Clinical Research Directory

Cognitive Aftereffects of Neurotoxicity in Children and Young Adults With Relapsed/Refractory Hematologic Malignancies Who Receive CAR T-cell Therapy

Background: CAR T-cell therapy is a promising new treatment for blood cancers. During treatment, a person s T-cells are genetically changed to kill cancer cells. Researchers want to learn more about the effects of potential problems that may be associated with this treatment. We are specifically interested in learning if and how this treatment may affect the brain or your thinking skills. Objective: To learn if CAR T-cell therapy can affect how children and adults think, process, and remember things. Eligibility: People aged 5-35 who have blood cancer that has not responded to treatment, or the blood cancer has come back after treatment, and who will receive CAR T-cell therapy. Caregivers are also needed. All participants must be able to speak and read in English or Spanish. Design: Participants will be screened with a medical history. Information from participants medical records will be collected. Participants will take tests at home or at NIH to see how well they think, read, learn, remember, reason, and pay attention. The tests will be both computerized and paper/pencil. They will take less than 1 hour to complete. Participants and a parent/adult observer will complete a 5-minute Background Information Form and a checklist of nervous system symptoms. If participants are 5 years or older, they will participate in activities to test their ability to do different thinking tasks, like answer questions, complete puzzle patterns, and remember things. Participants and their caregivers will complete questions to see if they are having specific symptoms related to receiving CAR T-cells. The questions will assess their well-being and needs. The questions will take less than 1 hour to complete. Some tests and questions will be repeated at different time points in the study. Participation will last for up to 3 years....

The Value of a Tailored-based, Exercise Program for Improving Quality of Life of Patients With Hematologic Malignancies: a Pilot Randomized Trial

This multicenter, prospective, pilot randomized controlled trial aims to evaluate the feasibility and preliminary efficacy of a 16-week structured exercise program (SEP) in patients with hematologic malignancies, including acute myeloid leukemia, lymphoma, and multiple myeloma. A total of 75 patients will be randomized in a 1:1 ratio to either a supervised exercise intervention or a control group receiving usual care and general advice on physical activity. The intervention consists of a personalized, hybrid exercise program combining supervised home- and gym-based training, aerobic and resistance exercises, balance and stretching activities, and behavioral counseling. The primary objective is to assess the feasibility of the intervention in terms of adherence to the exercise program and patient satisfaction. Secondary objectives include evaluating intervention-related adverse events, patient-reported burden, health-related quality of life, fatigue, physical fitness, anthropometric parameters, and physical activity levels. Assessments will be conducted at baseline, approximately 8 weeks, 16 weeks (end of intervention), and 24 weeks after randomization.

Evaluation of LB-208 (HTR1B Antagonist) in Adult Patients With Relapsed or Refractory Solid Tumours and Lymphoma

This clinical study is investigating a new experimental medicine called LB-208, developed for the treatment of advanced solid tumors and lymphomas in adult patients whose disease has relapsed, not responded to treatment, or for whom no suitable standard treatment option remains. This is a Phase I trial, meaning it is an early-stage study in humans. At this stage, the main goal is not yet to prove definitive effectiveness, but rather to better understand the safety of the medicine, how it behaves in the body, and what dose may be most appropriate for future studies. LB-208 is an oral compound that works by blocking a target called HTR1B. According to the protocol, it is considered a first-in-class treatment, meaning it belongs to a new therapeutic category and has a novel mechanism of action in this setting. The drug is given orally, once a day, under fasting conditions, in continuous 28-day cycles, with no breaks between cycles. The study is open-label and uses a dose-escalation design. This means that both the medical team and the patients know which treatment is being given, and that the first groups of patients receive lower doses, which are gradually increased if tolerance is acceptable. The design used is the well-known 3+3 model: initially, 3 patients are treated at a given dose level. If no major safety concerns are seen, the dose is increased for the next group. If significant side effects appear, more patients may be enrolled at the same dose level or the escalation strategy may be adjusted. This approach helps identify the maximum tolerated dose and the recommended dose for future studies. The main objective of the trial is to assess the safety and tolerability of LB-208 and determine the dose that can be recommended for further clinical development. To do this, researchers closely monitor adverse events, laboratory test results, physical examinations, vital signs, electrocardiograms, and other clinical parameters. A particularly important part of the study is the identification of dose-limiting toxicities (DLTs), which are significant side effects occurring during the first treatment cycle and help define whether a dose is tolerable. In addition to safety, the study also examines pharmacokinetics, meaning how the medicine is absorbed, distributed, metabolized, and eliminated by the body. Blood samples are collected at different time points to measure how much LB-208 is present in the bloodstream and for how long. This information is essential to understand how the treatment works in practice and to help optimize dosing. The study also includes pharmacodynamic and exploratory biomarker analyses. These assessments aim to better understand whether the medicine is having the expected biological effect and whether there are tumor or blood markers that may help identify patients more likely to benefit from treatment in future studies. Although this early trial is not primarily designed to prove anti-tumor efficacy, researchers will also evaluate preliminary signs of clinical activity, such as tumor shrinkage, disease stabilization, duration of response, and progression-free survival. Patients taking part in the study must meet a series of eligibility criteria. In general, they must be adults with advanced cancer for which standard options are no longer effective or appropriate, have a good enough general condition to undergo experimental treatment, and meet the required organ function and laboratory parameters. As in all clinical trials, there are also exclusion criteria intended to protect patient safety, such as certain uncontrolled medical conditions, specific previous treatments, or other factors that could interfere with interpretation of the results. Participation in this trial may offer some patients access to an innovative therapy that is not otherwise available. However, because it is a Phase I study, there are also important uncertainties. The benefits cannot be guaranteed, the most appropriate dose is still being defined, and unexpected side effects may occur. For this reason, patients are followed very closely by the clinical team throughout the study. Overall, LB-208 / SERONCO-1 is an early clinical study designed to determine whether this new oral HTR1B inhibitor can be administered safely, to define the best dose for future development, and to generate the first clinical information on its potential role in treating advanced cancer. The knowledge gained from this study may help guide the next stages of development and determine whether LB-208 should move forward into later-phase trials.

Stem Cell Transplantation for Participants With Germline RUNX1 Associated Blood Cancers

Background: Some blood cancers can be caused by germline variants (changes) in a person s RUNX1 gene. Germline variants are genetic inherited changes a person is born with. Stem cell transplants are used to treat many diseases including blood cancers. Stem cell transplantation for patients with germline RUNX1 mutation driven blood cancers is standard of care and available in most major medical centers. The difference with this transplantation protocol is that it is prospective, only available to participants with germline RUNX1 variants and designed to determine the extent to which tailoring chemotherapy and supportive care medication doses for each individual patient may improve outcomes compared to data derived from retrospective transplantation protocols for patients with RUNX1 varinats which is less accurate. Objective: The primary objective of this protocol is to determine how tailored doses of chemotherapy and supportive care medications may improve disease free survival as compared to historical/expected disease free survival. Eligibility: People aged 4 to 70 years with blood cancer caused by a RUNX1 gene mutation. Other participants are also needed: (1) stem cell donors; (2) relatives who do not have a mutation in the RUNX1 gene; and (3) healthy volunteers. Design: Participants with blood cancer will be screened during approximately 1-3 months before transplatation. They will have blood tests and tests of their heart and lung function. A sample of bone marrow may be taken. A flexible tube (central line) will be inserted into a vein in participants' chest or lower neck. This line will remain in place during the hospitalization and be used to draw blood and administer drugs. These lines are almost always transitioned to a peripherally inserted central catheter (PICC) line at the time of hospital discharge. Participants will be inpatient for 4 to 5 weeks. They will receive drugs to prepare their body for the stem cell transplant. Some may also receive radiation treatment. Other tests will include imaging scans. The stem cell transplant will be given through the central line. After discharge from the clinic, participants will have follow-up visits at least once per week for approximately 100 days. Then they will have follow-up clinic visits for 3 years. Donors, relatives, and healthy volunteers may provide samples of blood, stool, and saliva. Adults may also opt to provide samples of skin and bone marrow.

A Phase 1/2, Open-label Study of Valemetostat in Combination With Rituximab and Lenalidomide in Relapsed or Refractory Follicular Lymphoma

To find a recommended dose of valemetostat that can be given in combination with rituximab and lenalidomide to patients with follicular lymphoma. The safety and effects of this drug combination will also be studied

Mosaic Trial for Stem Cell Transplant Recipients

The goal of this clinical trial is to learn if using an intervention website (Mosaic) improves selected patient-reported outcomes in adult blood cancer patients undergoing allogeneic or autologous stem cell transplant, compared to using an educational website (control group). Patients will be recruited prior to their scheduled transplant, then randomized to use one of these two study websites throughout the study. They will complete five assessments during the study: one before transplant (baseline) and four after transplant (2, 4, 6, and 8 month follow-ups). The main questions this trial aims to answer are: 1. Compared to patients using the control group website, do patients using the intervention website report greater improvements in general psychological distress, cancer treatment-related distress, physical symptoms, and health-related quality of life? 2. Are these benefits at least partially explained by improvements in perceived preparedness, self-efficacy, and approach coping and/or reductions in avoidant coping and perceived stress? 3. Do some patients benefit more from using the intervention website than others? Specifically, we will examine whether patients' primary language (English/Spanish) and their initial psychological distress are related to the benefit they get from using the intervention website. We will also explore effects of sex, race, ethnicity, and transplant type.

More Than Just X-Rays - Imaging of Chemotherapy-induced Morphological and Functional Cardiovascular and Lung Changes After Childhood ALL and Other Cancers - a Monocentric Late Effects Study (MaximALL)

In this study, we investigate the cardiopulmonary health of survivors who underwent cancer treatment for acute lymphoblastic leukemia (ALL) or lymphoma during childhood, compared with healthy controls. Modern imaging techniques (MRI, MSOT, and echocardiography) as well as questionnaires assessing cardiopulmonary and mental health are used.

Study to Evaluate CD8 PET Imaging as a Marker of Immune Response to Stereotactic Body Radiation Therapy (ELIXR)

"This phase I trial investigates the effect of radiation therapy on the immune system, specifically CD8 positive (+) T cells, in lymphoma patients receiving bridging radiation therapy before CAR T-cell infusion, and metastatic patients with solid tumor malignancies receiving SBRT. CD8+ T cells are mainly found in lymph tissue and play a significant role in anti-tumor immunity. These cells can infiltrate tumor cells and kill them. Radiation therapy may recruit CD8 T cells and this recruitment may help with tumor control. Diagnostic procedures, such as zirconium Zr 89-Df-crefmirlimab positron emission tomography (PET), may be a less invasive way to check and monitor for CD8+ T cells before and after radiation therapy."

Pharmacokinetic Study of Venetoclax Tablets Crushed and Dissolved Into a Solution

The use of venetoclax-based therapies for pediatric patients with relapsed or refractory malignancies is increasingly common outside of the clinical trial setting. For patients who cannot swallow tablets, it is common to crush the tablets and dissolve them in liquid to create a solution. However, no PK data exists in adults or children using crushed tablets dissolved in liquid in this manner, and as a result, the venetoclax exposure with this solution is unknown. Primary Objectives • To determine the pharmacokinetics of venetoclax when commercially available tablets are crushed and dissolved into a solution Secondary Objectives * To evaluate the safety of crushed venetoclax tablets administered as an oral solution * To determine the pharmacokinetics of venetoclax solution in patients receiving concomitant strong and moderate CYP3A inhibitors * To determine potential pharmacokinetic differences based on route of venetoclax solution administration (ie. PO vs NG tube vs G-tube) * To determine the concentration of venetoclax in cerebral spinal fluid when administered as an oral solution

REmote iSchemic condItioning in Lymphoma PatIents REceiving ANthraCyclinEs

Multinational, prospective, proof of concept phase II, double-blinded, sham-controlled, randomized clinical trial (RCT) to evaluate the efficacy and safety of Remote Ischaemic PreConditioning (RIPC) in Lymphoma patients receiving anthracyclines.

Non-covalent BTK Inhibitor Nemtabrutinib in Combination With the CD20 Monoclonal Antibody Rituximab for the Treatment of Marginal Zone Lymphoma

This phase II trial tests the effect of nemtabrutinib in combination with rituximab in treating patients with marginal zone lymphoma. Nemtabrutinib, a non-covalent Bruton's tyrosine kinase (BTK) inhibitor, may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Giving nemtabrutinib in combination with rituximab may be safe, tolerable and/or effective in treating patients with marginal zone lymphoma.

Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (ViPOR) in Relapsed/Refractory B-cell Lymphoma

Background: B-cell lymphoma is a cancer of white blood cells found in the lymph nodes. It affects the system that fights infections and disease. Researchers want to learn how certain drugs work together to treat B-cell lymphomas. The drugs are venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide (ViPOR). Objective: To study the safety of ViPOR for people with B-cell lymphoma. Eligibility: People ages 18 and older with B-cell lymphoma whose cancer has returned or not improved after treatment Design: Participants will be screened with: * Medical history * Physical exam * Blood, urine, and heart tests * Tissue sample from previous procedure * Imaging scans * Registration for counseling on the risks of lenalidomide. They must get counseling at least every 28 days. Participants will have a bone marrow aspiration before treatment. Participants may have tumor samples taken. Participants will get ViPOR in 21-day cycles. For up to 6 cycles: * Participants will get one drug by IV on days 1 and 2. * Participants will take the other four drugs by mouth on most days. After their first dose of venetoclax, they will stay in the clinic for at least 8 hours and return the next day for monitoring. They may be admitted for more drugs or monitoring. Participants will keep a drug diary. Participants will have a physical exam and blood and urine tests at least once per cycle. They will have scans 4 times over 6 cycles. Participants will have a visit about 1 month after their last dose of study drug. They will then have visits every few months for 3 years, and once a year for years 4 and 5. Visits include a physical exam, blood tests, and scans....

Leukapheresis for CAR or Adoptive Cell Therapy Manufacturing

Background: Leukapheresis is a procedure to separate and collect white blood cells. It is the first step in a treatment called CAR (chimeric antigen receptor) T-cell therapy. CAR-T therapy may be offered to people when their cancer comes back. The collected T-cells are used to make a special version of T-cells called CARs. Researchers want to collect these cells from people who may become eligible for a CAR T-cell study in the future. Objective: To identify people who have a high likelihood to benefit from CAR T-cell therapy early in their disease course and collect and store a T-cell product. Eligibility: People ages 3-65 with a form of leukemia or lymphoma that has not been cured by standard therapy Design: Participants will be screened with medical history, physical exam, and blood and urine tests. Review of existing MRI, x-ray, pathology specimens/reports or CT images may be done. On this study, participants will have leukapheresis. A needle will be placed into the arm. Blood will be collected and go through a machine. White blood cells will be taken out by the machine. The plasma and red cells will be returned to the participant through a second needle in the other arm. The procedure will take 4-6 hours. Some participants may have a central line (catheter) inserted which is needed to do the leukapheresis procedure, instead of the needles in the arms-especially if they are smaller. For a central line placement, a long thin tube is inserted through a small incision into the main blood vessel leading into the heart that would allow access to the blood to do the leukapheresis procedure. Participants cells will be processed and frozen for future use in a CAR T-cell therapy study.

Tissue, Blood, and Body Fluid Sample Collection From Patients With Hematologic Cancer

RATIONALE: Collecting and storing samples of tissue, blood, and body fluid from patients with cancer to study in the laboratory may help the study of cancer in the future. PURPOSE: This research study is collecting and storing blood and tissue samples from patients being evaluated for hematologic cancer.

HEME Home Transfusion Program

This research study is evaluating whether a new care delivery program that provides access to home blood transfusions in hospice (i.e, HEME-Hospice) compared to regular standard of care improves quality of life, mood, and end-of-life health care utilization for patients with hematologic malignancies.

A Study to Evaluate the Safety and Pharmacokinetics of Eflapegrastim in Pediatric Participants With Solid Tumors or Lymphomas and Treated With Myelosuppressive Chemotherapy

The purpose of this study is to evaluate the safety and pharmacokinetics of eflapegrastim in pediatric participants with solid tumors or lymphoma and treated with myelosuppressive chemotherapy.

Dose Escalation and Dose Expansion Study of MDX2003 in Patients With Different Types of Lymphoma

This study is designed to characterize the safety, tolerability, and anti-tumor activity of MDX2003 in patients with different types of lymphoma

Neuromodulation of Cardiovascular Risks Associated With Cardiotoxic Chemotherapy

This study is to determine if low level vagus nerve stimulation will lead to improvement in heart function, heart rate variation, and in the levels of certain chemical markers of inflammation in study participants' blood.

Assessment of Cognitive Function in Breast Cancer and Lymphoma Patients Receiving Chemotherapy

Cognitive impairments in cancer patients represent an important clinical problem. Studies to date estimating prevalence of difficulties in memory, executive function, and attention deficits have been limited by small sample sizes and many have lacked healthy control groups. More information is needed on promising biomarkers and allelic variants that may help to determine the etiology of impairment, identify those most vulnerable to impairment, and develop interventions for these difficulties. This is a longitudinal observational study of cognitive function in breast cancer and lymphoma patients receiving chemotherapy to better understand the prevalence of cognitive difficulties (i.e., problems with memory, executive function, and attention) in these populations.

Phase I Trial to Determine the Dose and Evaluate the PK and Safety of Lutetium Lu 177 Edotreotide Therapy in Pediatric Participants With SSTR-positive Tumors

The purpose of the study is to determine the appropriate pediatric dosage and evaluate the pharmacokinetics (PK) and safety of Lutetium Lu 177 Edotreotide Targeted Radiopharmaceutical Therapy (RPT) as a monotherapy or following standard of care (SoC) in participants ≥2 to \<18 years of age with somatostatin receptor (SSTR)-positive tumors.

A Resilience-Based Approach to Improve Long-term Quality of Life in Post-treatment Lymphoma Survivorship

The goal of this trial is to learn if a resilience intervention can lead to improvements in lymphoma survivors' quality of life.

Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)

This phase II MATCH screening and multi-sub-trial studies how well treatment that is directed by genetic testing works in patients with solid tumors, lymphomas, or multiple myelomas that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and does not respond to treatment (refractory). Patients must have progressed following at least one line of standard treatment or for which no agreed upon treatment approach exists. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with genetic abnormalities (such as mutations, amplifications, or translocations) may benefit more from treatment which targets their tumor's particular genetic abnormality. Identifying these genetic abnormalities first may help doctors plan better treatment for patients with solid tumors, lymphomas, or multiple myeloma.

Pembrolizumab + Chemotherapy in Newly Diagnosed PCNSL

This research study is studying if the investigational drug, Pembrolizumab, in combination with chemotherapy helps primary central nervous system lymphoma with acceptable side effects. This research study involves a combination of the below drugs: * Pembrolizumab (a type of monoclonal antibody) * Methotrexate (a type of anti-metabolite) * Temozolomide (a type of alkylating agent) * Rituximab (a type of antibody)

Study of Ruxolitinib in Relapsed or Refractory T or NK Cell Lymphoma

The purpose of this study is to test any good and bad effects of the study drug called ruxolitinib. Ruxolitinib works by blocking a protein called JAK. JAK works along with another protein called STAT and is important for survival of many T or NK-cell lymphomas. By blocking JAK, ruxolitinib may cause T or NK-cell lymphomas to shrink.