Clinical Research Directory

A Phase I Study of Mozobil in the Treatment of Patients With WHIMS

Background: * WHIMS (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis Syndrome) is caused by various genetic changes that increase the activity of the chemokine receptor, CXCR4. Excessive function of this receptor causes mature neutrophils (part of the white blood cells) to be retained within the bone marrow rather than being released to the blood and is one of the causes of severe inherited neutropenia (low white blood counts). In neutropenia, the body is less able to fight off infection. Patients with WHIMS usually are at risk for skin, soft tissue, sinus, and lung infections, which can result in loss of hearing, teeth, and lung function. * Current treatment for WHIMS consists of regular injections of a white blood cell growth stimulating medication called granulocyte colony stimulating factor (G-CSF), and supplemental immunoglobulin (antibody). These therapies are expensive, nonspecific, have significant side effects and toxicities, and do not fully correct all problems, especially warts and cancers related to human papillomavirus (HPV). * A drug called Mozobil has been approved for use in combination with G-CSF to increase the number of stem cells that can be collected prior to bone marrow transplantation. Mozobil may offer a specific and well-tolerated new treatment for WHIMS and other syndromes characterized by neutropenia. Objectives: * To evaluate whether Mozobil is safe and effective to treat neutropenia (low white blood cell count) in patients with WHIMS. * To determine an appropriate treatment dose of Mozobil, within currently approved dosage levels. Eligibility: \- Individuals between 18 and 75 years of age who have been diagnosed with WHIMS and have a history of severe infections. Design: * Potential participants will undergo a screening with a medical history, physical examination, questionnaire, heart and lung function scans, and blood and urine samples. Tests will also be done for hepatitis B and C virus, and human immunodeficiency virus (HIV) that causes acquired immunodeficiency syndrome (AIDS), as well as to check neutrophil function. * Patients who are being treated with G-CSF will stop injections for 2 days before being admitted to the National Institutes of Health (NIH) Clinical Center. * Patients may participate in a Dose Escalation study and receive increasing doses of Mozobil over 5 days of treatment until their white blood cell count improves sufficiently or the maximum approved dose is reached. Blood samples will be taken regularly throughout the treatment process. Patients will then receive an additional dose of Mozobil at the maximum approved dose or the dose sufficient to cause improvement, before restarting the G-CSF injections. * Patients may also participate in a long-term Chronic Dosing study and receive Mozobil once or twice a day for up to a maximum of 60 months.

Luspatercept for Clonal Cytopenias of Uncertain Significance

The purpose of this clinical trial is to test how well the drug luspatercept works in improving low blood cell counts in people with clonal cytopenias of uncertain significance (CCUS). The main questions the study seeks to answer include: * How many patients experience improvements in their low blood counts (red cells, platelets, or white cells) within 24 weeks, based on specific criteria for blood conditions like myelodysplastic syndromes (MDS)? * How long these improvements last before the condition worsens or changes. * The percentage of participants showing improvements at 12, 24, and 48 weeks. * How long it takes for the condition to progress to more severe diseases like myeloid disorders. * How long red blood cell responses last and how quickly these responses are seen. * The average change in hemoglobin levels over 24 weeks. * How many patients need blood transfusions during the study and how soon transfusions are required. * Changes in participants' well-being and energy levels based on a standardized questionnaire. * Monitoring for any side effects, including progression to MDS or leukemia, heart-related issues, or sudden increases in hemoglobin. Participants will: * Receive luspatercept as an injection every three weeks. * Visit the clinic every three weeks for treatment and monitoring.

Predictive Score in Patients With Hematological Malignancies Colonized by Multidrug-resistant Enterobacteriaceae

The goals of this observational study are to identify risk factors for ESBL-producing Enterobacterales and carbapenemase-producing Enterobacterales (CPE) colonization in oncohematological patients with severe neutropenia, and to develop and validate a predictive model of infection caused by ESBL-producing Enterobacterales and CPE in patients previously colonized by the same bacteria. The main questions the study aims to answer are: * What are the risk factors for ESBL-producing Enterobacterales and CPE colonization in patients with severe neutropenia? * Can a predictive model be developed to accurately predict infections in the colonized patients? Study Design \& Participants: Participants will be screened after receiving neutropenia-inducing treatment (e.g., chemotherapy, chimeric antigen receptor T-cell (CAR-T) therapy, or others). A baseline rectal swab will be collected to assess initial colonization status, followed by weekly swabs throughout the duration of neutropenia. Patients will be followed for 90 days from initial screening, during which the study team will record any infections, with an additional 30-day follow-up period. All hospitalization data will be recorded.

A Study of Mavorixafor in Participants With Congenital and Acquired Primary Autoimmune and Idiopathic Chronic Neutropenic Disorders Who Are Experiencing Recurrent and/or Serious Infections

The purpose of this study is to demonstrate the efficacy and evaluate the safety and tolerability of mavorixafor in participants with congenital or acquired primary autoimmune and idiopathic chronic neutropenic disorders who are experiencing recurrent and/or serious infections as assessed by demonstrating its clinical benefit and increasing levels of circulating neutrophils.

Real-world Study on the Prevention of Neutropenia After Tumor Treatment With Mecapegfilgrastim Injection

This study is a multicenter, observational real-world study, aiming to observe and evaluate the efficacy and safety of prophylactic application of Mecapegfilgrastim Injection in tumor patients after radiotherapy/chemotherapy/immunotherapy in the real world to prevent neutropenia.The subjects who met the inclusion criteria of the protocol were defined as those who needed radiotherapy/chemotherapy/immunotherapy after being diagnosed with solid malignant tumors. The researchers believed that the subjects needed to use Mecapegfilgrastim Injection for primary/secondary prevention after receiving tumor treatment.

Comparing Diosmin-Hesperidin and Loratadine to Prevent Bone Pain From G-CSF in Patients With Blood Cancers

This is a comparative interventional study to determine the best way to prevent G-CSF induced bone pain in patients with hematological malignancies (blood cancers). G-CSF (Granulocyte Colony-Stimulating Factor) is a drug commonly used in these patients to boost white blood cell production, but it frequently causes severe bone pain. The study is comparing two oral medications for their effectiveness as a preventive treatment: * Diosmin-Hesperidin (a flavonoid supplement). * Loratadine (a common anti-allergy medication). The core question the study is trying to answer is: * Is diosmin-hesperidin effective in preventing G-CSF-induced bone pain compared to loratadine? * Does the combination of diosmin-hesperidin and loratadine offer better pain prevention than either drug alone?

Serial Blood Count Study

The objective of the Serial Blood Count Study is to determine the utility of home monitoring of white blood cell (WBC) and absolute neutrophil counts (ANC) to diagnose cyclic neutropenia and distinguish between cyclic and severe congenital neutropenia (SCN). A new home monitoring device called Athelas One was granted an FDA 510K Class 2 clearance for evaluation of white blood count (WBC) and absolute neutrophil count (ANC). The investigators believe this device provides a unique and extremely valuable opportunity to for diagnosis of these diseases.

Prospective Study Evaluate the Timing of Empirical Treatment for Carbapenem-resistant Bacterials (CROEAT Study)

In this study, we will evaluate the feasibility and clinical outcomes of risk adaptive empirical therapy to cover carbapenem resistance gram negative bacteria (CRO) in patients with hematological malignancies colonized with CRO. Patients assessed by the clinician as being at high risk for CRO infection and requiring intravenous antibiotics covering CRO must meet the following conditions: 1. Positive active screening for CRO or past CRO infection or local prevalence of CRO (e.g.,CRO detection rate\>20% among recently hospitalized patients); 2. Presence of fever or other possible signs and symptoms of infection; 3. Neutropenia(ANC\<0.1×10\^9/L)expected to last for ≥7 days,and having any of the following: * Gastrointestinal mucositis/peri-anal infection/intestinal obstruction; * Shock or severe sepsis; * Respiratory failure:deoxygenated PaO2\<60 mmHg or requiring mechanical ventilation; * Disseminated intravascular coagulation; * Altered mental status or psychiatric abnormalities; * Congestive heart failure requiring treatment; * Arrhythmia requiring treatment; * Recurrence of fever shortly after cessation of or during empirical treatment with carbapenems (≤7 days). The endpoints of study include incidence of blood-stream infection by CRO, incidence of all causes mortality, incidences of clinical and microbiology response.

A Study on the Use of Sulpegfilgrastim to Prevent the Incidence of Neutropenia With Infection in Newly Diagnosed Non-transplant Multiple Myeloma Patients

The goal of this study is to observe and evaluate the incidence of infection in newly diagnosed, non-transplanted multiple myeloma patients receiving prophylactic treatment with sulpegfilgrastim (a pegylated recombinant human granulocyte colony-stimulating factor).

Breath Analysis for the Detection of Invasive Fungal Infections

Patients with leukemia and concomitant neutropenia are at high risk of developing invasive fungal infections (IFI) that are associated with high morbidity and mortality. As these patients typically have severe thrombocytopenia, direct diagnostic sampling with invasive procedures is often not possible due to the high peri-interventional risk. Therefore, the presumptive diagnosis of IFI is primarily based on compatible lung findings on computed tomography and serologic detection of fungal cell wall components, which, however, have limited sensitivity and specificity. With the present study, the investigators aim to determine a set of specific volatile biomarkers in leukemia patients with proven or probable IFI using secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS).

Letermovir for Secondary Prophylaxis in Solid Organ Transplant Recipients

This is a research study to test the tolerability and clinical effectiveness of the study drug, Letermovir (LET), when used as secondary prophylaxis following treatment of Cytomegalovirus (CMV) infection and disease in a solid organ transplant recipient. This study is an open label trial in which Letermovir will be prescribed to prevent the recurrence of CMV infection and disease in a solid organ transplant recipient following treatment of CMV infection or disease.

The Prevalence and Impacts of Nudix Hydrolase 15 (NUDT15) Gene Variants in Taiwanese Inflammatory Bowel Disease

The study will include participants who were diagnosed with inflammatory disease and followed up at National Taiwan University Children's Hospital. The investigators will check the NUDT15 gene test, if the participant agrees to do an additional blood test. The result of the gene test will be analyzed and compared with other clinical data.

UCMSC-Exo for Chemotherapy-induced Myelosuppression in Acute Myeloid Leukemia

The purpose of the study is to explore the safety and efficacy of UCMSC-Exo in consolidation chemotherapy-induced myelosuppression in patients with acute myeloid leukemia after achieving complete remission.

Continuous Versus Bolus Administration of G-CSF in Children With Cancer

The investigators hypothesized that in terms of granulocyte colony-stimulating factor (G-CSF) administration, the route of continuous infusion would lead to a faster neutrophil recovery compared to that of bolus administration

Effects of Levetiracetam Monotherapy on Various Hematological Parameters in Adult Patients Suffering of Epilepsy

Low therapeutic index of established antiepileptic drugs (AEDs) coupled with better understanding of the pathophysiology of seizure has encouraged the development of several novel AEDs. The conventional antiepileptics like phenytoin, phenobarbitone, valproate and carbamazepine and newer antiepileptics like levetiracetam. are used for epilepsy. AEDs induce potentially toxic effects over a period of time which remains undetermined over very long time. Earlier studies in this regard, states uneven results about hematological (Hb%, blood cell count etc.) toxicity of AEDs.

Ceftolozane/Tazobactam vs. Piperacillin/Tazobactam for the Treatment of Bacteremia in Hemato-oncological Patients

Patients with hematological malignancies receive highly myelotoxic chemotherapy regimens that cause periods of severe myelosuppression, which places them at high risk of developing bacteremia. At a global level, a very significant increase in multidrug-resistant (MDR) Gram-negative microorganisms, particularly Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBL) and MDR P.aeruginosa, have been described during the last decade. Among the strategies to reduce bacterial resistance, ceftolozane/tazobactam (C/T) as a "carbapenem-sparing" antibiotic has been proposed. C/T has broad-spectrum activity since it has action against ESBL-producing Enterobacteriaceae and MDR P. aeruginosa. Studies carried out in the real world using this antibiotic in patients with hematological malignancies have demonstrated clinical success in reports and case series, considered a therapeutic option in patients with Enterobacteriaceae and P. aeruginosa infections, particularly in MDR pathogens. At the National Cancer Institute (in Spanish, Instituto Nacional de Cancerologia), Gram-negative bacilli have been identified for more than 20 years as the pathogens most frequently associated with bacteremia. Escherichia coli occupies the first place in 25% (41% ESBL), followed by Klebsiella spp. in 5.6% (11.2% ESBL) and P. aeruginosa in 5.6% (11.2% MDR). The protocol for approaching and treating hematological malignancy patients with severe neutropenia and fever is to initiate an antimicrobial regimen with piperacillin/tazobactam (P/T). In patients who persist with fever after 48 to 72 hours of starting antibiotics, who present with clinical deterioration, or in whom P/T-resistant bacteria are identified, this is escalated to carbapenem. Therefore, it is proposed to compare the clinical and microbiological response in patients with hematological malignancies who present with severe neutropenia and fever and who present clinical data of bacteremia, with empirical treatment with C/T vs. P/T, trying to reduce the use of carbapenems in this group of patients.

A Comparator Study of a Tasso Device Blood Sample to Traditional Venous Blood Sample for CBC

This study will evaluate the feasibility of using capillary blood samples collected with the Tasso device for analysis of CBC in diseased patients with leukemia, lymphoma, and/or other blood cell disorders. This investigation will include a minimum of 40 sample sets from unique patients.

Prospective Evaluation of Xerava Prophylaxis in Hematological Malignancy Patients With Prolonged Neutropenia

Antibacterial prophylaxis is recommended in patients at high risk of infection, specifically patients undergoing acute leukemia induction therapy or hematopoietic stem cell transplant (HSCT) who are expected to have profound neutropenia (ANC\<100 neutrophils/milliliter) for more than seven days. Xerava™ (eravacycline) has a broad spectrum of activity including many multi-drug resistant strains of bacteria. It is not an agent used for treatment of febrile neutropenia, making eravacycline a very attractive alternative to consider in this prophylactic setting. Eravacycline has activity against MRSA, VRE, and Clostridioides difficile, all of which are common problems in this patient population. It also covers the majority of enteric gram-negative pathogens while also producing satisfactory tissue penetration and adequate plasma concentrations, which has classically been a concern with prior agents. Eravacycline has activity against coagulase-negative staphylococcus, which is a common catheter-related infection in leukemia and HSCT patients. The primary objective will be report the incidence of breakthrough infections during eravacycline prophylaxis for hematologic malignancy patients with prolonged neutropenia.

Cologne Cohort of Neutropenic Patients (CoCoNut)

The Cologne Cohort of Neutropenic Patients (CoCoNut) is a non-interventional cohort study assessing risk factors, interventions, and outcome of immunosuppressed patients with or without opportunistic infections.