View clinical trials related to Leukemia.
Filter by:The purpose of this study is to evaluate the safety and efficiency of allogeneic cluster of differentiation 19 (CD19)-directed chimeric antigen receptor modified T cells (CART-19) infusions in patients with relapsed / refractory B-cell acute lymphoblastic leukemia (B-ALL)
This study seeks to examine treatment therapy that will reduced regimen-related toxicity and relapse while promoting rapid immune reconstitution with limited serious graft-versus-host-disease (GVHD) and also improve disease-free survival and quality of life. The investigators propose to evaluate the safety and efficacy of selective naive T-cell depleted (by TCRɑβ and CD45RA depletion, respectively) haploidentical hematopoietic cell transplant (HCT) following reduced intensity conditioning regimen that avoids radiation in patients with hematologic malignancies that have relapsed or are refractory following prior allogeneic transplantation. PRIMARY OBJECTIVE: - To estimate engraftment by day +30 post-transplant in patients who receive TCRɑβ-depleted and CD45RA-depleted haploidentical donor progenitor cell transplantation following reduced intensity conditioning regimen without radiation. SECONDARY OBJECTIVES: - Assess the safety and feasibility of the addition of Blinatumomab in the early post-engraftment period in patients with CD19+ malignancy. - Estimate the incidence of malignant relapse, event-free survival, and overall survival at one-year post-transplantation. - Estimate incidence and severity of acute and chronic (GVHD). - Estimate the rate of transplant related mortality (TRM) in the first 100 days after transplantation.
Patients will be randomized in phase II trials to continue on the same TKI versus one of the alternative treatment approaches. If a patient is not eligible for one of the treatments, he (she) will be randomized between the options for which he (she) is eligible. The trial will start with current available treatment options (experimental arms). New available treatment options may be open at any times later on. Authorized TKIs are imatinib, nilotinib, dasatinib, bosutinib and ponatinib. For all options the treatment duration is for a minimum of 12 months and will be continued in the absence of adverse events following investigator decision. Each therapeutic option will be detailed in term of combination modalities, dose, dose adaptation, specific warnings, specific exclusion and inclusion criteria. The decision to introduce a new option will depend on the general pace of recruitment and on the assessment of the potential efficacy and safety of the new treatment, and will be implemented after scientific review by a protocol amendment. Primary objective: A. To select molecules in combination or sequentially with imatinib, nilotinib, dasatinib, bosutinib or ponatinib potentially able to produce a 25% increase in the Cumulative Incidence of MR4.5 as compare to control. Secondary objectives: A. To determine the safety of selected therapies B. To determine the rate of MR4 by 12, 24, 36, 48 months in experimental and control arms C. To determine the rates of MR4.5 by 24, 36, 48 months in experimental and control arms D. To determine the rate of undetectable BCR-ABL1 transcript (sensitivity 40000 ABL copies) by 12, 24, 36, 48 months in experimental and control arms E. To estimate treatment free remission (TFR) in patients eligible for discontinuation studies F. To investigate the relationship between biological activity and the clinical efficacy of the selected therapies G. To assess the effects of the treatments on the number and clonogenicity of CML stem cells and other biological markers of interest H. To estimate duration of response, progression-free survival, event free survival and overall survival.
Patients with refractory and relapse lymphoblastic leukemia had poor outcome even with marrow ablative conditioning mostly standard iv-Bu-Cy or Cy-TBI. In this study, we focus on a new treatment strategy with high-dose chemotherapy regimen consisting of fludaraibine+cytarabine+cyclophosphamide+etoposide followed by reduced intensity condiotning regimen consisting of fludarabine, busulfan and post-infusion cyclophophamide.
The mandate of this MPN registry is to collect clinical information, including molecular results, from consenting patients with a variety of MPNs at different time points during the course of their disease.
This is a prospective observational cohort study of haploidentical transplantation with post-transplant cyclophosphamide for acute leukemias using reduced intensity conditioning for acute myeloid leukemia (AML) and myeloablative conditioning for acute lymphoblastic leukemia (ALL).
Aldehyde dehydrogenases (ALDHs) are cellular enzymes responsible for detoxifying aldehyde resulting from the metabolism of endogenous and exogenous xenobiotic cellular constituents. Although ALDHs are considered to play an important role in tumorigenesis, the role of ALDH activity in cancer stem cells, and more particularly that of the acute leukemia must be specified. Several studies have shown that ALDHs are potent apoptogenic compounds on normal or cancer cells. Therefore, the cells that were damaged and their increased ALDH activity does not die by apoptosis but become highly proliferating. This result is a plausible mechanism for the "evasion of apoptosis", a characteristic shared by many cancer cells. On this basis, it is proposed an innovative approach to cancer chemotherapy through inhibition of one of the protective mechanisms against apoptosis, ie the increase in ALDH activity than cancer cells put involved in overcoming the lethal effects of damaged roads. ALDHs of inhibitors they may have immediate application as anti -cancer in vivo? The limited experimental data obtained so far on human tumor xenografts in immunodeficient mice and the absence of data on the in vivo toxicology do not allow direct passage to clinical trials. Indeed, some members of the ALDH superfamily are expressed constitutively in some vital organs they protect against the deleterious effects of xenobiotics and adverse endogenous metabolites. Consequently, if ALDHs should be inhibited, of the collateral damages for the normal cells could occur. However, when normal cells have not undergone deleterious exposure, these harmful metabolites are not or in very small quantities, which do not require high levels of ALDH activity, and therefore without harm to the inhibition of cell of these enzymes. From a hematological point of view, it seems essential to test the therapeutic index of the inhibitor of ALDH DIMATE between normal hematopoietic cells and leukemic stem. Indeed, in the pathophysiology of acute leukemia, the leukemia stem cells are of major importance because they are much more resistant to chemotherapy than more differentiated cells and thus causing the high rate of relapse observed in acute leukemia despite the high rate of complete remission often obtained. In this study, it will be tested in vitro sensitivity of the cluster of differentiation 4 and cluster of differentiation 38 (CD4/CD38) highly purified of leukemic origin or normal to the DIMATE compound. The objective will be to analyze the effects of DIMATE on the parameters of the proliferation, the apoptose, the cytokinins of secretions and the changes transcriptomic in general, in order to better define the therapeutic index of this compound and to determine all the precursory hematopoietic normals and leukaemic cellular effects. The reversible cytostatic of DIMATE effect on normal cells but its irreversible apoptotic effect on cancer cells is an advantage to try to eliminate.
This study aims at exploring the activity of a frontline approach based on dasatinib plus steroids administration as induction treatment, followed by the infusion of Blinatumomab, in adult Ph+ ALL.
The purpose of this study is to evaluate the safety and effectiveness of CAR-pNK cell immunotherapy in patients with CD7 positive relapsed or refractory Leukemia and Lymphoma.
The investigators propose to use Belinostat in combination with AZT as consolidation therapy for the treatment of ATLL.