Clinical Research Directory

Continuous Temperature Monitoring (CTM) for Cytokine Release Syndrome (CRS), an Immune-Related Adverse Event

Background: Drugs or cell therapies to treat cancer can sometimes cause cytokine release syndrome (CRS). That is, the body makes too many cytokines after treatment. Cytokines are proteins that play a role in the immune system. CRS can cause fever, chills, fatigue, low blood pressure, or breathing problems. Researchers want to know if continuously monitoring a person s body temperature can help reduce the chance of getting serious CRS. Objective: To learn if an approved patch called TempTraq can detect fever before serious CRS develops. Eligibility: People aged 18 years and older with cancer who are staying at the NIH clinic for treatment with drugs or cell therapies. Design: Participants will receive TempTraq patches and a special NIH tablet. The TempTraq is a small patch applied to clean, dry skin under the arm. It continually monitors body temperature and sends the data to an application on the tablet. Participants will wear the patch most of the time they are admitted to the hospital. They could wear it for up to 15 days. The patch monitoring does not replace regular temperature checks, all participants will still have have their regular temperature checks as part of their treatment plan. Participants may also opt to use VitalTraq, another application on the tablet. They will hold the screen up to their face for about 1 minute. VitalTraq uses the camera in the tablet to measure blood pressure, heart rate, and breathing. They will do this once per day while they are in the clinic; they may do it more often if they have a fever or feel unwell. Blood may be drawn for research. Participants will be asked about their experience within 1 week after TempTraq is removed. Participants who choose to use the patch, complete its use, and return at a later date for another treatment or study, may be able to re-enroll to have the patch used again.

Phase I Trial of TURALIO(R) (Pexidartinib, PLX3397) in Children and Young Adults With Refractory Leukemias and Refractory Solid Tumors Including Neurofibromatosis Type 1 (NF1) Associated Plexiform Neurofibromas (PN) and Tenosynovial Giant Cell Tumor ...

Background: \- Some people with cancer have solid tumors. Others have refractory leukemia. This may not go away after treatment. Researchers want to see if a drug called TURALIO(R) can shrink tumors or stop them from growing. Objectives: \- To find the highest safe dose and side effects of TURALIO(R). To see if it helps treat certain types of cancer. Eligibility: \- People ages 3-35 with a solid tumor or leukemia that has returned or not responded to cancer therapies. Design: * Individuals will be screened with: * Medical history * Physical exam * Blood and urine tests * Heart tests * Scans or other tests of the tumor * Individuals will take TURALIO(R) as a capsule once daily for a 28-day cycle. They can do this for up to 2 years. * During the study, participants will have many tests and procedures. They include repeats of the screening tests. Individuals will keep a diary of symptoms. * Individuals with solid tumors will have scans or x-rays. * Individuals with leukemia will have blood tests. They may have a bone marrow sample taken. * Some individuals may have a biopsy. * When finished taking TURALIO(R), individuals will have follow-up visits. They will repeat the screening tests and note side effects.

eHealth Mindfulness-based Music Therapy Intervention for Patients Undergoing Stem Cell Transplantation

The goal of this study is to test an electronic health (eHealth) mindfulness-based music therapy intervention to improve health-related quality of life and reduce symptom burden and disease activity in patients undergoing stem cell transplantation.

Electronic Health Mindfulness-based Music Therapy Intervention for Patients Undergoing Allogeneic Stem Cell Transplantation

The goal of this study is to pilot test an Electronic Health Mindfulness-based Music Therapy Intervention (eMBMT) intervention to improve health-related quality of life (HRQoL) and reduce symptom burden of patients undergoing allogeneic stem cell transplantation (allo-SCT).

A Study to Investigate Safety of INT2104 Infusions in Participants Aged 18 Years of Age and Older Who Have B-cell Cancers That Came Back After Previous Treatment

The purpose of this first-in-human study is to evaluate the safety and tolerability of INT2104 when administered to humans in a broad population of participants with refractory/relapsing B-cell malignancies. Preliminary efficacy information may also be obtained. INT2104 is a gene therapy delivering a transgene for a chimeric antigen receptor (CAR) specific for CD20 (CAR20). The lentiviral vector is designed to generate CAR T and CAR Natural Killer (NK) cells inside the body following intravenous (IV) administration. Study details include the following: * The study duration will be 5 years * The treatment duration will be a one-time intravenous (IV) infusion of INT2104

CART123 T Cells in Relapsed or Refractory CD123+ Hematologic Malignancies: A Dose Escalation Phase I Trial

Adult patients with refractory or relapsed CD123+ hematologic malignancies, including acute myeloid leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia, or blastic plasmocytoid dentritic cell neoplasm will be recruited in the trial. CART123 cells will be manufatured from blood of each patient. During the production of CAR123 cells, patients may receive appropriate bridging therapy. After cells are produced, participants will undergo a single course of lymphodepleting chemotherapy and receive a single dose of CAR123 T cells. The trial will establish the recommended dose for further studies, either the Maximum Tolerated Dose (MTD) or Maximum Feasible Dose (MFD). Patients must be eligible for hematopoietic stem cell transplantation in order to participate in the trial.

Efficacy and Safety of Low-dose Chemotherapy Plus Immuno-targeted Drugs in Newly Diagnosed Adult Ph- B-ALL

In the treatment of Ph-negative (Ph-) B-cell acute lymphoblastic leukemia (B-ALL) among adult patients, therapeutic outcomes remain suboptimal despite advances in chemotherapy and immunotherapy. A subset of adults with Ph- B-ALL have comorbidities or physiological limitations that preclude the safe administration of intensive regimens. In recent years, tumor immunotherapy has demonstrated promising safety and efficacy profiles in refractory or relapsed Ph- B-ALL across a wide spectrum of adult ages. These findings suggest that broader application of immunotherapy may represent a critical strategy to improve survival in this population. In this study, we propose a regimen that combines immuno-targeted agents with low-intensity chemotherapy for newly diagnosed adult patients with Ph- B-ALL. Our primary objective is to increase the rate of measurable residual disease (MRD)-negative complete remission (CR) following induction therapy, reduce the risk of relapse, and ultimately enhance overall survival.

Phase I Clinical Trial of CART Cell Therapy for Refractory/Relapsed Acute Lymphoblastic Leukemia in Children, Adolescents and Young Adults

The goal of this clinical trial is to test the feasibility and safety of an academic production of two different anti-CD19 chimeric antigen receptor T cells (CART) products according to the different biomarkers of the disease in children and young adults with relapsed/refractory CD19+ B cell acute lymphoblastic leukemia (r/r B-ALL) or relapsed/refractory T-cell acute lymphoblastic leukemia (r/r T-ALL). The main questions it aims to answer are: 1. The safety and feasibility of autologous CART-19/22 in children, adolescents and young adults with a CD19+/- CD22+ relapse/ refractory disease for a r/r B-ALL. 2. The safety and feasibility of allogeneic CART-NKG2D (chimeric-antigen receptor Natural-killer group 2, member D) in children, adolescents and young adults with r/r T-ALL.

Pediatric-inspired Regimen Combined With Venetoclax for Adolescent and Adult Patients With de Novo Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia

The pediatric-inspired regimen has greatly improved the prognosis of adult patients with with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL), but relapse remains a great challenge. Venetoclax (Ven) is an oral, selective inhibitor of B-cell lymphoma 2 (Bcl-2). Although this drug is currently used primarily for acute myeloid leukemia, in vitro as well as small cohort studies suggest a effect in acute lymphoblastic leukemia. This study proposes to combine pediatric-inspired regimen with venetoclax for the treatment of adult patients with Ph- ALL, aiming to improve the MRD-negative complete remission rate measured by flow cytometry after induction and to reduce relapse, thus further improving patients overall survival.

Effectiveness of Probiotics for the Prevention of Gastrointestinal Toxicity in Children With Leukemia

Background: Acute lymphoblastic leukemia (ALL) is a common malignant neoplasm in children. Although chemotherapy achieves remission in over 70% of cases, it can cause gastrointestinal toxicity in up to 32.5%. Some studies suggest that administering probiotics reduces this risk, but the evidence remains inconsistent. Objective: To evaluate the effectiveness and safety of administering L. casei, L. rhamnosus or B. bifidum compared to a placebo for the prevention of gastrointestinal toxicity, decreased intestinal permeability, and changes in intestinal microbiota in pediatric patients diagnosed with acute lymphoblastic leukemia receiving chemotherapy. Methods: A total of 120 participants aged 6 to 17 years, diagnosed with ALL and receiving consolidation phase chemotherapy without gastrointestinal comorbidities, will be included. Participants will be administered daily 2 capsules containing either 1) L. casei, 2) L. rhamnosus, 3) B. bifidum or 4) placebo daily for 8 weeks. The clinical status of the participants will be evaluated weekly by the oncology service to determine the presence of gastrointestinal toxicity and adverse events. Changes in intestinal permeability will be assessed by measuring beta-lactoglobulin in a blood sample using the ELISA technique, while changes in the intestinal microbiota will be analyzed by genomic sequencing at baseline and at the end of follow-up. Statistical analysis: Descriptive analysis will use measures of central tendency and dispersion. For quantitative variables, the mean and standard deviation or median with minimum and maximum values will be calculated depending on the distribution type. Frequencies and proportions will be calculated for qualitative variables, presented in tabular and graphical form. To compare the quantitative variables between the four interventions, a multi-way ANOVA test will be used. The risk of gastrointestinal toxicity and adverse events will be analyzed by calculating the relative risk and 95% confidence interval. Differences between the interventions will be analyzed using survival analysis with the Kaplan-Meier and Log-Rank tests. Sequencing data will be analyzed using the Qiime2 program, filtered to generate a phylogenetic tree using the Silva database. Corresponding plots will be generated for each taxonomic level. Alpha (intra-group) and Beta (inter-group) diversity will be presented by ordination plots using principal component analysis with the ANCOM program

Glucose Intolerance and Diabetes Related to Treatment With Steroids and PEG- Asparaginase in Children and Adolescents With ALL and Lymphoma

The overall survival of acute lymphoblastic leukemia (ALL) and lymphoma in children and adolescents is above 90%. The survival rate has increased significantly during the last decades as a consequence of more intensive chemotherapy. This very toxic treatment results in severe acute toxicities and late effects, which is the biggest challenge today besides survival. The overall purpose of contemporary ALL treatment is to reduce the toxic treatment without compromising the excellent survival rates of these diseases. This study is a part of this. The researchers want to investigate the incidence of glucose intolerance and medicine induced diabetes during treatment for ALL and lymphoma with steroids (prednisolone or dexamethasone) and ± PEG-asparaginase. Steroids and asparaginase are used in the treatment of ALL and lymphomas, and both drugs may induce glucose intolerance or diabetes, especially when they are given concomitantly. The incidence and duration of increased blood glucose levels are not very well investigated, and especially not monitored continuously during treatment phases with steroids and +/- asparaginase, as the investigators want to do in this study. In the study the participants must have a glucose sensor attached under the skin, which continuously measures blood glucose during treatment. Moreover, blood samples are drawn several times to measure insulin sensitivity and beta cell function. The participants are children and adolescents (1.0-17.9 years) with newly diagnosed ALL or lymphoma treated at one of the four Danish pediatric oncology sites. Blood glucose levels are followed during treatment with steroids and PEG-asparaginase in these patient groups. The results may give rise to a new treatment guidelines for measuring and treating blood glucose in these patients. In the future this may help reduce the development of type 2 diabetes mellitus and metabolic syndrome in survivors of ALL and lymphoma.

MRD-associated Non-intensive But Non-interruptive Treatment of Ph-negative Acute Lymphoblastic Leukemia Adult Patients

Non-intensive But Non-interruptive Treatment based on previously study RALL-2016 of Adult Ph-negative Acute Lymphoblastic Leukemia: No high-dose methotrexate (MTX) and high-dose cytarabine (ARA-C) consolidation blocks, L-asparaginaseis scheduled for 1 year of treatment, 21 intrathecal injections through the whole treament, T-ALL patients in complete remission (CR) with MRD-positive status after 2nd induction receive consolidation 1-3 with venetoclax (56 days), and B-ALL patients in complete remission (CR) with MRD-positive status after 2nd induction receive 1 consolidation with blinatumomab. After that consolidation bone samples are collected and tested for MRD and patients will continue therapy by protocol without HSCT if MRD-negative (by flow cytometry by aberrant immunophenotype in a centralized lab) status was achieved.