45 Clinical Trials for Various Conditions
Pharmacogenomic (PGx) testing involves analyzing variants of genes associated with drug metabolism, transport and medication targets. PGx testing uses an individual's genetic factors, such as single nucleotide polymorphisms (SNPs), to personalize therapy or dose a selection of medications. PGx testing has traditionally been used to test single genes, but there are now platforms allowing a panel of genes to be tested at once. To date there has not been a comprehensive screening of pediatric oncology patients to determine the prevalence of genetic variants that may affect anticancer therapy and supportive care medications. This study would allow us to summarize the frequency of clinically relevant gene-drug interactions and actionable genetic polymorphisms in pediatric oncology patients.
This single arm pilot phase I study with safety run-in is designed to estimate the safety and efficacy of a familial mismatched or haploidentical hematopoietic stem cell transplantation (haplo-HSCT) using a novel graft modification technique (selective αβ-TCR and CD19 depletion).
This phase I trial studies the safety of transplantation with a haploidentical donor peripheral blood stem cell graft depleted of TCRαβ+ cells and CD19+ cells in conjunction with the immunomodulating drug, Zoledronate, given in the post-transplant period to treat pediatric patients with relapsed or refractory hematologic malignancies or high risk solid tumors.
Professional therapeutic boundaries are defined as the limits that protect the space between a professional's power and patient's vulnerability. It is important to develop therapeutic alliances while maintaining boundaries, thus ensuring nurses develop safe connections with patients and their families based on therapeutic needs. Due to the professional nature of nursing, boundary violations are common. For example, closeness and familiarity develops between the healthcare provider, patient, and caregiver that encompass the physical, emotional, and spiritual realms. This provides an opportunity for intense bonds with patients and families. Furthermore in oncology healthcare, providers deliver compassionate care and empathize with patients and families while sharing in the patient's illness journey. As a result of these bonds and relationships the nurse may over disclose personal information, provide excessive patient attention, meeting their own personal needs instead of the patient and family. In addition, continuity of care contributes to boundary crossings because there is frequent repeated contact with the same patients and families which allows blurring of boundary lines. When staff spend weeks, months, or even years with the same patient the opportunity to connect and talk about personal life details exist. At the national level, the National Council of State Boards of Nursing (NCSBN) has created materials for educating nurses in maintenance of therapeutic boundaries. Adherence to therapeutic boundaries has now become an education objective, with the development of educational interventions within many health care settings. Likewise, St. Jude nurses are at an increased risk of crossing therapeutic boundaries due to long term care relationships and vulnerable family members. However, nursing administration has not formally assessed the attributes or behaviors of the nursing staff. This proposal will describe the attributes and behaviors of the St. Jude staff nurse towards nurse-patient/family boundaries, providing knowledge to nursing leadership that will facilitate therapeutic boundaries focus groups with direct care nurses.
There is no curative therapy once acute leukemia patients relapse after transplant. Patients who develop clinically significant graft versus host disease (GVHD) have a lower rate of relapse than those who do not develop GVHD. We are initiating this study of post-transplant fast withdrawal of immunosuppression and donor lymphocyte infusions, with a goal of achieving full donor chimerism in children with hematologic malignancies. If our hypothesis that full donor chimerism results in leukemia-free survival is correct, using immune modulation to achieve full donor chimerism should decrease relapse rate and thus increase survival. The goal of this Phase II study is to identify if achieving full donor chimerism in whole blood CD3+ and leukemia-specific (CD14/15+, CD19+, CD33+ and CD34+) subset may decrease the risk of relapse of patients undergoing allogeneic transplant for hematologic malignancy.
The study participant has one of the following blood cancers: acute myelogenous leukemia (AML)/myelodysplastic syndrome (MDS), acute lymphoblastic leukemia (B-ALL, T-ALL) or Lymphoma. Your cancer has been difficult to treat (refractory) or has come back after treatment (relapse). Primary Objective To determine the safety and maximum tolerated dose of intravenous infusions of escalating doses of CD70-CAR T cells in patients (≤21 years) with recurrent/refractory CD70+ hematological malignancies after lymphodepleting chemotherapy. Secondary Objectives To evaluate the antileukemic activity of CD70-CAR T cells. We will determine the anti- leukemic activity of the CD70-CAR T cells in the bone marrow and in the treatment of extramedullary disease.
This is an open-label, safety study of a single ProHema-CB product administered following myeloablative conditioning regimen in pediatric subjects with hematologic malignancies.
This is a multi-institutional phase II haploidentical T cell replete bone marrow transplant (BMT) study in children with high-risk leukemia. The myeloablative conditioning regimen prescribed will be Total body irradiation (TBI)-based for lymphoid leukemia and busulfan-based for myeloid leukemia. Our goal is to establish an easily exportable, inexpensive platform for haplotransplantation that has a safety profile equivalent to matched related and unrelated BMTs. The primary objective will be to estimate the incidence of 6-month non-relapse mortality (NRM), hypothesizing that NRM is \< 18%.
This is a phase II trial of reduced intensity conditioning with Bu/Flu/ATG in pediatric patients with hematologic malignancies at high risk for transplant related mortality with standard transplantation. Patients qualify based on organ system dysfunction, active but stable infection, history of previous transplant or late stage disease. We plan to enroll 45 patients through the Pediatric Blood and Marrow Transplant Consortium (PBMTC) and anticipate that the outcome of the trial will pave the way for phase II or III disease specific protocols addressing efficacy of the approach compared to standard transplant approaches in better risk patients.
The purpose of the study is to determine the recommended dose of durvalumab and tremelimumab (immunotherapy drugs) in pediatric patients with advanced solid and hematological cancers and expand in a second phase to test the efficacy of these drugs once this dose is determined.
The purpose of this study is to evaluate the safety and the efficacy of SMART101 (Human T Lymphoid Progenitor (HTLP)) injection to accelerate immune reconstitution after T cell depleted allogeneic hematopoietic stem cell transplantation (HSCT) in adult and pediatric patients with hematological malignancies.
Substudy 01A is part of a platform study. The purpose of this study is to assess the efficacy and safety of zilovertamab vedotin in pediatric participants with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), diffuse large B-cell lymphoma (DLBCL)/Burkitt lymphoma, or neuroblastoma and in pediatric and young adult participants with Ewing sarcoma.
This study is a rolling arm study of pembrolizumab in combination with investigational agents in pediatric participants with relapsed or refractory classical Hodgkin lymphoma (cHL) solid tumors with microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) or tumor mutational burden-high (TMB-H). This study will have 2 parts: a safety lead-in to demonstrate a tolerable safety profile and confirm a preliminary recommended phase 2 dose (RP2D) (Part 1) followed by an efficacy evaluation (Part 2). Participants will be assigned to a treatment arm (either Part 1 or Part 2) that is open for enrollment. There will be no hypothesis testing in this study.
The investigators will conduct a pilot feasibility and efficacy trial of a newly developed family health communication tool (called Let's Get REAL) in increasing youth involvement in real-time stem cell transplant and cellular therapy decisions (SCTCT). The investigators will pilot the intervention among 24 youth and their parents, stratified by youth age (stratum 1, 8-12 years of age and stratum 2, 13-17 years of age).
This study is being done to learn more about the short-term and long-term side effects of CAR-T cell therapy. Specifically, researchers want to know how often patients get infections, have delays in recovering blood cell counts and/or have damage to the nervous system.
The participants are being asked to take part in this clinical trial because the participant have a lymphoid or myeloid based cancer diagnosis that requires a bone marrow transplant. Primary Objectives To estimate the incidence of severe acute GVHD (saGVHD) using a prophylaxis regimen with no calcineurin inhibitors after day +60 post first allogeneic Human Leukocyte antigen (HLA)-matched sibling or unrelated donor HCT for hematological malignancies. Secondary objective Determine the cumulative incidence of relapse, NRM, chronic GVHD, and OS in study participants at one year post-transplant. Exploratory objectives * To evaluate the pharmacokinetic/pharmacodynamic (PK/PD) profiles of ruxolitinib, fludarabine, and rATG. * To assess immune reconstitution in study participants within the first year post-HCT.
Tagraxofusp is a protein-drug conjugate consisting of a diphtheria toxin redirected to target CD123 has been approved for treatment in pediatric and adult patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN). This trial aims to examine the safety of this novel agent in pediatric patients with relapsed/refractory hematologic malignancies. The mechanism by which tagraxofusp kills cells is distinct from that of conventional chemotherapy. Tagraxofusp directly targets CD123 that is present on tumor cells, but is expressed at lower or levels or absent on normal hematopoietic stem cells. Tagraxofusp also utilizes a payload that is not cell cycle dependent, making it effective against both highly proliferative tumor cells and also quiescent tumor cells. The rationale for clinical development of tagraxofusp for pediatric patients with hematologic malignancies is based on the ubiquitous and high expression of CD123 on many of these diseases, as well as the highly potent preclinical activity and robust clinical responsiveness in adults observed to date. This trial includes two parts: a monotherapy phase and a combination chemotherapy phase. This design will provide further monotherapy safety data and confirm the FDA approved pediatric dose, as well as provide safety data when combined with chemotherapy. The goal of this study is to improve survival rates in children and young adults with relapsed hematological malignancies, determine the recommended phase 2 dose (RP2D) of tagraxofusp given alone and in combination with chemotherapy, as well as to describe the toxicities, pharmacokinetics, and pharmacodynamic properties of tagraxofusp in pediatric patients. About 54 children and young adults will participate in this study. Patients with Down syndrome will be included in part 1 of the study.
Influenza infection occurring during oncologic treatment or following hematopoietic cell transplantation (HCT) is associated with increased risk of morbidity in the form of lower respiratory tract infection (LRTI) and mortality relative to otherwise healthy patients. The study participants have been diagnosed with a hematological malignancy and are eligible to receive the current seasonal influenza (Flu) vaccine. Primary Objective * To determine the feasibility of opening a longitudinal prospective study of IIV immunogenicity in pediatric leukemia patients. * To describe the immunogenicity, as measured by the development of cell- and/or antibody-mediated influenza specific responses 3 to 5 weeks following vaccination, in a cohort of pediatric leukemia patients. Secondary Objectives * To describe whether an immune response, as measured by development of cell- and/or antibody-mediated influenza specific responses, is detectable 1-2 weeks following vaccination in a cohort of pediatric leukemia patients. * To describe the durability of immunogenicity by measuring cell - and antibody- mediated influenza specific responses at 6 months and 1 year following vaccination in a cohort of pediatric leukemia patients. Exploratory Objectives * To estimate the clinical effectiveness of influenza vaccine in this cohort by monitoring for the development of clinical diagnosis of influenza in the cohort of enrolled pediatric oncology patients. * To correlate results of immune cell frequency in blood, as measured by complete blood count with differential, with development of an immune response to IIV.
This is a first in children prospective study of allogeneic hematopoietic cell transplant using a centrally manufactured engineered donor graft (Orca-Q). The study will assess safety and efficacy of Orca-Q in pediatric patients with hematologic malignancies.
Single-site non-significant risk, open-label clinical investigation designed to validate the usability, adherence, and preliminary diagnostic performance of a novel technology to detect neutropenia. Study participants will be managed as per the standard of care practice with a baseline and nadir visit including laboratory determinations. Participants will also be evaluated with the device at both time points and with daily measurements during the two-week period in between.
This study will validate a previously developed pediatric prognostic biomarker algorithm aimed at improving prediction of risk for the later development of chronic graft-versus-host disease (cGvHD) in children and young adults undergoing allogeneic hematopoietic stem cell transplant. By developing an early risk stratification of patients into low-, intermediate-, and high-risk for future cGvHD development (based upon their biomarker profile, before the onset of cGvHD), pre-emptive therapies aimed at preventing the onset of cGvHD can be developed based upon an individual's biological risk profile. This study will also continue research into diagnostic biomarkers of cGvHD, and begin work into biomarker models that predict clinical response to cGvHD therapies.
Thiotepa is a chemotherapy drug used extensively in bone marrow transplantation. Thiotepa is a prodrug that undergoes metabolic conversion in the liver by CYP2B6 and CYP3A4 to its primary active metabolite, triethylene phosphoramide (TEPA). The goal of this study is to determine what causes some children to have different drug concentrations of thiotepa and TEPA in their bodies and if drug levels are related to whether or not a child experiences severe side-effects during their bone marrow transplant. The hypothesis is that certain clinical and genetic factors cause changes in thiotepa and TEPA drug levels in pediatric bone marrow transplant patients and that high levels may cause severe side-effects.
Melphalan is a chemotherapy drug used extensively in bone marrow transplantation. The goal of this study is to determine what causes some children to have different drug concentrations of melphalan in their bodies and if drug levels are related to whether or not a child experiences severe side-effects during their bone marrow transplant. The hypothesis is that certain clinical and individual factors cause changes in melphalan drug levels in pediatric bone marrow transplant patients and that high levels may cause severe side-effects.
Fludarabine and clofarabine are chemotherapy drugs used extensively in bone marrow transplantation. The goal of this study is to determine what causes some children to have different drug concentrations of clofarabine and fludarabine in their bodies and if drug levels are related to whether or not a child experiences severe side-effects during their bone marrow transplant. The hypothesis is that clinical and individual factors cause changes in clofarabine and fludarabine drug levels in pediatric bone marrow transplant patients and that high levels may cause severe side-effects.
The human microbiome is composed of unique groups of microorganisms occupying distinct habitats distributed throughout the human body. The Human Microbiome Project recently evaluated the bacterial composition of the microbiome in 18 (for women) and 15 (for men) body sites. Much initial attention in the field of microbiome research has focused on the bacterial contribution to a "healthy" microbiome. However, it is clear that other microorganisms, including fungi and viruses, are also distributed throughout the human body and serve as functional components of the microbiome. The populations of microorganisms residing within the oral and nasal cavities make important contributions to human health and disease. These contributions may be especially important in immunosuppressed patients, including those patients receiving myelosuppressive chemotherapy or undergoing hematopoietic stem cell transplantation. In these patients, organisms typically considered as commensals can become pathogenic, either locally or systemically. This observational study is primarily undertaken to evaluate the oral and nasal microbiota and to define the population of fungal organisms residing within the oral and nasal cavities in pediatric oncology patients before and after receiving protocol-directed chemotherapy and associated supportive care.
The goal of this study is to determine whether post-transplant consolidation with azacitidine combined with donor lymphocyte infusion (DLI) is a safe and effective approach for the prevention of relapse in pediatric and young adult patients with hematologic malignancies who have undergone hematopoietic stem cell transplantation (HSCT).
This study will test the safety and effectiveness of adding bortezomib and vorinostat to other chemotherapy drugs commonly used to treat relapsed or refractory leukemia. Both drugs have been approved by the Food and Drug Administration (FDA) to treat other cancers in adults, but they have not yet been approved tor treatment younger patients with leukemia. PRIMARY OBJECTIVE * To estimate the overall response rate of patients with MLL rearranged (MLLr) hematologic malignancies receiving bortezomib and vorinostat in combination with a chemotherapy backbone. SECONDARY OBJECTIVES * Estimate event-free and overall-survival. * Describe toxicities experienced by participants during treatment. OTHER PRESPECIFIED OBJECTIVES * To identify all genomic lesions by comprehensive whole genome, exome and transcriptome sequencing on all patients. * To compare minimal residual disease (MRD) results by three modalities: flow cytometry, polymerase chain reaction (PCR) and deep sequencing.
Background: - Gene therapy involves changing the genes inside the body s cells to stop disease. It is very closely regulated. People who have had this therapy may have problems months or even years later. Researchers do not know the long-term side effects, so they want to study people who have had the therapy. They want the study to continue over the next 15 years. Objective: - To study over time the negative side effects from genetically engineered cellular therapy. This will be studied in people who have been in Pediatric Oncology Branch (POB) gene therapy trials. Eligibility: - People who are currently or were previously in a research study with gene therapy in the National Cancer Institute POB. Design: * Participants blood will be tested right before they get the genetically changed cells. They will get the cells as part of another study. * For the next year, they will come back to the clinic or see their doctor at home at least every 3 months. They will answer questions about their health and blood will be drawn. * For the next 5 years, they will go to the clinic or see their own doctor once a year. They will have physical exam and blood will be drawn. * For 10 years after that, they will be asked every year for health information. * Participants will keep their contact information up to date with researchers. They may be phoned for more health information. * If the participant was under 18 years old when given the gene therapy and turns 18 during this follow-up, they will be asked to sign a new consent form when they turn 18.
Viral infections and reactivation during pediatric allogeneic hematopoietic stem cell transplantation (HSCT) are a common occurrence and significantly contribute to post-transplant morbidity and mortality. The risk is high due to prolonged periods of immune deficiency while awaiting immune reconstitution post-transplant. Current strategies to reduce complications from viral infections include prophylactic treatment, close monitoring for viral infections and prompt treatment at the first sign of symptoms or increasing viral load. However, the most definitive treatment for viral infections remains the host's cellular defenses. Improved understanding of the immune systems response to viral infections may lead to better treatment strategies. This study is being done to explore the relationships between T-cells and NK cells (infection fighting cells) and viral infections or reactivations in young allogeneic stem cell transplant patients. The investigators will be looking at how these cells react and function in young patients receiving allogeneic stem cell transplantation, as well as in healthy stem cell donors.
A subset of patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) harbor rearrangements of the MLL gene, which are detected either by cytogenetic or fluorescent in situ hybridization evaluation at the time of diagnosis. A protein called DOT1L plays an important role in the malignant process in these leukemias. EPZ-5676 is a molecule that blocks the activity of DOT1L, and is therefore being evaluated in the treatment of patients with MLL-rearranged leukemias.