an oral drug that blocks a protein called BCL-2 which is present on CLL cells. It is approved for patients with relapsed (the cancer has come back) or refractory (the cancer did not respond) CLL who harbor a deletion in the short arm of chromosome 17 [del(17p)]. When this drug is used by itself, many patients needed to be admitted to the hospital to monitor for a complication known as tumor lysis syndrome. This is an oncologic emergency that is caused by massive destruction of tumor cells with the release of large amounts of electrolytes and other molecules into the blood that can lead to renal failure and potentially death.
In this study, adults with newly-diagnosed Philadelphia Chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) will receive first-line therapy of ponatinib or imatinib. The main aim of this study is to compare the number of participants on each treatment that show no signs of disease. Participants will take tablets of either ponatinib or imatinib at the same time each day combined with reduced-intensity chemotherapy for up to 20 months. Then, they will continue with single-agent therapy (ponatinib or imatinib) until they meet the discontinuation criteria from the study.
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