View clinical trials related to Leukemia.
Filter by:The NK cells participate in the innate immunity against infectious agents or transformed cells that are recognized as "no self" by the absent, weak or abnormal expression of human leukocyte antigen (HLA) class I molecules. According to the "missing self hypothesis", a negative signal is delivered to NK cells when their inhibitory receptors are engaged by the specific HLA class I molecules. NK activation requires a positive signal delivered by the engagement of activating receptors, more particularly of the "Natural cytotoxicity receptors" or NCRs who are directly involved in the natural cytotoxicity of Natural Killer. The activating receptors include NKp46, NKp44 and NKp30, also called NCR 1, 2 and 3 respectively. NKp46 and NKp30 are constitutively expressed on the surface of the NK, the expression of NKp44 is observed only after activation of cells NK. NK cells from most (80%) healthy donors express a high quantity of NCR on their surface, corresponding to the NCRbright phenotype while only 20 % present the NCRdull phenotype. In sharp contrast, most patients (80%) having leukaemia have the NCRdull while only 20 % patients have the NCRbright phenotype. The culture of NK from healthy donors ( NCRbright) with leukaemic cells result in decreased expression of the NKp30 while there is no difference on expression if these same NK are cultivated with cells from healthy donors. Moreover, study of AML patients showed that the NCRdull phenotype was acquired during leukemia development because it was observed its complete (for NKp46) or partial (for NKp30) reversibility in patients achieving complete remission (CR). Reversibility of the NCRdull phenotype after CR suggested that leukemia cells might be involved in NCR down-regulation. In line with these observations, we aim to study the mechanism of NCR down-regulation by cultivating NK NCRbright from healthy donors with leukaemic cells or healthy haematopoietic cells, in order to observe the appearance of the NCRdull phenotype and verify by qPCR if this down-regulation is transcriptionnal. If this hypothesis is be verified, we will study the regulation of NCR by focusing on the implication of genes NCR transcription factors via bio-informatic analysis of putative transcription factors fixation sequences in the promoters of these genes, followed by the verification of the capacity of identified sequences to bind transcription factors. Ultimately, we will verify the real implications of these transcription factors by studying the effect of their silencing by RNA interference experiments.
Acute lymphoblastic leukemia (ALL) accounts for 30 % of all childhood malignancies. The patients undergo four phases of treatment, finishing with a late maintenance phase in which 6-mercaptopurine and Methotrexate are essential components. Insufficient treatment intensity in this phase is associated with increased risk of relapse. Excessive variation in the bioavailability of 6-mercaptopurine has been observed which can cause both risks of undertreatment/relapse as well as overtreatment with severe side effects. In the attempt to achieve individualized 6-mercaptopurine dosing different approaches have been pursued. Nonetheless variation in bioavailability remains a problem. Earlier, oral tablets of 50 mg (Purinethol) were the only administration form of 6-mercaptopurine and it was primarily designed for adult patients. Challenges with accurate dosing and getting the children to swallow the tablets have been a widespread problem, forcing the caregivers to divide or crush the tablets as well as having to administer different dosages over 2-3 days. Due to these problems, an oral liquid formulation of 6-mercaptopurine (Xaluprine) has been developed. However this oral liquid has only been tested on healthy adult volunteers, and not on the target group, childhood patients. This project will assess the bioavailability and plasma kinetics of oral liquid and tablet formulation of 6-mercaptopurine in children with acute lymphoblastic leukemia. The investigators hypothesize to observe comparable plasma kinetics, in children with acute lymphoblastic leukemia when treated with 6-mercaptopurine in the form of a tablet and oral liquid formulation, as previously observed in healthy adults.
To provide the IRB approved mechanism for the prospective collection, analysis and reporting of data on patients who are undergoing either an autologous or allogeneic hematopoietic stem cell transplant for a disease in which a research question is not being addressed and for which peer reviewed, published data have demonstrated efficacy for this treatment approach.
Whether Idarubicin can overcomes multidrug resistant 1 induced chemoresistance with higher induction remission rate than daunorubicin in de novo acute myeloid leukemia patients.Whether induction therapy with IA regimen has a higher remission quality with AML patients than that of DA regimen in high MDR1 expression AML patients.
RATIONALE: Placing a tumor antigen chimeric receptor that has been created in the laboratory into patient autologous or donor-derived T cells may make the body build immune response to kill cancer cells. PURPOSE: This clinical trial is to study genetically engineered lymphocyte therapy in treating patients with CD33 positive acute myeloid leukemias that is relapsed (after stem cell transplantation or intensive chemotherapy) or refractory to further chemotherapy.
RATIONALE: Placing a tumor antigen chimeric receptor that has been created in the laboratory into patient autologous or donor-derived T cells may make the body build immune response to kill cancer cells. PURPOSE: This clinical trial is studying genetically engineered lymphocyte therapy in treating patients with B-cell leukemia or lymphoma that is relapsed (after stem cell transplantation or intensive chemotherapy) or refractory to chemotherapy.
Background: - Cord blood is blood that is taken from the umbilical cord and placenta of healthy newborns after childbirth. The cord blood collected from a baby is called a cord blood unit. Cord blood units are stored frozen in public cord blood banks. About 10,000 cord blood transplants have been performed in children and adults for blood cancers and other diseases in the world. These transplants have helped save lives and improve treatments. However, not all available units of cord blood have been collected, stored, and licensed according to specific government requirements. These unlicensed units can still be used in transplant, but they can only be given as part of specific research studies. This study will evaluate the safety of giving these unlicensed units by recording any problems that may occur during and after giving the cord blood. Objectives: - To test the safety and effectiveness of unlicensed cord blood units in people who need stem cell transplants. Eligibility: - Individuals who are scheduled to have a stem cell transplant. Design: - Participants will be screened with a medical history and physical exam. - Participants will receive the cord blood unit as part of their stem cell transplant procedure. The transplant will be performed according to the current standard of care for the procedure. - After the transplant, participants will be monitored for up to 1 year. Any problems or side effects from the transplant will be treated as necessary. All outcomes will be reported to the National Cord Blood Program and to the Center for International Blood and Marrow Transplant.
Rationale The pharmacokinetics of imatinib and nilotinib, two BCR/Abl tyrosine-kinase inhibitors (TKI), is variable among patients suffering from chronic myeloid leukemia (CML). Transmembrane transporters may play a pivotal role in interindividual variability in TKI disposition. Furthermore, minimum plasma concentrations (Cmin) higher than 1 mg/L could be associated with a higher likelihood of molecular and cytogenetic responses. The TIKlet study is aimed at evaluating correlations among the pharmacogenetics, pharmacokinetics and treatment efficacy/tolerability of imatinib and nilotinib in CML patients. 1. PATIENTS AND METHODS 1.1. Patients Patients affected by CML will be enrolled after the informed consent will be signed, according to the following inclusion criteria: - patients of both sexes, - age between 18 and 80 years, - treated with imatinib or nilotinib, - included in follow-up activities at the participating Hematology Divisions, - able to give informed consent, - with a proved compliance with the scheduled treatment. The administration of other drugs will be allowed, being known the dose and duration of treatment, as well as smoking and herbal products. Alterations in organ functions or physicochemical exams, body mass index >28 do not represent exclusion criteria. 1.2. Enrollment and follow-up visits During enrollment visit: - patients will be informed about the study, their signed informed consent form will be collected and an individual alphanumeric code will be assigned. - Patients' data will be recorded within the individual case report form (CRF) and a blood sample will be obtained. At follow-up visits, a blood sample will be collected for therapeutic drug monitoring (TDM) and patients' CRF will be updated. 1.3. Blood samples After centrifugation, the resulting plasma will be collected for TDM. During the enrollment visit, an aliquot of whole blood will be collected for molecular analyses. 1.4 Laboratory analyses TDM will be performed by high-performance liquid chromatography systems, then results will be evaluated by a population pharmacokinetic analysis. Single nucleotide polymorphisms will be investigated in the following genes: ABCB1, ABCG2, hOCT1, OCTN1, OATP1A2. Finally, response to drugs, in terms of Major Molecular Response (MMR) and Complete Cytogenetic Response (CCyR), and tolerability will be evaluated. Any possible correlation among drug disposition, pharmacogenetics and treatment effects will be analyzed.
Subjects on this study have a type of lymph gland cancer called Non-Hodgkin Lymphoma, acute lymphocytic leukemia, or chronic Lymphocytic Leukemia (these diseases will be referred to as "lymphoma" or "leukemia"). The lymphoma or leukemia has come back or has not gone away after treatment. The body has different ways of fighting infection and disease. No one way seems perfect for fighting cancers. This research study combines two different ways of fighting disease, antibodies and T cells, hoping that they will work together. Both antibodies and T cells have been used to treat patients with cancer. They have shown promise, but have not been strong enough to cure most patients. T cells can kill tumor cells but normally there are not enough of them to kill all the tumor cells. Some researchers have taken T cells from a person's blood, grown more of them in the laboratory and then given them back to the person. The antibody used in this study is called anti-CD19. It first came from mice that have developed immunity to human lymphoma. This antibody sticks to lymphoma cells because of a substance on the outside of these cells called CD19. CD19 antibodies have been used to treat people with lymphoma and leukemia. For this study, anti-CD19 has been changed so that instead of floating free in the blood it is now joined to the T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor. In the laboratory, the investigators found that T cells work better if they also add proteins that stimulate T cells, such as one called CD28. Adding the CD28 makes the cells last longer in the body but not long enough for them to be able to kill the lymphoma cells. The investigators believe that if they add an extra stimulating protein, called CD137, the cells will have a better chance of killing the lymphoma cells. The investigators are going to see if this is true by putting the CD19 chimeric receptor with CD28 alone into half of the cells and the CD19 chimeric receptor with CD28 and CD137 into the other half of the cells. These CD19 chimeric receptor T cells with CD28 and with or without CD137 are investigational products not approved by the FDA. The purpose of this study is to find the biggest dose of chimeric T cells that is safe, to see how long the T cell with each sort of chimeric receptor lasts, to learn what the side effects are and to see whether this therapy might help people with lymphoma or leukemia.
This study evaluates the effect of different induction courses in children and adolescents with newly diagnosed acute myeloid leukemia. In the first course patients are randomised to receive either standard anthracycline therapy with mitoxantrone or experimental DaunoXome. In the second course patients are randomised between standard treatment with ADxE (cytarabine, DaunoXome, etoposide) or experimental therapy with FLADx (fludarabine, cytarabine, DaunoXome).