Effect of Pharmacogenetics on Imatinib Plasma Level and Response
Chronic Myeloid LeukemiaImatinib, the tyrosine kinase inhibitor, is used for treatment of Philadelphia positive chronic myeloid leukemia. Despite its efficacy and favorable pharmacokinetic profile, there is a large inter-individual variability in imatinib plasma concentrations, which may lead to treatment failure and disease progression. Polymorphisms in genes related to absorption, distribution, metabolism and excretion of imatinib may affect the bioavailability and consequently the response to the drug. The study aims to investigate the possible effect of genetic polymorphisms in certain metabolizing enzymes [CYP3A5*3 (rs776746), CYP2C8*3 (rs11572080 and rs10509681)] and membrane transporters [ABCB1 2677G>T/A (rs2032582) and SLC22A1 1222A > G (rs628031)] by PCR on the plasma level (by HPLC-UV) and molecular response (MMR) of imatinib in patients with CML. The study also aims to provide CML patients with a personalized treatment option, thereby probably improving the response and reducing the side effects.
Dasatinib Versus Nilotinib for Treatment Naïve Chronic Myeloid Leukemia
Chronic Myeloid Leukemia - Chronic PhaseDANIN study is a randomized, phase 3 clinical trial comparing 'head to head' Nilotinib versus Dasatinib as upfront therapy for patient with chronic myeloid leukemia. The efficacy of both drugs will be tested by measuring BCR/ABL (BCR-ABL = fusion gene from BCR (breakpoint cluster region gene/BCR gene product) and ABL (Abelson proto-oncogene)) using European Leukemia net recommendations the study will be conducted in NCCCR (National Center for Cancer Care & Research) sample size calculations detailed in the statistic part the clinical hematologist will recruit the patients this will include consenting process inclusion and exclusion criteria the molecular pathologist will do the molecular testing the clinical research coordinator and fellows will do the CRF (Case Report Form) as well as quality of life questionnaire and applying the protocol for evaluation of cardiac evaluation Molecular monitoring of BCR-ABL1 transcripts to assess treatment response in CML (Chronic Myeloid Leukemia).
T-cell Depleted Alternative Donor Transplantation
Acute Lymphoblastic LeukemiaAcute Myeloid Leukemia7 moreThe primary purpose is to determine the ability of CD34+ selection and T cell depletion using the CliniMACS® device to prevent severe acute graft-versus-host disease (GVHD) in patients receiving a stem cell transplant from an alternative (unrelated and mismatched related) donor. The secondary objectives include evaluation of engraftment, immune recovery, and post-transplant infections. Patients requiring stem cell transplants for either malignant (cancerous) or non-malignant disease will be included in the study. The recipients will be grouped into one of two groups based on whether the donor is mismatched related (Cohort A) or unrelated (Cohort B). The patient will receive a conditioning regimen including chemotherapy drugs and/or total body irradiation based on the disease for which the transplant is performed.
Ponatinib in Newly Diagnosed Chronic Myeloid Leukemia (CML) (EPIC)
Chronic Myeloid LeukemiaThe purpose of this study is to compare the efficacy of ponatinib and imatinib in patients with newly diagnosed chronic myeloid leukemia (CML) in the chronic phase.
Haploidentical Allogeneic Transplant With Post-transplant Infusion of Regulatory T-cells
LeukemiaAcute6 morePatients with hematologic malignancies will receive myeloablative chemotherapy followed by stem cell rescue with bone marrow or hematopoietic peripheral blood stem cells collected by apheresis from a filgrastim- (G-CSF)-mobilized haploidentical related-donor, ie, hematopoietic peripheral blood stem cell transplant (HSCT).
Hematopoietic Stem Cell Transplantation (HSCT) Using CD34 Selected Mismatched Related Donor and...
LeukemiaLymphocytic14 moreThis study is a means of providing transplantation to those patients who would be a stem cell transplant candidate who do not have an appropriate donor. The use of CD34 selected haploidentical donor with an umbilical cord unit may help provide earlier engraftment without the need for long term immunosuppression. This study tests a new method of bone marrow transplantation called combined haploidentical-cord blood transplantation. In this procedure, some of the blood forming cells (the stem cells) from a partially human leukocyte antigen (HLA) matched (haploidentical) related donor are collected from the blood, as well as cells from an umbilical cord are transplanted into the patient (the recipient) after administration of a "conditioning regimen". A conditioning regimen consists of chemotherapy and sometimes radiation to the entire body (total body irradiation, or TBI), which is meant to destroy the cancer cells and suppress the recipient's immune system to allow the transplanted cells to take (grow).
Clofarabine and Non-Myeloablative Allogeneic Hematopoietic Transplantation
LeukemiaMyelodysplastic Syndrome4 moreAllogeneic hematopoietic transplant is curative for many patients with hematological neoplasms but conditions to provide optimal engraftment and anti-tumor efficacy with minimal toxicity are still under way. Clofarabine is a newly licensed agent with dramatic anti-leukemic activity. Its incorporation into a regimen for pre-transplant conditioning of acute leukemia and lymphoma patients is logical, exploiting both the anti-tumor activities it is recognized to have and the immunosuppressive activity seen with drugs in its class.
Phase 1 Study of Terameprocol (EM-1421) in Patients With Leukemia
LeukemiasAcute Myeloid Leukemia (AML)6 moreThis study is designed to determine the safety, maximum tolerated dose,dose limiting toxicity of Terameprocol(EM-1421)and determine the pharmacokinetics (clearance from the blood)of Terameprocol(EM-1421)given as intravenous infusion three times a week in patients with leukemia.
Trial of Donor Lymphocyte Infusion (DLI) and Activated DLI Following Relapse After Allogeneic Stem...
Chronic Myelogenous LeukemiaAcute Myelogenous Leukemia6 moreThis study is for patients with relapsed of disease after allogeneic bone marrow The donor's T cells are activated by exposure to 2 compounds or antibodies that bind (or stick to) two compounds on T cells called CD3 and CD28. When these antibodies stick to both CD3 and CD28 on the T cells, the T cells becomes stimulated (or "activated") and grows. CD3 and CD28 are the coating of a T cell and a T cell is part of the body's immune system. It is believed that when T cells are exposed to both of antibodies to CD3 and CD28 compounds at the same time, they become activated or "stimulated" and may be more effective in fighting infections or cancer cells. We call this therapy "activated donor lymphocyte infusions, or activated DLI (aDLI)". This current study is being performed to see whether it is safe and effective to administer higher doses of activated DLI or repeated doses of activated DLI. All patients will receive standard donor lymphocyte infusions first, and in addition will receive activated donor lymphocytes approximately 12 days later (DLI followed by aDLI). Depending on the response to this treatment, and depending on possible side effects (such as graft-vs-host disease as described below), patients in remission will then receive additional aDLI every 3 months for 4 more times, and patients not in remission within 6-12 weeks will receive higher dose aDLI. The timing of the higher dose aDLI will be determined by your physician depending on your disease and the rate of progression of your disease. The aDLI can be given as early as 6 weeks, or as late as 12 weeks (3 months).
Bendamustine in Acute Leukemia and MDS
Acute Myeloid LeukemiaMyelodysplastic Syndrome2 moreThe goal of the Phase I part of this clinical research study is to find the highest safe dose of bendamustine that can be given to patients with acute myelogenous leukemia (AML), Acute lymphoblastic leukemia (ALL), Chronic myelogenous (or myeloid) leukemia (CML) in blastic phase, Chronic Myelomonocytic Leukemia (CMML), and myelodysplastic syndromes (MDS). The goal of the Phase II part of this clinical research study is to learn if bendamustine can help to control AML, ALL and MDS. The safety of this drug will continue to be studied.