217 Clinical Trials for Various Conditions
Blood and marrow stem cell transplant has improved the outcome for patients with high-risk hematologic malignancies. However, most patients do not have an appropriate HLA (immune type) matched sibling donor available and/or are unable to identify an acceptable unrelated HLA matched donor through the registries in a timely manner. Another option is haploidentical transplant using a partially matched family member donor. Although haploidentical transplant has proven curative in many patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including GVHD and infection due to delayed immune reconstitution. These can, in part, be due to certain white blood cells in the graft called T cells. GVHD happens when the donor T cells recognize the body tissues of the patient (the host) are different and attack these cells. Although too many T cells increase the possibility of GVHD, too few may cause the recipient's immune system to reconstitute slowly or the graft to fail to grow, leaving the patient at high-risk for significant infection. For these reasons, a primary focus for researchers is to engineer the graft to provide a T cell dose that will reduce the risk for GVHD, yet provide a sufficient number of cells to facilitate immune reconstitution and graft integrity. Building on prior institutional trials, this study will provide patients with a haploidentical (HAPLO) graft engineered to specific T cell target values using the CliniMACS system. A reduced intensity, preparative regimen will be used in an effort to reduce regimen-related toxicity and mortality. The primary aim of the study is to help improve overall survival with haploidentical stem cell transplant in this high risk patient population by 1) limiting the complication of graft versus host disease (GVHD), 2) enhancing post-transplant immune reconstitution, and 3) reducing non-relapse mortality.
Blood and marrow stem cell transplant has improved the outcome for patients with high-risk hematologic malignancies. However, most patients do not have an appropriate HLA (immune type) matched sibling donor available and/or are unable to identify an acceptable unrelated HLA matched donor through the registries in a timely manner. Another option is haploidentical transplant using a partially matched family member donor. Although haploidentical transplant has proven curative in many patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including graft versus host disease (GVHD) and infection due to delayed immune reconstitution. These can, in part, be due to certain white blood cells in the graft called T cells. GVHD happens when the donor T cells recognize the body tissues of the patient (the host) are different and attack these cells. Although too many T cells increase the possibility of GVHD, too few may cause the recipient's immune system to reconstitute slowly or the graft to fail to grow, leaving the patient at high-risk for significant infection. This research project will investigate the use of particular pre-transplant conditioning regimen (chemotherapy, antibodies and total body irradiation) followed by a stem cell infusion from a "mismatched" family member donor. Once these stem cells are obtained they will be highly purified in an effort to remove T cells using the investigational CliniMACS stem cell selection device. The primary goal of this study will be to determine the rate of neutrophil and platelet engraftment, as well as the degree and rate of immune reconstitution in the first 100 days posttransplant for patients who receive this study treatment. Researchers will also study ways to decrease complications that may occur with a transplant from a genetically mismatched family donor.
The main purpose of the study was to investigate whether nilotinib treatment can be safely suspended with no recurrence of CML in selected patients who responded optimally on this treatment
This study will try to improve the safety and effectiveness of stem cell transplant procedures in patients with cancers of the blood. It will use a special machine to separate immune cells (T cells) from the blood of both the donor and the patient and will use photodepletion, a laboratory procedure that selectively kills cancer cells exposed to light. These special procedures may reduce the risk of graft-versus-host-disease (GVHD), a serious complication of stem cell transplants in which the donor's immune cells destroy the patient's healthy tissues, and at the same time may permit a greater graft-versus-leukemia effect, in which the donated cells fight any residual tumor cells that might remain in the body. Patients between 18 and 75 years of age with a life-threatening disease of the bone marrow (acute or chronic leukemia, myelodysplastic syndrome, or myeloproliferative syndrome) may be eligible for this study. Candidates must have a family member who is a suitable tissue match.
The purpose of this prospective, single-institution observational study is to evaluate associations between the pharmacokinetic (PK) parameters for tyrosine kinase inhibitors (TKIs) used to treat chronic phase chronic myeloid leukemia (CML) and clinical outcomes for up to 12 months. The study aims to identify associations between TKI clearance and/or exposure with demographic and clinical patient characteristics, CML milestones, medication toxicities, medication adherence, and germline genetic variants. Because this is an observational study, standard-of-care therapy will not be altered during the course of participation. Blood samples will be collected at each study visit (up to 6 visits) over the course of 12 months to evaluate TKI concentrations, and PK parameters. Blood will also be collected during the first visit to isolate DNA for next generation sequencing (NGS). Demographic information will be collected at baseline, while clinical and medication adherence information will be collected at baseline and then throughout the study. There will be no direct benefit to you for your participation. Risks are minor, but could include bruising, vein irritation, lightheadedness/dizziness, and/or infection from blood draws, as well as potential loss of confidentiality.
Allogeneic hematopoetic stem cell transplantation (SCT) is frequently complicated by life threatening viral reactivation. Conventional antiviral therapy is suboptimal for cytomegalovirus (CMV), adenovirus (AdV) and Epstein-Barr virus (EBV) and nonexistent for BK virus (BKV). An alternative approach to prevent viral reactivation is to infuse virus-specific cytotoxic T cells (CTL) prepared from the donor early after SCT. Such multivirus-specific CTL cells (MVST) have been successfully used in a number of centers to prevent or treat CMV, Ad and EBV. Activity of BKV-reactive cells has not been studied. Multi virus-specific T cells (MVST) are donor lymphocytes that are highly enriched for viral antigens and expanded in vitro before infusion into the transplant recipient. Viral reactivation is a particular problem inT cell depleted SCT. Median time to CMV reactivation is estimated as 28 days post T-depleted transplant, but infusion of MVST within the immediate post-SCT period has not been previously studied. This protocol will be the first of a planned series of cellular therapies to be layered on our existing T lymphocyte depleted transplant platform protocol 13-H-0144. The aim of this study is to determine the safety and efficacy of very early infusion of MVST directed against the four most common viruses causing complications after T-depleted SCT. GMP-grade allogeneic MVST from the stem cell donor will be generated using monocyte-derived donor dendritic cells (DCs) pulsed with overlapping peptide libraries of immunodominant antigens from CMV, EBV, Ad, and BKV and expanded in IL-7 and IL-15 followed by IL-2 for 10-14 days. A fraction of the routine donor leukapheresis for lymphocytes obtained prior to stem cell mobilization will be used to generate the MVST cells. MVST passing release criteria will be cryopreserved ready for infusion post SCT. Eligible subjects on NHLBI protocol 13-H-0144 will receive a single early infusion of MVST within 30 days (target day +14, range 0-30 days) post SCT. Phase I safety monitoring will continue for 6 weeks. Viral reactivation (CMV, EBV, Ad, BK) will be monitored by PCR by serial blood sampling. The only antiviral prophylaxis given will be acyclovir to prevent herpes simplex and varicella zoster reactivation. Subjects with rising PCR exceeding threshold for treatment, or those with clinically overt viral disease will receive conventional antiviral treatment. Patients developing acute GVHD will receive standard treatment with systemic steroids. These patients are eligible for reinfusion of MVST when steroids are tapered. The clinical trial is designed as a single institution, open label, non-randomized Phase I/II trial of MVST in transplant recipients, designed as 3-cohort dose escalation Phase I followed by a 20 subject extension Phase II at the maximum tolerated dose of cells. Safety will be monitored continuously for a period of 6 weeks post T cell transfer. The primary safety endpoint will be the occurrence of dose limiting toxicity, defined as the occurrence of Grade IV GVHD or any other SAE that is deemed to be at least probably or definitely related to the investigational product. The primary efficacy endpoint for the phase II will be the proportion of CMV reactivation requiring treatment at day 100 post transplant. Secondary endpoints are technical feasibility of MSVT manufacture, patterns of virus reactivation by PCR, and clinical disease from EBV, Ad, BK, day 100 non-relapse mortality.
Background: - People who have some kinds of cancer can benefit from donated bone marrow stem cells. These stem cells help produce healthy bone marrow and slow or stop the spread of abnormal cells. However, stem cells transplants do not always work. Also, they may have serious side effects that can cause illness or death. The Bone Marrow Stem Cell Transplant Program is studying methods to make stem cell transplant procedures safer and more effective. Objectives: - To test a new procedure that may improve the success and decrease the side effects of stem cell transplants. Eligibility: * Individuals 10 to 75 years of age who have a life-threatening illness that may require a stem cell transplant. * Healthy siblings who are able to provide stem cells for transplant. Design: * Participants will be screened with a medical history, physical exam, and blood and urine tests. * Donor procedures: * Stem cell donors will start by having apheresis to donate white blood cells. * Donors will receive filgrastim shots for 5 days to help move stem cells into the blood for collection. * Donors will have another round of apheresis to donate the stem cells for transplant. * Recipient procedures: * Before the transplant, recipients will have radiation twice a day for 3 days and chemotherapy for 7 days. * After the radiation and chemotherapy, recipients will receive the stem cells provided by the donor. * After the transplant, recipients will receive the white blood cells provided by the donor. * Recipients will be monitored closely for 4 months to study the success of the transplant. They will have more followup visits at least yearly thereafter. * Recipients will have a research apheresis prior to transplant and at 3 months.
This study is to determine the number of European Leukemia Network (ELN)guideline defined treatment failure events from time of study entry in CML-CP patients with low imatinib trough concentrations treated with nilotinib.
Background: * Most patients with acute lymphoblastic leukemia (ALL) and many patients with acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML) and non-Hodgkin's lymphoma (NHL) have a protein called Wilm's Tumor 1 (WT1) in their cancer cells. This protein is thought to be able to influence the growth of these cancers. * A vaccine made with the WT1 protein may boost the immune system to help fight these cancers in patients whose cancer cells contain the protein. Objectives: * To determine the safety, effectiveness and side effects of giving the WT1 vaccine and donor white blood cells to patients with AML, ALL, CML or NHL who have previously received standard treatment and undergone stem cell transplantation. * To determine the immune response to the WT1 vaccine and donor white blood cells in these patients and to determine if the response is related to the amount of WT1 protein in the patient's cancer cells. Eligibility: * Patients between 1 and 75 years of age with the blood antigen human leukocyte antigen (HLA-A2) and the WT1 cancer protein who have persistent or recurrent blood cancers after stem cell transplantation. * The prior stem cell transplant donor must be willing to provide additional cells, which will be used to prepare the cellular vaccines and for donor lymphocyte (white blood cell) infusions. Design: * Patients are given the WT1 vaccine every 2 weeks for 6 weeks (weeks 0, 2, 4, 6, 8, 10). Each vaccination consists of two injections in the upper arm or thigh. * On weeks 0, 4 and 8, patients also receive white blood cells from a donor to enhance the immune response. The cells are also given as a 15- to 30-minute infusion through a vein about 1 hour after the vaccine injection. Donor infusions are given only to patients with mild or no graft-vs-host disease resulting from their prior stem cell transplantation. * Periodic physical examinations, blood and urine tests, scans to evaluate disease and other tests as needed are done for 12 months after enrollment in the study.
To evaluate molecular relapse free rates 6 months after stopping nilotinib therapy in patients who achieve MR4.5
The study is a Phase II clinical trial. Patients will receive intensity-modulated total marrow irradiation (TMI) at a dose of 9 Gray (Gy) with standard myeloablative fludarabine intravenous (IV) and targeted busulfan (FluBu4) conditioning prior to allogeneic hematopoietic stem cell transplant (HSCT). Graft-versus-host disease (GVHD) prophylaxis will include Cyclophosphamide on Day +3 and +4, tacrolimus, and mycophenolate mofetil.
This study will be a multicenter Phase IIIb open-label, three-cohort study of asciminib in patients with CML-CP without T315I mutation who have had at least 2 prior TKIs and CML-CP harboring the T315I mutation with at least 1 prior TKI
To evaluate efficacy, safety and pharmacokinetic profile of asciminib 40mg+imatinib or asciminib 60mg+imatinib versus continued imatinib and versus nilotinib versus asciminib 80mg in pre-treated patients with Chronic Myeloid Leukemia in chronic phase (CML-CP)
The objective of this study is to establish the performance of an assay that detects mRNA transcript levels in patients diagnosed with CML. The study is conducted at locations within the United States. Testing is performed on peripheral blood specimens provided by eligible enrolled patients. Results from this study will not be used for patient management decisions.
To satisfy a postmarketing requirement, the sponsor has been requested to conduct a Phase 1/Phase 2 single-group clinical study to investigate the pharmacokinetics and preliminary safety and efficacy of omacetaxine following a fixed-dose administration to patients with CP or AP CML who have failed 2 or more tyrosine kinase inhibitor (TKI) therapies.
The objective of the study is to provide long term access to bosutinib treatment and assess long term safety, tolerability and duration of clinical benefit, without any formal hypothesis testing; therefore, there is no formal primary endpoint.
To evaluate the safety, efficacy and pharmacokinetics of nilotinib over time in the Ph+ chronic myelogenous leukemia (CML) in pediatric patients (from 1 to \<18 years).
This study is designed to determine the maximal tolerated dose of Ruxolitinib in combination with nilotinib in patients with chronic myeloid leukemia (CML).
The 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.
The purpose of this study is to test the hypothesis that patients with CML who have not achieved optimal response after 3 months of treatment with imatinib will have a better response by switching to dasatinib compared to staying on their original imatinib regimen.
The goal of this clinical research study is to learn if ponatinib can help to control Chronic Myeloid Leukemia (CML) in accelerated phase. The safety of this drug will also be studied. Ponatinib is designed to block the function of BCR-ABL, which is the abnormal protein responsible for causing leukemia in certain cells. Ponatinib may cause a blood clot to form in an artery or in a vein. Depending on the location of the clot, this could cause a heart attack, a stroke, severe damage to other tissue, or death. A blood clot may occur within 2 weeks after you start taking the drug. About 25% (1 in 4) of patients taking the drug form an abnormal clot. Blood clots can occur in patients that do not have other known risk factors for forming clots. If you develop a blood clot, you will need to stop taking ponatinib. In some cases, emergency surgery could be needed to remove the clot and restore blood flow.
This study is being conducted in a population of patients with chronic phase Chronic Myeloid Leukemia (CML) to learn more about how patients follow prescribed regimens for taking oral cancer drugs.
This is a 2 part study. The goal of the first part of this clinical research study is to find the highest tolerable dose of azacitidine that can be given with a TKI that you are already taking (such as Gleevec, Sprycel, or Tasigna). The safety of this drug will also be studied. The goal of the second part is to see if this combination may improve your response to the TKI you are already taking. Azacitidine is designed to change genes that are thought to cause leukemia. By changing these genes, the drug may help to stop them from causing the disease to grow.
In this research study, the investigators are looking to see whether the combination of arsenic trioxide with a tyrosine kinase inhibitor is safe, and what effects it has on chronic myelogenous leukemia.
The goal of this clinical research study is to learn if adding pegylated interferon-alfa 2a (Pegasys) to the TKI that you are already receiving can help to control CML. The safety of this treatment combination will also be studied. Pegasys is a form of the drug interferon. It is designed to help the body's immune system to fight infections. It may also affect the body's response to cancer. A TKI (imatinib mesylate, nilotinib, or dasatinib) is designed to bind to and shut off a protein in tumor cells called Bcr-Abl. Shutting Bcr-Abl off may prevent CML cells from growing, and may cause them to die. You are already receiving a TKI. This consent form will describe the administration of Pegasys, any tests and procedures that need to be performed while you are receiving Pegasys, and any risks/benefits there may be from receiving Pegasys.
The purpose of this study is to better understand the use of tyrosine kinase inhibitors (TKI) in patients newly diagnosed with CML and their quality of life in a real-world setting.
The purpose of the study is to determine the safety and tolerability of the combination of BMS-833923 plus dasatinib in patients with chronic myeloid leukemia.
Objectives: The objective of this study is to measure and delineate the symptom burden experienced by patients with chronic myeloid leukemia (CML). The Primary Aim is to develop and validate an M. D. Anderson Symptom Inventory (MDASI) module (the MDASI-CML), compliant with FDA standards for patient-reported outcomes (PROs), to measure the severity of multiple symptoms and the impact of these symptoms on daily functioning in patients with CML. The Secondary Aims are: 1. to develop a detailed description of the severity and interference with daily activities of symptoms experienced by patients with CML; 2. to assess the impact of symptom severity in CML on standard functioning and quality of life (QOL) measures including Eastern Cooperative Oncology Group (ECOG) Performance Status and single-item QOL scale; 3. to evaluate the MDASI-CML as an estimate of functional status and QOL in patients with CML; 4. to identify common clusters of symptoms and symptom patterns occurring over multiple measurement time points in patients with CML; 5, to define the qualitative symptom burden of patients with CML; 6. to explore the feasibility of the Interactive Voice Response (IVR) system in measuring symptom severity and interference with daily activities over time in patients with CML.
The aim of this study is to test the effect of the combination of valproate in combination with imatinib with an aim of achieving a maximal molecular response as the primary goal.
In this study researchers propose to do a chart review of all patients that are treated outside of a clinical trial with imatinib, dasatinib, nilotinib, or any other tyrosine kinase inhibitor that becomes FDA approved for the managements of CML that come to MDACC for a second opinion. This is an important population of patients that differs in their management from patients treated in clinical trials for several reasons including but not limited to: 1. It represents a very large patient population receiving standard-dose therapy with TKI. We estimate that we have evaluated over 300 patients that fall in this category. 2. The follow-up for patients in the largest trial using standard-dose imatinib (the IRIS trial, with 553 patients in treated with imatinib) has been limited after the first 12 months. For example, the rate of molecular responses after the first 12 months of therapy was not obtained as samples stopped being collected at that time point. 3. Registration studies for dasatinib and nilotinib have similar limitations with limited follow-up and available information coming only from databases from the sponsors to which there is limited access to investigate dosing, chronic toxicities, second malignancies and other important aspects of therapy. 4. Patients who are or become pregnant during therapy with TKI have not been eligible for clinical trials with TKI or had to be taken off study. Thus, there is no information on the effect of TKI on imatinib on pregnancy and conception. We have followed several such patients at MDACC. 5. This is a patient population that follows therapy mostly as directed by their local oncologists. This is frequently less stringently adhered to the recommended guidelines for TKI therapy, with more frequent treatment interruptions, and frequently using suboptimal doses of imatinib (i.e., less than 300mg daily). The effect of these treatment interruptions and suboptimal dosing on response and development of resistance is unclear. Researchers plan to conduct a chart review of these patients to study their treatment course before their initial evaluation at MDACC, and between and during visits to MDACC.