StudyFinder
Search Results Within Category "Infectious Disease/Immune System"
31 Study Matches
18F-Fibroblast Activation Protein Inhibitor (18F-FAPI-74) in Tuberculosis Patients
Kerrigan Perkins - kerrigan.perkins@cchmc.org
ALL
18 years and over
NCT07077213
Inclusion criteria: Patients may be enrolled into this protocol only if all the following inclusion criteria are met:
* Greater than or equal to 18 years of age
* Culture confirmation of M. tuberculosis, or sputum positive by molecular testing (GeneXpert).
* Imaging evidence of suspected M. tuberculosis disease involving lung, and possible additional other sites of involvement. Modalities can include any imaging modality such as chest x-ray, CT, ultrasound, MRI, 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (\[18F\]FDG) PET/CT, bone scan.
* TB treatment initiation within 6-weeks by the time of the study PET/CT scan OR within 6-weeks after receiving 6-months of TB treatments. Using this approach, we will be able to assess fibrosis in TB patients at treatment initiation as well as having received TB treatments. The same patient may be re-consented for a scan at the later time-point.
* Subject is willing to give written informed consent.
* Subject is willing and able to comply with the protocol for the duration of the study including undergoing scheduled visits and study procedures.
* Screening clinical laboratory values must be within normal limits or judged not clinically significant by the investigator.
* Women of child-bearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours prior to the radiotracer administration.
* Patients or their legal representatives must have the ability to read, understand and provide written informed consent for the initiation of any study related procedures.
Exclusion criteria: Patients will be excluded from enrollment if any of the following apply:
* Inadequate venous access (two antecubital or equivalent venous access sites are required for study drug injection and pharmacokinetics (PK) blood sampling, respectively)
* Lactating females
* Administered a radioisotope within 5 physical half-lives as part of a research study prior to study enrollment.
* Determined to have prior (external) radiation exposure from research studies which will exceed Radioactive Drug Research Committee (RDRC) annual radiation exposure limit of 5 rems.
* Any medical condition that in the judgment of the investigator would make the patient inappropriate for entry into this study.
COMBINATION_PRODUCT: 18F-FAPI-74
Tuberculosis, Pulmonary
Comparison of Uncomplicated Candidemia Therapy Duration in Children (COUNT)
Caitlin Caitlin Brammer - Caitlin.Brammer@cchmc.org
ALL
4 month(s) and over
NA
NCT05763251
Inclusion Criteria:
• Age \> 120 days at the time of the first negative blood culture at any participating site;
• Candidemia with at least one positive blood culture for any Candida spp;
• Receiving/received an echinocandin (caspofungin, micafungin, anidulafungin, or rezafungin) as primary antifungal therapy for candidemia for at least 2 days from day of first negative culture with continuation of uninterrupted systemic antifungal therapy at the time of enrollment);
• Sustained clearance of Candida spp. defined as negative blood culture(s) obtained after onset of candidemia and before day of randomization;
• Partial or complete clinical response, as defined by published guidelines (Table 5), on or before day of randomization;
• Between the onset of qualifying candidemia and randomization, no suspicion of disseminated candidiasis by patient's clinical team or, if deemed clinically necessary, documented negative radiological imaging such as an abdominal ultrasound or abdominal CT scan.
Exclusion Criteria:
• Already receiving antifungal therapy for a previously diagnosed systemic invasive fungal disease;
• Neutropenic (absolute neutrophil count \< 500 cells/µl) at the time of enrollment or anticipated to be neutropenic in the week following randomization;
• Have an underlying condition that requires them to be on antifungal prophylaxis when not receiving directed therapy for an invasive fungal disease;
• Previous enrollment in this trial;
• Females of childbearing age with a current pregnancy diagnosis or without a negative pregnancy test for their current admission;
• A documented DNR order;
• Have an implantable cardiac device (e.g., ventricular assist device, pacemaker)
OTHER: therapy duration
Invasive Candidiasis
A Study of BLB-201 RSV Vaccine in Infants and Children
Jamie Kidd - jamie.kidd@cchmc.org
ALL
6 months to 5 years old
PHASE1
NCT05655182
Inclusion criteria for sero+ children 18 to 59 months of age enrolled in Groups 1 and 2:
Healthy children at least 18 months but less than 60 months of age whose legally-acceptable representative (LAR) understands and signs the trial informed consent and agrees to vaccine administration following a detailed explanation of the trial.
Determined by medical history, targeted physical exam, and clinical judgement of the investigator to be in a good state of health. Screening laboratory values slightly outside lab normal ranges may be acceptable if the site investigator determines that they are not clinically significant. Permitted concomitant medications include nutritional supplements, medications for gastroesophageal reflux, eye drops, and topical medications, including topical steroids, topical antibiotics, and topical antifungal agents.
Sero+ for RSV as defined by serum RSV antibody titer assay
Participant is expected to be available for the duration of the trial.
The LAR confirms that the subject has received routine immunizations appropriate for age based on the current Advisory Committee on Immunization Practices (ACIP) Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger.
Growing normally for age as demonstrated on a World Health Organization (WHO) growth chart, AND has a current height and weight above the 3rd percentile for age.
Inclusion criteria for sero+ or sero- infants and children 8 to 24 months of age enrolled in Groups 3 through 6:
Healthy children at least 8 months but less than 25 months of age whose LAR understands and signs the trial informed consent and agrees to vaccine administration following a detailed explanation of the trial.
Determined by medical history, targeted physical exam, and clinical judgement of the investigator to be in a good state of health. Screening laboratory values slightly outside lab normal ranges may be acceptable if the site investigator determines that they are not clinically significant. Permitted concomitant medications include nutritional supplements, medications for gastroesophageal reflux, eye drops, and topical medications, including topical steroids, topical antibiotics, and topical antifungal agents.
Sero- OR sero+ for RSV antibody, defined by serum RSV antibody titer assay not more than 30 days prior to vaccination.
Participant is expected to be available for the duration of the trial.
The LAR confirms that subject has received routine immunizations appropriate for age based on the current Advisory Committee on Immunization Practices (ACIP) Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger.
Growing normally for age as demonstrated on a World Health Organization (WHO) growth chart, AND
If \<1 year of age: has a current height and weight above the 5th percentile for age.
If ≥1 year of age: has a current height and weight above the 3rd percentile for age.
Subject Exclusion Criteria
\<8 months of age and \>60 months of age at the time of planned vaccine inoculation.
Born at less than 34 weeks gestation for subjects ≥ 1 year of age at enrollment
Born at less than 37 weeks gestation, and at the date of inoculation less than 1 year of age.
Maternal history of a positive HIV test before or during pregnancy.
Maternal history of illicit drug abuse or alcohol abuse.
Evidence of chronic disease except for chronic diseases that are mild, stable and not immune compromising or require recent change (\< 60 days) in management (e.g., mild stable eczema, mild allergic rhinitis)
Clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality as determined by medical history or physical exam. Abnormal pulse oximetry testing during screening for undetected critical congenital heart disease or concern for such by medical history or physical exam.
Acute or chronic medical condition or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgement, make the participant inappropriate for the study.
History of severe infection (e.g., requiring hospitalization).
Known or suspected impairment of immunological functions, bone marrow/solid organ transplant recipients.
Receiving immunosuppressive therapy including systemic corticosteroids.
Major congenital malformations, including congenital cleft palate or cytogenetic abnormalities.
Suspected or documented developmental disorder, delay, or other developmental problem.
Cardiac abnormality requiring treatment. Participants with clinically insignificant cardiac abnormalities (e.g., clinically insignificant patent foramen ovale) requiring no treatment may be enrolled.
Lung disease or reactive airway disease.
History of wheezing episode/s or receipt of bronchodilator therapy
Previous receipt of supplemental oxygen therapy in a home setting.
History of severe RSV infection or severe respiratory virus infection (e.g., requiring hospitalization).
Previous immunization with an investigational RSV vaccine.
Previous or planned administration of any anti-RSV antibody product within 6 months of receipt of study vaccine.
Previous receipt of immunoglobulin or any other antibody products within the past 6 months.
Previous receipt of any blood products within the past 6 months.
Previous anaphylactic reaction.
Previous serious vaccine-associated adverse reaction or one that was Grade 3 or above.
Known hypersensitivity to any study vaccine product component.
Household contact with any of the following groups of individuals for the period up to 28 days after vaccination (including after each dose for cohorts receiving two doses of vaccine):
Member of a household that contains an infant who is less than 6 months of age at the date of inoculation through the 28th day after inoculation. In groups assigned to two doses of vaccine, to include date of inoculation through the 28th day after the second inoculation.
Pregnant woman.
Persons with hospitalization for asthma or other chronic respiratory disease in the past 5 years.
Member of a household that, at the date of inoculation through the 28th day after inoculation (including second dose if scheduled), contains an immunocompromised individual including but not limited to:
A person who is HIV-infected.
A person who has cancer and has received chemotherapy within the 12 months prior to enrollment.
A person with a solid organ or bone marrow transplant.
A person currently receiving immunosuppressive agents.
Attends a daycare facility that does not separate children by age and contains an infant
\<6 months of age at the date of inoculation through the 28th day after inoculation.
Neurological and neurodevelopmental conditions (e.g., cerebral palsy, epilepsy, stroke, seizures).
History of postinfectious or postvaccine neurological sequelae.
Autoimmune, inflammatory, vascular, or rheumatic disease.
Household contact of another child enrolled into the trial.
Inadequate venous access for repeated phlebotomy.
Subject's LAR/s who, in the opinion of the site investigator, are not suitable participants for the study, for any reason not previously delineated, including subjects with any condition that would in the opinion of the site investigator place the subject at unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.
Subjects testing positive for infection with RSV, Influenza, or SARS-CoV-2 in the 3 months prior to enrollment.
Planned receipt of any of the following prior to planned trial vaccine receipt (Day 1 and Day 57 for group receiving 2 doses of vaccine):
Inactivated influenza vaccine within 14 days prior, or
Any other inactivated vaccine or live-attenuated rotavirus vaccine within the 14 days prior, or
Any live vaccine, other than rotavirus vaccine, within the 28 days prior, or
Another investigational vaccine or investigational drug within 28 days prior.
Salicylate (aspirin) or salicylate-containing products within 28 days prior.
Planned receipt of any of the following after planned trial vaccine receipt (Day 1 and Day 57 for groups receiving 2 doses of vaccine):
Inactivated vaccine or live-attenuated rotavirus vaccine within the 14 days after, or
Any live vaccine other than rotavirus in the 28 days after, or
Another investigational vaccine or investigational drug in the 56 days after.
Planned receipt of any of the following medications within 7 days of trial enrollment and 7 days after trial vaccine (Day 1 and also Day 57 for groups receiving 2 doses of vaccine):
Systemic antibacterial, antiviral, antifungal, anti-parasitic, or antituberculous agents, whether for treatment or prophylaxis, or systemic or nasal steroid therapy for acute illness.
Any other intranasal medications, or
Other prescription medications except permitted concomitant medications. Permitted concomitant medications (prescription or non-prescription) include nutritional supplements, medications for gastroesophageal reflux, eye drops, and topical medications, including (but not limited to) cutaneous (topical) steroids, topical antibiotics, and topical antifungal agents.
History of bleeding disorder or significant problem with bleeding
American Indian or Alaska Native Infants/Children (high risk for severe RSV infection) AND eligible to receive nirsevimab
Temporary exclusion criteria for sero+ children, sero- children, and infants:
The following are temporary or self-limiting conditions, and once resolved, the subject may be enrolled, if otherwise eligible. If the period of temporary exclusion is greater than 30 days, sero- children will need to be rescreened for levels of RSV neutralizing antibody.
Any of the following events at the time of enrollment:
Fever (temperature of ≥100.4°F per site standard based on age; e.g., oral for older children, rectal for infants, axillary screening), or
Upper respiratory signs or symptoms (rhinorrhea, cough, or pharyngitis) or
Nasal congestion significant enough to interfere with successful vaccination.
Otitis media.
Contact with a person diagnosed with RSV, Influenza, coronavirus disease-2 (COVID- 19) or other viral respiratory illnesses within the preceding 10 days.
BIOLOGICAL: PIV5-vectored RSV Vaccine (BLB-201) Low Dose, BIOLOGICAL: PIV5-vectored RSV Vaccine (BLB-201) High Dose, DRUG: Placebo
Respiratory Syncytial Virus Infections
Human respiratory syncytial virus (RSV), Lower respiratory tract infection (LRTI)
Third Party Viral Specific T-cells (VSTs)
Jamie Wilhelm - Jamie.Wilhelm@cchmc.org
ALL
0 month(s) and over
PHASE2
NCT02532452
Inclusion Criteria:
* Immunocompromised patient with evidence of viral infection or reactivation
* Age \>1 day
* Recipients who have had a stem cell transplant must be at least 21 days after stem cell infusion
* Clinical status must allow tapering of steroids to \< 0.5mg/kg prednisone or other steroid equivalent
* Must be able to receive CTL infusion in Cincinnati
* Informed consent obtained by PI or sub-investigator either in person or by phone
Exclusion Criteria:
* Active acute GVHD grades II-IV
* Uncontrolled bacterial or fungal infection
* Uncontrolled relapse of malignancy requiring treatment with chemotherapy
* Infusion of ATG or alemtuzumab within 2 weeks of VST infusion
* Biopsy confirmed acute rejection of solid organ transplant OR empiric treatment of suspected but not confirmed acute rejection of solid organ transplant within the last 30 days BIOLOGICAL: Viral Specific VST Infusion
Viral Infection, Viral Reactivation, Infection in an Immunocompromised Host
Epstein-Barr Virus (EBV), Adenovirus (ADV), Cytomegalovirus (CMV), T-Cells, Donor, BK virus (BKV)
A Clinical Study of Letermovir (MK-8228) in Children and Adolescents Who Receive a Kidney Transplant (KT) (MK-8228-077)
Caitlin Brammer - caitlin.brammer@cchmc.org
ALL
Up to 17 years old
PHASE1
NCT07199465
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
* Is a recipient of a primary or secondary allograft kidney
* Is at least 4 weeks posttransplant and not more than 52 weeks posttransplant at the time of enrollment (Day 1) and is being managed per local standard of care
* Has stable kidney function posttransplant
* Has undetectable CMV deoxyribonucleic acid (DNA) from a plasma or whole blood sample collected within 14 days prior to enrollment
* Must be able to take (as assessed by the investigator) letermovir tablets or oral pellets by mouth, or via gastrostomy or nasogastric tube (oral pellets only)
* Does not have a condition that may interfere with the absorption of oral medication (e.g., vomiting, diarrhea, or a malabsorptive condition) from the day of enrollment (Day 1) until the intensive pharmacokinetics (IPK) sampling is completed
* Weighs ≥2.5 and \<40 kg at enrollment (Day 1)
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Has CMV disease or suspected CMV disease between screening and enrollment
* Is on dialysis or plasmapheresis at the time of enrollment
* Has evidence of CMV viremia at any time from screening until the time of enrollment
* Has Child-Pugh B or C hepatic insufficiency within 14 days before enrollment
* Is a multi-organ transplant recipient (e.g., kidney-pancreas)
* Has any uncontrolled infection on the day of enrollment
* Requires mechanical ventilation, or is hemodynamically unstable, at the time of enrollment
* Has received or is receiving protocol-specified prohibited medications DRUG: Letermovir
Cytomegalovirus Prophylaxis
Safety Study of Unlicensed IND Cord Blood Units Manufactured by the National Cord Blood Program for Unrelated Transplantation
Stephanie Edwards - stephanieL.edwards@cchmc.org
ALL
PHASE2
NCT01656603
Inclusion Criteria:
• Diagnosis: Patients with disorders affecting the hematopoietic system that are inherited, acquired, or result from myeloablative treatment.
• Patients: Patients of any age and either gender
• Cord blood product manufactured by the NCBP (at least one, if the graft contains more than one units)
Exclusion Criteria:
• Patients who are receiving licensed cord blood products (only)
• Patients who are receiving unlicensed cord blood products from other banks (only)
• Patients who are transplanted at non-US transplant centers
• Patients who are receiving cord blood products that will be "manipulated" post-thaw (e.g., ex vivo expansion, incubation in vitro, etc.)
BIOLOGICAL: unlicensed CBU
Infusion Reactions
cord blood, transplantation, stem cells, adverse event
Phase III DAS181 Lower Tract PIV Infection in Immunocompromised Subjects (Substudy: DAS181 for COVID-19): RCT Study
Caitlin Caitlin Brammer - Caitlin.Brammer@cchmc.org
ALL
PHASE3
NCT03808922
Inclusion Criteria:
• At the time of randomization, requires supplemental oxygen ≥2 LPM due to hypoxemia.
• Immunocompromised, as defined by one or more of the following: * Received an autologous or allogeneic hematopoietic stem cell transplantation (HSCT) at any time in the past * Received a solid organ transplant at any time in the past * Has been or is currently being treated with chemotherapy for hematologic malignancies (e.g., leukemia, myeloma, lymphoma) and/or solid tumor malignancies (e.g., lung, breast, brain cancer) at any time in the past * Has an immunodeficiency due to congenital abnormality (only applicable to subjects age \< 18 years old) or pre-term birth (only applicable to subjects age ≤ 2 years old)
• Has, within 3 days prior to randomization, a confirmed LRTI with a sialic acid dependent respiratory virus
• If female, subject must meet one of the following conditions: * Not be of childbearing potential or * Be of childbearing potential and have a negative urine/serum pregnancy test and agrees to practice an acceptable method of contraception
• Non-vasectomized males are required to practice effective birth control methods
• Capable of understanding and complying with procedures as outlined in the protocol
• Provides signed informed consent prior to the initiation of any screening or study-specific procedures For COVID-19 sub study:
• Be ≥18 years of age
• Provide adequate medical history to permit accurate stratification (but health status may be healthy, high-risk conditions, or immunocompromised).
• Prior to SARS CoV 2 infection, has the ability to carry out self-care activities of daily living (basic ADL)
• Have lower respiratory tract infection (LRTI) confirmed by CT imaging, with or without contrast, to involve at least 2 lobes of the lung.
• Has laboratory-confirmation of the presence of SARS CoV 2 in the respiratory tract by at least one of the following samples
• Satisfy inclusion criteria #1, 4, 5, 6, 7 of the main study
Exclusion Criteria:
• Subjects may not be on hospice care or, in the opinion of the investigator, have a low chance of survival during the first 10 days of treatment
• Subjects with Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), or Alkaline Phosphatase (ALP) ≥3x ULN and Total Bilirubin (TBILI) ≥2x ULN Note: Subjects with ALT/AST/ALP ≥ 3x ULN AND TB ≥2x ULN that have been chronically stable (for \>1 year on more than one assessments) due to known liver pathology including malignancy (primary or metastasis), chronic medications, transplantation, or chronic infection will not be excluded
• Female subjects breastfeeding or planning to breastfeed at any time through 30 days after the last dose of study drug
• Subjects taking any other investigational drug used to treat pulmonary infection.
• Psychiatric or cognitive illness or recreational drug/alcohol use that, in the opinion of the principal investigator, would affect subject safety and/or compliance
• Subjects with known hypersensitivity to DAS181 and/or any of its components
• Subjects with severe sepsis due to either their baseline SAD-RV infection or a concurrent viral, bacterial, or fungal infection and meet at least one of the following criteria: * Has evidence of vital organ failure outside of the lung (e.g., liver, kidney) * Requires vasopressors to maintain blood pressure For COVID-19 sub study:
• Subjects requiring invasive mechanical, Bi-PAP or CPAP ventilation at randomization.
• Subjects receiving any other investigational or empiric treatment for SARS-2-CoV (either as part of a clinical trial or under emergency approval (approved agents for the management of symptoms, e.g., fever, are permitted).
• Subjects who are known HIV-positive (and not undetectable at most recent HIV RNA assessment)
• Subjects who are currently taking immunomodulating biologics (e.g, interferons, interleukin)
• Subjects with severe sepsis due to either their SARS-CoV-2 infection or a concurrent viral, bacterial, or fungal infection and meeting at least one of the following criteria: * Have evidence of vital organ failure outside of the lung (e.g., liver, kidney) * Require vasopressors to maintain blood pressure
• Subjects meeting exclusion criteria #2, 3, 5 and 6 of the main study
DRUG: DAS181, DRUG: Placebo, DRUG: DAS181 COVID-19, DRUG: DAS181 OL
Lower Respiratory Tract Infection, Parainfluenza, Immunocompromised, COVID-19
Parainfluenza, PIV, Immunocompromised, Lower Respiratory Tract Infection, LRTI, COVID19, SARS-CoV-2, Coronavirus, Ansun
Abatacept for the Treatment of Common Variable Immunodeficiency With Interstitial Lung Disease (ABCVILD)
Michael Jordan - Michael.Jordan@cchmc.org
ALL
4 years and over
PHASE2
NCT04925375
Inclusion Criteria:
• Diagnosis of CVID according to the international consensus document (ICON)
• Age 4 years or above
• Serum IgG at least 2 standard deviations below the age adjusted normal
• Decreased serum IgA and/or serum IgM
• Abnormal specific antibody response to immunization
• Exclusion of secondary immunodeficiency
• On replacement immunoglobulin for at least 6 months and willing to maintain throughout study
• Granulomatous-lymphocytic interstitial lung disease with a lymphocytic component diagnosed by lung biopsy prior to study entry, wedge biopsy preferred.
• Persistence or worsening of interstitial lung disease measured on serial CT imaging of the lung at least 6 months apart, with the latest assessment within 3 months of study entry.
• Signed written informed consent
• Willing to allow storage of biological specimens for future use in medical research.
• Female subjects of childbearing potential must agree to an effective form of birth control such as hormone based contraceptive, intrauterine device, condoms/barrier, surgically sterile partner, or abstinence.
• Fertile, non-vasectomized males with a female partner of childbearing potential should use condoms throughout the study and for 3 months after the last dose
Exclusion Criteria:
• History of hypersensitivity to abatacept or any of its components
• Has received any lymphocyte depleting agents including anti-CD20 monoclonal antibodies, alemtuzumab, ATG in the preceding 6 months
• Has received abatacept, cyclophosphamide, tumor necrosis factor inhibitors, or pulse steroids (defined as \>15mg/kg/day of methylprednisone or corticosteroid equivalent) within the past 3 months
• Have started or increased any of the following immune modulating drugs within 3 months of enrolling and 3 months from initial CT chest: azathioprine, cyclosporine, tacrolimus, mercaptopurine, methotrexate, mycophenolate mofetil, or sirolimus
• History of HIV infection (positive PCR)
• Chronic untreated hepatitis B or C (positive PCR)
• Active tuberculosis (TB) by positive QuantiFERON gold. If history of latent TB, then must supply evidence of completing treatment.
• Persistent Epstein-Barr Virus (EBV) load ≥ 1,000 units/mL blood checked twice at least 1 month apart
• Other uncontrolled infections
• Live vaccine given within 6 weeks of the start of the trial
• Malignancy or treated for malignancy within the past year
• Currently pregnant or breast feeding
• Life expectancy less than 1 month
• Subjects unwilling to self-administer or have a parent/caregiver self-administer subcutaneous injections at home
• Other conditions that the investigators feel contraindicate participation in the study Inclusion criteria for Extended Treatment Plan: * Patients must have completed the abatacept for the treatment of Interstitial Lung Disease in Common Variable Immunodeficiency (ABCVILD) trial * Patients must have demonstrated positive response to abatacept. * Patients must provide informed consent to participate in the Extended Treatment Plan. Exclusion criteria for Extended Treatment Plan: • Patients who experienced SAEs during the original trial, and such SAEs were determined as related to treatment, or patients who in the opinion of the investigator would not benefit from the extended treatment option.
DRUG: Abatacept, OTHER: Placebo
Interstitial Lung Disease, Common Variable Immunodeficiency
High vs.Standard Dose Influenza Vaccine in Pediatric Solid Organ Transplant (SOT) Recipients (PSOT)
Kerrigan Perkins - kerrigan.perkins@cchmc.org
ALL
3 years to 17 years old
PHASE2
NCT05947071
Inclusion Criteria:
• Male or female, 3-17 years of age at time of enrollment
• Pediatric kidney, heart, and/or liver transplant recipient ≥1 month and \<24 months post-transplant at the time of study immunization * Note: Inclusion of recipients of multiple organs is permitted but is limited to recipients of any combination of organs including kidney, heart and/or liver * Note: Participants undergoing re-transplantation are permitted
• Anticipated to be available for duration of the study
• Available by telephone, email, or text message
Exclusion Criteria:
• Inability (i.e. not able to understand and provide consent) or unwillingness of a participant/parent/legal guardian to give written informed consent or comply with study protocol
• History of severe hypersensitivity to influenza vaccination or anaphylaxis to eggs/egg protein
• History of severe latex hypersensitivity
• History of Guillain-Barre syndrome
• History of lung or intestine transplant
• HIV positive patients (testing within 24 months of enrollment)
• Receipt of current season's influenza vaccine post-transplant prior to enrollment in the study
• Currently pregnant or lactating (females of childbearing age may be enrolled based on self-report, urine pregnancy test must be performed prior to each influenza vaccine)
• Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.
BIOLOGICAL: Standard Dose Quadrivalent Inactivated Influenza Vaccine, BIOLOGICAL: High Dose Quadrivalent Inactivated Influenza Vaccine
Immunization, Infection, Transplantation Infection, Influenza
Influenza, Vaccination, Immunization, High Dose, Fluzone, Standard Dose, Influenza, Human, Communicable Diseases, Pediatric transplantation
Phase I/II Trial of Lentiviral Gene Transfer for SCID-X1 With Low Dose Targeted Busulfan Conditioning
Joan Moore - joan.moore@cchmc.org
MALE
0 years to 5 years old
PHASE1
NCT03311503
Inclusion Criteria:
\- 1. Diagnosis of SCID-X1 based on immunophenotype and lack of T cell function (proliferation to PHA \<10% of the lower limit of normal for the laboratory) AND confirmed by a mutation in IL2RG 2. Lack of an HLA identical (A, B, C, DR, DQ) related donor 3. Age 5 years old or younger 4. Signed informed consent 5. Documentation of willingness to follow up for 15 years post-infusion as currently required by the FDA 6. If the patient has previously undergone allogeneic transplant, lack of donor T cell engraftment must be documented.
7\. Age at least 8 weeks by the time of busulfan administration
Exclusion Criteria:
• Patients with an active, therapy-resistant infection. Infections that are known to be highly morbid in SCID patients will be considered active and therapy-resistant if the infectious agent is repeatedly isolated despite a minimum of 2 weeks of appropriate therapy and is associated with significant organ dysfunction (including but not limited to abnormalities listed below).
• Mechanical ventilation including continuous positive airway pressure
• Abnormal liver function defined by AST and ALT \>10 times the upper range of normal OR Bilirubin \>2 mg/dL
• Shortening fraction on echocardiogram \<25% or ejection fraction \<50%
• Renal failure defined as glomerular filtration rate \<30 ml/min/1.73 m2 or dialysis dependence
• Uncontrolled seizure disorder
• Encephalopathy
• Documented coexistence of any disorder known to affect DNA repair
• Diagnosis of active malignant disease other than EBV-associated lymphoproliferative disease
• Patients with evidence of infection with HIV-1
• Major (life-threatening) congenital anomalies. Examples of "major (life-threatening) congenital anomalies" include, but are not limited to: unrepaired cyanotic heart disease, hypoplastic lungs, anencephaly or other major central nervous system malformations, other severe non-repairable malformations of the gastrointestinal or genitourinary tracts that significantly impair organ function.
• Other conditions which in the opinion of the P.I. or co-investigators, contra-indicate collection and/or infusion of transduced cells or indicate patient's inability to follow the protocol. These may include for example clinical ineligibility to receive anesthesia, severe deterioriation of clinical condition of the patient after collection of bone marrow but before infusion of transduced cells, or documented refusal or inability of the family to return for scheduled visits. There may be other unforeseen rare circumstances that would result in exclusion of the patient, such as sudden loss of legal guardianship \-
BIOLOGICAL: autologous CD34+ cell transduced with G2SCID vector
Severe Combined Immunodeficiency, X Linked, Gene Therapy
lentiviral, Gene therapy, busulfan
Extended vs Short-term Abatacept Dosing for Graft Versus Host Disease Prophylaxis (ABA3)
Celeste Dourson - Celeste.Dourson@cchmc.org
ALL
2 years and over
PHASE2
NCT04380740
Inclusion Criteria:
• Must be at least 2 years old and weigh 10 kg.
• Must have a willing unrelated adult donor (bone marrow or peripheral blood). Donors may have a single mismatch (i.e. be a 7/8) and this mismatch may be at the allele or antigen level; however, donors with allele level disparity should be given preference over those with antigen level disparity. Patients for whom a donor is available with disparity only in the host versus graft direction (because of recipient homozygosity), will not be eligible, since this mismatching does not increase the risk for GVHD. Centers may perform extended typing (e.g. DQB1 and DPB1) according to institutional practices and use these results in selecting donors; however, it is recommended that this extending typing be used only to select between donors who are equally well matched with the recipient at the A, B, C and DRB1.
• All patients and/or their parents or legal guardians must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
• Must have a hematologic malignancy treatable by HCT (except for those stipulated below under study Exclusion Criteria), which is in remission by standard testing (no patients in relapse will be included).
• Patients with an inherited predisposition to leukemia or otherwise hematologic malignancies that have not been associated with predisposition to transplant morbidities or non-hematologic cancers.
• Karnofsky performance score or Lanskey Play-Performance Scale score \>/= 80. * If the patient does not meet defined eligibility requirements, the PI/study committee must be contacted to determine eligibility.
Exclusion Criteria:
• Patients with the following hematologic malignancies will be excluded: Chronic Lymphocytic Leukemia, Myeloma and Primary Myelofibrosis.
• Active Relapse (\>5% blasts) of their primary malignancy.
• For patients with Acute Lymphocytic Leukemia (ALL) with pre-transplant MRD testing performed as standard practice at the treating institution, patients with MRD \>0.01% will be ineligible.
• For patients with Acute Myeloid Leukemia (AML) with pre-transplant MRD testing as standard of practice at the treating institution, patients with any MRD status are eligible and should be enrolled at the discretion of provider.
• For patients with MDS, those with \>5% blasts will be excluded.
• Prior allogeneic HCT.
• Uncontrolled viral, bacterial, fungal or protozoal infection at the time of study enrollment.
• HIV infection.
• Serious psychiatric disease including schizophrenia, bipolar disorder and severe depression.
• Prisoners or others who are compulsorily detained.
• Any patient with a known or suspected inherited predisposition to cancer should be discussed with the study team prior to screening for eligibility.
• Patients with a known inherited or constitutional predisposition to transplant morbidities, including, but not limited to Fanconi Anemia, Dyskeratosis Congenita, Shwachman-Diamond Syndrome and Down Syndrome will be excluded.
• Patients with known inherited or constitutional predisposition to non-hematologic cancers including, but not limited to Li-Fraumeni syndrome, BRCA1 and BRCA2 mutations will be excluded.
• Patients with active non-hematological malignancies (except non-melanoma skin cancers) or those with non-hematological malignancies (except non-melanoma skin cancers) who have been rendered with no evidence of disease, and are disease free for \<2 years.
• Incompletely treated active tuberculosis Infection.
• Pregnancy (positive serum b-HCG) or breastfeeding.
• Estimated GFR of \< 50 mL/min/1.73m2.
• Cardiac ejection fraction \< 50 (using M-Mode if assessment is done by ECHO)
• T.bilirubin \> 2 × upper limit of normal or ALT \> 4 × upper limit of normal or unresolved veno-occlusive disease.
• Pulmonary disease with FVC, FEV1 or DLCO parameters \<45% predicted (corrected for hemoglobin) or requiring supplemental oxygen. Children who are developmentally unable to perform pulmonary function testing will be assessed solely on their need for supplemental oxygen.
• Presence of antibodies to a mismatched donor HLA antigen (please refer to Section 3.4.g).
• Patients who have developed severe AGVHD, severe CGVHD or relapse will be excluded at the time of randomization.
• Exclusion Criteria Prior to Randomization (prior to 5th dose of abatacept/placebo):
• Severe allergic reaction during the first 4 doses of abatacept
• If any clinical events occur that preclude further dosing of abatacept, those patients will be deemed ineligible for randomization
DRUG: Placebo, DRUG: Abatacept
Graft Vs Host Disease
Safety of RSV Preventive Monoclonal Antibody
Cathy Boyce - catherine.boyce@cchmc.org
ALL
6 weeks to 30 weeks old
PHASE4
NCT07158814
Inclusion Criteria:
* Infants ≥ 6 weeks to \<30 weeks of age at the time of enrollment
* Infants eligible for RSV monoclonal antibody and at least one routine childhood vaccine in outpatient clinic
* The parent/legal guardian must be willing and capable of providing permission for their infant to participate through the written informed consent process
* Parent/legal guardian must be able to read and comprehend English or Spanish
* The parent/legal guardian must be available for follow-up study contact by telephone from enrollment to completion of the study period
* The parent/legal guardian must agree to sign a medical record release for the infant so that study personnel may obtain medical information about the infant's health (if needed)
* The parent/legal guardian must be willing to delay their child's receipt of RSV monoclonal antibody up to two weeks from the scheduled date and to return for a second visit to receive the deferred RSV monoclonal antibody
Exclusion Criteria:
* Known contraindication or precaution to RSV monoclonal antibody or other routine vaccines being administered
* Received any vaccine within 14 days prior to enrollment and the first immunization day in this study
* Known previous receipt of RSV monoclonal antibody
* Received any experimental/investigational agent (vaccine, drug, biologic, device, blood product, or medication) within 28 days prior to immunization in this study or expects to receive an experimental/investigational agent within the follow-up time period (8 days after the second immunization in this study)
* A moderate to severe acute illness and/or a reported temporal temperature greater than or equal to 100.4°F (38.0°C) within 48 hours prior to enrollment or a temporal temperature (measured by temporal artery thermometer) greater than or equal to 100.4°F (38.0°C) at the time of enrollment. (This may result in a temporary delay of immunization)
* Receipt of an antipyretic medication (acetaminophen or ibuprofen) within 48 hours prior to enrollment (This may result in a temporary delay of immunization)
* Planned receipt of a prophylactic antipyretic medication on the day of and/or days following immunization. This exclusion does not apply if the parent/legal guardian indicates they might administer antipyretics after immunization in response to fever or pain
* Has any condition that would, in the opinion of the site investigator, place the participant at an unacceptable risk of injury or render the participant unable to meet the requirements of the protocol
* Anyone who is a first-degree relative of any research study personnel
* The infant is born to a mother who received a maternal RSV immunization more than 14 days prior to delivery and is not eligible for RSV preventative monoclonal antibody
* Bleeding disorder or condition associated with prolonged bleeding that would present as a safety risk per opinion of the investigator
* History of severe adverse reaction associated with a vaccine and/or severe allergic reaction to any component of the vaccines or RSV monoclonal antibody
* Has an active neoplastic disease, or a history of any hematologic malignancy
* History of a severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a component of a vaccine administered on the day of study enrollment
* Immunosuppression as a result of an underlying illness or treatment or use of anti-cancer chemotherapy or radiation therapy since birth
* For infants receiving DTaP vaccine (alone or combination vaccine): Encephalopathy (e.g., coma, decreased level of consciousness, prolonged seizures), not attributable to another identifiable cause, within 7 days of administration of previous dose of DTaP
* Intention to receive non-live or live vaccines during the 4 weeks after Visit 1; vaccines may be administered after enrollment if deemed a personal or public health priority by the health care provider caring for this patient or the study team
* Long term (at least 14 days of prednisone 2 mg/kg/day or equivalent other glucocorticoid) use of any parenteral steroids within the 6 months prior to enrollment (topical, nasal and inhaled steroids are allowed) DRUG: Respiratory Syncytial Virus (RSV) Preventive Monoclonal Antibody
Fever, Adverse Event Following Immunisation
Respiratory Syncytial Virus (RSV), Fever Following Immunization, RSV Monoclonal Antibody
Stress Hydrocortisone In Pediatric Septic Shock (SHIPSS)
Abigayle Gibson - abigayle.gibson@cchmc.org
ALL
1 month to 17 years old
PHASE3
NCT03401398
Inclusion Criteria:
A child receiving treatment in a pediatric intensive care unit is eligible for recruitment into SHIPSS if she/he meets all of the following inclusion criteria:
• Age is at least 1 month (with corrected gestational age ≥42 weeks), but less than 17 years and 8 months of age
• A documented focus of infection or a strong suspicion of infection at PICU admission, or for patients who develop septic shock during PICU stay, at the onset of the septic shock event
• Surveillance cultures (e.g. blood, urine, cerebral spinal fluid, wound) and/or other microbial diagnostic tests have been obtained
• One or more antimicrobials have been prescribed
• Core temperature \>38.5 C or \<36.0 C or leukocytosis or leukopenia (as defined by the local laboratory) or a left-shifted leukocyte differential (\>10% immature granulocyte forms) or a neutrophil count of \<0.5 x 109 cells per litre documented at least once within the 24 hours preceding screening
• Treatment with a continuous infusion of vasoactive-inotropic agent(s) to maintain mean or systolic arterial blood pressure above the age-appropriate target set by the treating clinician
• Administration of two or more vasoactive-inotropic agents at any dose or epinephrine or norepinephrine infusion(s) alone at greater than or equal to 0.10 mcg/kg/min for \>1 hour.
Exclusion Criteria:
A child receiving treatment in a pediatric intensive care unit for sepsis is ineligible for enrollment into SHIPSS if she/he meets any of the following exclusion criteria:
• All inclusion criteria have been present for \> 12 hours
• Attending physician expects to prescribe systemic corticosteroids for an indication other than septic shock
• Patient has received any doses of systemic corticosteroids during treatment for sepsis
• Enrolled concurrently in a competing interventional clinical trial (formal assessment to be conducted by SHIPSS Core Committee for each potential competing trial)
• Etomidate or ketoconazole treatment within past 48 hours
• Patient in whom steroids are contraindicated at time of screening (e.g. treatment for systemic fungal infection, cerebral malaria, strongyloides)
• Known or suspected hypothalamic, pituitary or adrenal disease (including patient has received acute or chronic corticosteroid administration and the physician intends to provide corticosteroid for suspected adrenal suppression)
• Attending physician, PICU care team, or legally recognized guardians not committed to full treatment and resuscitation at the time of screening
• Patient documented to be pregnant
• Previous enrollment in the SHIPSS study
• Patient admitted directly to the PICU with a thermal burn who has been in the PICU for \<72 hours prior to meeting SHIPSS inclusion criteria.
• (U.S. sites only) Patient in the custody of US protective services
• Patient being evaluated for brain death
• Vasoactive-inotropic agents prescribed solely for an indication other than septic shock
• Confirmed dengue fever
DRUG: Hydrocortisone, sodium succinate, DRUG: Normal saline
Septic Shock
hydrocortisone, refractory septic shock, sepsis, new/progressive MODS, mortality, health-related quality of life, corticosteroid adverse events, sepsis biomarkers
Non-Invasive Diagnosis of Pediatric Pulmonary Invasive Mold Infections (DOMINIC)
Caitlin Brammer - caitlin.brammer@cchmc.org
ALL
120 days to 21 years old
NCT03827694
Inclusion Criteria:
* Males or females age \> 120 days and \< 22 years at any participating site
* Have at least one of the following conditions associated with a known high incidence of IFI: hematopoietic stem cell transplantation (HSCT), aplastic anemia, bone marrow failure, primary or acquired immune deficiency, or malignancy
* New (last 96 hours) radiographic evidence of at least one of the following: at least one nodular lesion greater than or equal to 5 mm in size, a wedge-shaped and segmental or lobar consolidation, a cavitary lesion, a lesion with a halo sign, a lesion with a reverse halo sign, or a lesion with an air crescent sign
* Prolonged neutropenia (absolute neutrophil count \< 500 cells/µl for a period of ≥ 5 consecutive days) in 30 days prior to and including the day of qualifying chest MRI or CT scan date OR currently receiving systemic therapy for acute or chronic graft-versus-host disease (GVHD) OR presence of neutrophil dysfunction because of underlying acquired or primary immune deficiency (e.g. chronic granulomatous disease) on the date of the qualifying chest MRI or CT scan
* Subject consent or parental/guardian permission (informed consent) and if appropriate, child assent
Exclusion Criteria:
* Weight \<3 kg, so as to not exceed 3 ml/kg in a single blood draw
* Previous inclusion in this study DIAGNOSTIC_TEST: Non-Invasive Testing for PIFI
Pulmonary Invasive Fungal Infections, Pulmonary Invasive Aspergillosis
Health-E You Efficacy Trial for Male Adolescents
Emmanuel Chandler - emmanuel.chandler@cchmc.org
MALE
13 years to 21 years old
NA
NCT06525064
Inclusion Criteria:
* Assigned male sex at birth
* Age 13 to 21 years old
* English and/or Spanish as preferred language to read, listen, and converse
* Self-reported engagement in vaginal and/or anal sex in the past 12 months
* Access to phone or internet for follow-up study activities
Exclusion Criteria:
* Aged 12 or younger or older than 21
* Primary language other than English or Spanish
* Not able to provide informed consent
* Unable to communicate due to cognitive, mental, language, or other difficulties
* Not sexually active, engaged in oral sex only, or more than 12 months have passed since last vaginal and/or anal sex.
* Previous participation in a Health-E You study activity or the app OTHER: Health-E You app
Sexually Transmitted Diseases, Sexual Health, Reproductive Health
male adolescent, condom use, mhealth
Sinus Disease in Young Children With Cystic Fibrosis
Megan Schmitt - megan.schmitt@cchmc.org
ALL
2 years to 8 years old
NCT06191640
Inclusion Criteria:
HEMT Group:
* Children with documentation of a CF diagnosis
* Age 2-8 years old at first study visit
* CFTR mutation consistent with FDA labeled indication of highly effective modulator therapy (ivacaftor or elexacaftor/tezacaftor/ivacaftor)
* Clinician intent to prescribe ivacaftor or ETI so that enrollment is before start of HEMT
Non-HEMT/Control Group:
* Children with documentation of a CF diagnosis
* Age 2-8 years at first study visit
* Ineligible for highly effective modulator therapy (ivacaftor or elexacaftor/tezacaftor/ivacaftor) based on CFTR mutation or clinical decision not to initiate HEMT if eligible
Exclusion Criteria:
For Both Groups:
* Use of an investigational drug within 28 days prior to the first study visit
* Use of ivacaftor or elexacaftor/tezacaftor/ivacaftor within the 180 days prior to and including the first study visit
* Use of chronic oral corticosteroids within the 28 days prior to and including the first study visit.
* Sinus surgery within 180 days prior to the first study visit DRUG: Ivacaftor or elexacaftor/tezacaftor/ivacaftor
Cystic Fibrosis in Children, Cystic Fibrosis, Chronic Rhinosinusitis (Diagnosis), Olfactory Disorder, Olfactory Impairment
Cystic Fibrosis, Chronic Rhinosinusitis, Olfactory Dysfunction
A Study to Evaluate the Safety and Tolerability, Pharmacokinetics, and Antiviral Activity of Maribavir for the Treatment of Cytomegalovirus (CMV) Infection in Children and Adolescents Who Have Received a Hematopoietic Stem Cell Transplant (HSCT) or a Solid Organ Transplant (SOT)
Kerrigan Perkins - kerrigan.perkins@cchmc.org
ALL
Up to 17 years old
PHASE3
NCT05319353
Inclusion Criteria:
* Parent/both parents or legally authorized representative (LAR) must provide signature of informed consent and there must be documentation of assent by the participant, as age appropriate, before completing any study-related procedures.
* Be a male or female child or adolescent \< 18 years of age at the time of consent. For participants in Cohort 3 only (0 to \<6 years) must have a gestational age of at least 39 weeks and a minimum weight of 5 kg.
* Be a recipient of an SOT or an HSCT that is functioning at the time of screening.
* Have a documented CMV infection which may be a first episode of post-transplant CMV viremia (primary or reactivation) or refractory to other anti-CMV treatments, with a CMV DNA screening value of \>= 1365 International Units per milliliter (IU/mL) in whole blood or \>= 455 IU/mL in plasma in 2 consecutive assessments separated by at least 1 day, as determined by local laboratory quantitative polymerase chain reaction (qPCR) or comparable quantitative nucleic acid amplification test (qNAAT) results. Quantitative assays must be standardized to the World Health Organization (WHO) CMV International Standard. Both samples must be taken within 14 days of first dose of study drug, with the second sample obtained within 5 days prior to first dose of study drug. The same laboratory and same sample type (whole blood or plasma) must be used for both assessments. If documented and verified values are available in medical history that fulfill this criterion entirely, they may be used instead.
* Have all the following results as part of screening laboratory assessments:
* Absolute neutrophil count \>= 500 per cubic millimeter (/mm\^3) (0.5 × 10\^9 per liter \[/L\])
* Platelet count \>= 15,000/mm\^3 (15 × 10\^9/L)
* Hemoglobin \>= 8 grams per deciliter (g/dL) (\>=80 grams per liter \[g/L\]).
* Have an estimated glomerular filtration rate (creatinine-based Bedside Schwartz equation) \>= 30 milliliters per minute (mL/min) /1.73 meter square (m\^2).
* Be a female of nonchildbearing potential. If a female of childbearing potential, have a negative serum human chorionic gonadotropin (hCG) or beta-human chorionic gonadotropin (β-hCG) pregnancy test at screening. Males, or nonpregnant, nonlactating females who are sexually active must agree to comply with the applicable contraceptive requirements of this protocol during the study treatment administration period and for 90 days after the last dose of study treatment.
* Have life expectancy of \>= 8 weeks.
* Be willing and have an understanding and ability to fully comply with the study procedures and restrictions defined in the protocol. For younger children, the parent/both parents or LAR must meet this criterion.
* Participants must have a confirmed negative human immunodeficiency virus (HIV) test result within 3 months of first dose of study drug or, if unavailable, be tested by a local laboratory during the screening period.
Exclusion Criteria:
* Have CMV tissue invasive disease involving the central nervous system (CNS) or retina as assessed by the investigator at the time of screening.
* Have uncontrolled other type of infection as assessed by the investigator on the date of enrollment.
* Have a history of clinically relevant alcohol or drug abuse that may interfere with treatment compliance or assessments with the protocol as determined by the investigator.
* Be receiving valganciclovir, ganciclovir, cidofovir, foscarnet, leflunomide, letermovir, or artesunate when study treatment is initiated, or anticipated to require one of these agents during the 8-week treatment period.
* Have a known hypersensitivity to maribavir or to any excipients.
* Have severe vomiting, diarrhea, or other severe gastrointestinal (GI) illness within 24 hours prior to the first dose of study treatment or a GI absorption abnormality that would preclude administration of oral medication.
* Require mechanical ventilation or vasopressors for hemodynamic support at baseline (Visit 2/Day 1/Week 0).
* Be pregnant (or expecting to conceive) or nursing.
* Have previously completed, discontinued, or have been withdrawn from this study.
* Have received any investigational agent or device within 30 days before initiation of study treatment (includes CMV specific T-cells) or plan to receive an investigational agent or device during the study.
Previously approved agents under investigation for additional indications are not exclusionary.
* Have previously received maribavir or CMV vaccine at any time.
* Have any clinically significant medical or surgical condition that, in the investigator's opinion, could interfere with interpretation of study results, contraindicate the administration of the study treatment, or compromise the safety or well-being of the participant.
* Have severe liver disease (Child-Pugh score of \>= 10).
* Have serum aspartate aminotransferase greater than (\>) 5 times upper limit of normal (ULN) at screening, or serum alanine aminotransferase \> 5 times ULN at screening, or total bilirubin \>= 3.0 times ULN at screening (except for documented Gilbert's syndrome), as analyzed by local laboratory.
* Have positive results for HIV.
* Have active malignancy with the exception of nonmelanoma skin cancer, as determined by the investigator. Participants who experience relapse or progression of their underlying malignancy (for which HSCT or SOT was performed), as determined by the investigator, are not to be enrolled.
* Be undergoing treatment for acute or chronic hepatitis B or hepatitis C.
* Requiring ongoing treatment with or an anticipated need for treatment with a strong cytochrome P450 3A (CYP3A) inducer.
* Have a low body weight where total blood volume (TBV) required during study participation will exceed 1 percent (%) TBV per study visit or 3% TBV over a 4-week period. DRUG: Maribavir
Cytomegalovirus (CMV)
Sleep and Adolescent Vaccine Immunogenicity Pilot/Observational Study (SAVI)
Dean Beebe - BEEBD0@cchmc.org
ALL
11 years to 12 years old
NCT07636525
Inclusion Criteria:
* Healthy 11-12 years olds who have neither had initial meningococcal vaccination nor known exposure to meningococcal illness.
Exclusion Criteria:
* Condition or treatment resulting in immunosuppression
* Prior severe vaccine reaction
* Symptoms of clinical insomnia or organic sleep disorder
* Known neurologic condition or intellectual/developmental disability
* Use of a medication that impacts sleep
* Average nightly sleep of 8-8.99 hours (between the two groups)
* Daily intake of \>1 coffee or "energy drink" or \>2 caffeinated sodas. Vaccination
Sleep
A Phase 3 Trial to Compare IV BCV Versus IV CDV for Treatment of Adenovirus Infection After Allo-HCT (ENOVIA)
Brady Landon - brady.landon@cchmc.org
ALL
2 month(s) and over
PHASE3
NCT07387367
Inclusion Criteria:
• Male and female, post-allo HCT within last 180 days, aged 2 months and older at time of signing informed consent form.
• Subject/Guardian willing and able to understand and provide written informed consent to participate in the study.
• In the investigator's judgement, the subject's clinical condition justifies treatment with IV BCV or IV CDV for AdV infection.
• Has adenoviremia, based on any of: * AdV viremia DNA ≥10,000 IU/mL, OR * Two consecutive and rising AdV viremia DNA results of ≥1,000 IU/mL at screening, OR * AdV viremia DNA of ≥1,000 IU/mL, AND 1\. Lymphocyte count \<180/mm3, OR 2. Received T cell depletion, cord blood, or haploidentical transplant, OR 3. prior alemtuzumab, OR 4. anti-thymocyte globulin (ATG)
Exclusion Criteria:
• Subject received an allo-HCT with a matched sibling donor
• Subject received more than 5 mg/kg of CDV for any reason in the 21 days prior to first dose of study drug.
• Subject is allergic or hypersensitive to IV BCV or IV CDV or any of their components.
• Subject received anti-AdV-specific cell-based therapy within 3 weeks prior to W1D1 or an anti-AdV vaccine at any time.
• Subject has participated in any other investigational study within 30 days (or within 5.5 half-lives of the investigational product, whichever is longer) before signing the informed consent form (ICF), is currently participating in another interventional treatment trial with an investigational agent or is using an investigational device at the time of Screening.
DRUG: cidofovir, DRUG: Brincidofovir
Adenovirus Infections
Brincidofovir, Cidofovir, Adenovirus, allo-HCT, BCV-PA02, ENOVIA
Multi-Center Molecular Diagnosis and Host Response of Respiratory Viral Infections in Pediatric Transplant Recipients
Lara Danziger-Isakov, MD - Lara.Danziger-Isakov@cchmc.org
ALL
Up to 18 years old
NCT05550298
Recipient Inclusion Criteria
* Less than 18 years at the time of anticipated transplant
* Participant meets one of the following criteria:
• scheduled to receive allogeneic hematopoietic cell transplant within 14 days of enrollment or
• Scheduled to or received solid organ transplant within 7 days before or after enrollment * Participant is receiving care at the time of enrollment at one of the study participating institutions. * Parent/guardian willing and able to provide informed consent, and if appropriate, child willing and able to provide informed assent. Donor Inclusion Criteria * Donor for HCT recipient enrolled on the VIPER study. * Willing and able to provide informed consent.
• scheduled to receive allogeneic hematopoietic cell transplant within 14 days of enrollment or
• Scheduled to or received solid organ transplant within 7 days before or after enrollment * Participant is receiving care at the time of enrollment at one of the study participating institutions. * Parent/guardian willing and able to provide informed consent, and if appropriate, child willing and able to provide informed assent. Donor Inclusion Criteria * Donor for HCT recipient enrolled on the VIPER study. * Willing and able to provide informed consent.
Exclusion Criteria:
Recipient Exclusion Criteria
None
Donor Exclusion Criteria
* Is not an HCT donor for a participant enrolled on the VIPER study.
* Not available to provide pre-transplant research blood sample. Hematopoietic Cell Transplant, Solid Organ Transplant, Respiratory Viral Infection
A Phase 3 Study of Revaccination in Subsequent Pregnancies With Bivalent RSV Vaccine and Duration of Protection of a Single Dose
Benjamin Kercsmar - Benjamin.Kercsmar@cchmc.org
ALL
Not specified
PHASE3
NCT06866405
Pregnant Participants-Cohort 1 and Cohort 2 Key Inclusion Criteria
* Women aged 18 to 49 who are pregnant, between 24 and 36 weeks along, and expecting one baby without known risks for complications can participate.
* Had the RSVpreF or Abrysvo vaccine during a previous pregnancy.
* Had an ultrasound scan at 18 weeks or later during their current pregnancy, with no major fetal problems detected.
* Based on their medical history, physical check-up, and the doctor's judgment, they are found suitable to join the study.
* Agrees to let their baby take part in the study and gives their permission.
* Able to sign a consent form, agreeing to follow the rules and conditions of the study.
Key Exclusion Criteria
* Received any approved or experimental RSV vaccine since their previous pregnancy.
* Has a pre-pregnancy body mass index (BMI) over 40 kg/m2.
* History of a severe bad reaction to a vaccine or a serious allergic reaction (like anaphylaxis) to any ingredient in the study vaccine or a similar vaccine.
* Current pregnancy problems or issues at the time of giving consent.
* Previous pregnancy issues or problems at the time of giving consent.
* Women who are breastfeeding at the time of enrollment
Infant Participants
* Proof that the parent(s) or legal guardian(s) has signed and dated a consent form.
* Parent(s) or legal guardian(s) must agree to attend scheduled visits and follow the study plan, including laboratory tests and other procedures.
Nonpregnant Participants-Cohort 3 Key Inclusion Criteria
* Have already received one dose of the RSVpreF vaccine during their previous pregnancy as part of the Pfizer clinical trial, and the results from that time can be used for this study.
* Able to sign a consent form, agreeing to follow the rules and requirements of the study.
Key Exclusion Criteria
* Received any approved or experimental RSV vaccine after participating in the Pfizer clinical trial.
* Taking part in other studies with new drugs within 28 days before giving consent or during the study period.
BIOLOGICAL: RSVpreF, BIOLOGICAL: Placebo
RSV Infection
Pregnancy, RSV vaccine, RSV, Maternal immunization
Follow-up Automatically vs. As-Needed Comparison (FAAN-C) Trial (FAAN-C)
Holly Flake - Holly.Flake@cchmc.org
ALL
Up to 18 years old
NA
NCT05471908
Inclusion Criteria:
* Age \<18 years at the time of randomization
* Hospitalization due to a primary diagnosis of pneumonia, skin and soft tissue infection, acute gastroenteritis, or urinary tract infection.
* Parent speaks English or Spanish.
Exclusion Criteria:
* Presence of a comorbid disease that is both chronic and complex
* Principal disease required surgical intervention (beyond superficial incision and drainage)
* Immunodeficiency
* A well-child check-up or post-hospitalization follow-up visit is already scheduled within 7 days of hospital discharge
* Parent or participant strongly prefers PRN or automatic follow-up
* A medical provider feels strongly that a post-hospitalization follow-up visit is needed within 7 days of hospital discharge
* Sibling concurrently hospitalized
* Unable to identify a clinic where the participant would receive any needed post-hospitalization follow-up
* Diagnosis of pneumonia complicated by:
o Receiving a chest tube
* Diagnosis of urinary tract infection complicated by:
* History of neurogenic bladder or urologic surgery
* Renal imaging anticipated within 7 days of hospital discharge
* Renal abscess
* Diagnosis of skin and soft tissue infection complicated by:
* Chronic wound
* Postoperative infection
* Predisposition to poor wound healing
* Discharging with a drain in place
* Complicated by necrotizing fasciitis or toxic shock syndrome
* Diagnosis of gastroenteritis complicated by:
* Hemolytic uremic syndrome BEHAVIORAL: As-needed follow up, BEHAVIORAL: Automatic follow-up
Pneumonia, Urinary Tract Infections, Soft Tissue Infections, Gastroenteritis
post-hospitalization, follow-up care, patient centered care, randomized control trial
Donor-Derived Viral Specific T-cells (VSTs) (VSTs)
Jamie Wilhelm - Jamie.Wilhelm@cchmc.org
ALL
1 month(s) and over
PHASE1
NCT02048332
Inclusion Criteria:
* Recipient must be at least 21 days after stem cell infusion
* Clinical status must allow tapering of steroids to 0.5mg/kg prednisone or other steroid equivalent
* Recipient must have achieved engraftment with ANC ≥ 500
Exclusion Criteria:
* Active acute GVHD grades II-IV
* Uncontrolled bacterial or fungal infection
* Uncontrolled relapse of malignancy requiring treatment with chemotherapy
* Infusion of ATG or alemtuzumab within 2 weeks of VST infusion BIOLOGICAL: Viral specific VST Infusion
Allogeneic Stem Cell Transplant, Viral Infection, Viral Reactivation
Epstein-Barr Virus (EBV), Adenovirus (ADV), t-cells, donor, transplant, children, cytomegalovirus (CMV), BK virus (BKV)
A Multicenter Access and Distribution Protocol for Unlicensed Cryopreserved Cord Blood Units (CBUs)
513-636-2799 - cancer@cchmc.org
ALL
NCT01351545
Inclusion Criteria:
* Disorders affecting the hematopoietic system that are inherited, acquired, or result from myeloablative treatment
* Signed informed consent (and signed assent, if applicable) obtained prior to study enrollment
* Pediatric and adult patients of any age
Exclusion Criteria:
* Patients who are receiving only licensed CBUs
* Cord blood transplant recipients at international transplant centers
* Patients who are enrolled on another IND protocol to access the unlicensed CBU(s)
* Patients whose selected unlicensed CBU(s) will be more than minimally manipulated DRUG: A multicenter access and distribution protocol for unlicensed cryopreserved cord blood units (CBUs)
Hematologic Malignancies, Inherited Disorders of Metabolism, Inherited Abnormalities of Platelets, Histiocytic Disorders, Acute Myelogenous Leukemia (AML or ANLL), Acute Lymphoblastic Leukemia (ALL), Other Acute Leukemia, Chronic Myelogenous Leukemia (CML), Myelodysplastic (MDS) / Myeloproliferative (MPN) Diseases, Other Leukemia, Hodgkin Lymphoma, Non-hodgkin Lymphoma, Multiple Myeloma/ Plasma Cell Disorder (PCD), Inherited Abnormalities of Erythrocyte Differentiation or Function, Disorders of the Immune System, Autoimmune Diseases, Severe Aplastic Anemia
Trial of Scheduled Versus Treatment Administration of Donor-Derived Viral Specific T-cells for Viral Infections After Stem Cell Transplant
Celeste Dourson - celeste.dourson@cchmc.org
ALL
PHASE2
NCT04230356
SCHEDULED ARM:
Inclusion Criteria:
* Recipient must be at least 21 days after stem cell infusion
* Clinical status must allow tapering of any steroids to \< 0.5mg/kg prednisone or other steroid equivalent
* No critical illness making VST infusion hazardous
Exclusion Criteria:
* Active acute GVHD grades II-IV.
* Uncontrolled relapse of malignancy.
* Infusion of ATG or alemtuzumab within 2 weeks prior to VST infusion. Alemtuzumab levels will be collected in the second week following stem cell infusion in patients who received alemtuzumab as part of their conditioning regimen. The level must be less than or equal to 0.15 prior to infusion of VSTs. In patients with level greater than 0.15, alemtuzumab levels can be checked serially until a level ≤ 0.15 is obtained. They would become eligible for scheduled VST infusion at that point.
TREATMENT ARM
Inclusion Criteria:
* Blood adenovirus PCR ≥1,000
* Blood CMV PCR ≥ 500
* Blood EBV PCR ≥ 9,000
* Plasma BKV PCR \>1,000
* Evidence of invasive adenovirus infection. Adenovirus infection will be defined as the presence of adenoviral positivity as detected by PCR or culture from one site such as stool or blood or urine or nasopharynx. Adenovirus disease will be defined as the presence of adenoviral positivity as detected by culture or PCR from more than 2 sites such as stool or blood or urine or nasopharynx.
* Evidence of invasive CMV infection, defined as pneumonitis, retinitis, colitis, hepatitis
* Evidence of EBV-associated lymphoproliferation (EBV-LPD) defined as proven EBV-LPD by biopsy or probable EBV-LPD defined as an elevated EBV DNA level in the blood associated with clinical symptoms (adenopathy or fever or masses on imaging) but without biopsy confirmation.
* Evidence of symptomatic BK virus infection, defined as hemorrhagic cystitis or BK nephropathy.
* No active acute GVHD grades II-IV
* No uncontrolled relapse of malignancy
* No infusion of ATG or alemtuzumab within 2 weeks of VST infusion.
* Clinical status must allow tapering of any steroids to \< 0.5mg/kg prednisone or other steroid equivalent BIOLOGICAL: Viral Specific T-cells (VSTs) Scheduled, BIOLOGICAL: Viral Specific T-cells (VSTs) Treatment
Allogeneic Stell Cell Transplant, Viral Infection
A Safety and Immunogenicity Study of CHIKV VLP Vaccine in Children.
Julie Kulhanek - Julie.Kulhanek@cchmc.org
ALL
1 year to 11 years old
PHASE3
NCT07003984
Inclusion Criteria:
• Males or females between 1 and \<12 years of age at Day 1 (day of vaccination). Note: Screening should only occur in the active/open cohorts. Please see Section 6.1 for details
• Body weight ≥6.5 kg.
• In general good health, in the opinion of the investigator, based on medical history and physical examination.
• Able and willing to provide informed assent for study participation and primary caregiver is able and willing to provide informed consent for study participation, in accordance with the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) determination and applicable federal and local regulations and guidelines.
• Able and willing to complete all scheduled visits and comply with all study procedures.
Exclusion Criteria:
• Participation or planned participation in an investigational clinical study (eg, vaccine, drug) within 30 days before Day 1 and for the duration of the study. Note: Participation in an observational study or follow-up phase of a study may be allowed; these instances should be discussed with the sponsor's medical monitor and written agreement obtained prior to enrollment.
• Current acute illness, with or without fever.
• Current or recent CHIKV infection indicated by positive immunoglobulin M (IgM) and negative immunoglobulin G (IgG) rapid diagnostic test (RDT) results at screening in the Philippines only; participants in the US will not be tested using the RDT.
• History of any known or suspected allergy or history of anaphylaxis to any component of the investigational product.
• History of any known congenital or acquired immunodeficiency or immunosuppressive condition that could impact response to vaccination.
• Prior receipt or anticipated use of systemic immunomodulatory or immunosuppressive medications from 180 days prior to screening through Day 22. Note: Systemic corticosteroid use at a dose or equivalent dose of 20 mg or greater (≥0.5 mg/kg for children \<40 kg) of prednisone for 14 consecutive days or more within 90 days of screening through Day 22 is exclusionary. The use of inhaled, intranasal, topical, or ocular steroids is allowed.
• Receipt or anticipated receipt of immunoglobulin from 180 days prior to screening through the duration of the study.
• Any administration or planned administration of: * A licensed live attenuated vaccine within 28 days before administration of investigational product and until Visit 2 (Day 15 or 22, as applicable) has occurred. * Other licensed (not live) vaccine within 14 days before administration of investigational product and until Visit 2 (Day 15 or 22, as applicable) has occurred. * Another licensed or investigational CHIKV vaccine.
• Known infection with human immunodeficiency virus, hepatitis C virus (HCV), or hepatitis B virus. Note: Positive anti-HCV antibodies and negative HCV polymerase chain reaction would NOT be exclusionary. Polymerase chain reaction testing will not be performed as part of this protocol.
• Bleeding disorder or receipt of anticoagulants in the 21 days before Day 1, contraindicating intramuscular vaccination, as judged by the investigator.
• Receipt or anticipated receipt of blood products from 90 days before Day 1 through the duration of the study.
• Onset of menarche prior to study vaccination.
• Planned medical or surgical procedure that could adversely impact the participant's participation or the conduct of the study.
• Identified as an immediate family member of the investigator or employee with direct involvement in the study. Bavarian Nordic staff members and their families, contractors, agents, business partners, and anyone with a financial interest in the outcome of the study.
• Any other medical condition, including severe malnutrition, that, in the opinion of the investigator, could adversely impact the participant's participation or conduct of the study.
BIOLOGICAL: CHIKV VLP vaccine, BIOLOGICAL: Placebo
Chikungunya Virus
Chikungunya, PXVX0317, CHIKV VLP, vaccine, immunogenicity, VIMKUNYA, children
Verifying Antibodies After Live Immunization Delivery (VALID): A Study of Measles Vaccine Immunogenicity in Children With Sickle Cell Disease (VALID)
MacKenzie Tasset - macKenzie.tasset@cchmc.org
ALL
6 months to 6 years old
NCT07356050
Inclusion Criteria:
• Participants with confirmed Sickle Cell Disease.
• Participants 6 months and 6 years of age and due for measles vaccination within 3 months per national guidelines.
• Willing and able to provide informed consent
• Ability to comply with study related evaluations and follow-up visits.
Exclusion Criteria:
1\. Known primary immunodeficiency syndrome, cancer, or acquired immunodeficiency syndrome (AIDS) that would preclude vaccination with live virus vaccines. Sickle Cell Disease, Measles Vaccination, Sickle Cell Anemia
Measles Vaccine Immunogenicity
Study to Learn About Safety, Tolerability, and Immune Response of a Catch-up Pneumococcal Vaccine in Children and Adolescents
- VaccineResearch@cchmc.org
ALL
15 months to 17 years old
PHASE3
NCT07660198
Inclusion Criteria:
Cohort 1 (Participants ≥15 Months to \<2 Years of Age) Healthy toddlers and children ≥15 months to \<2 years of age with documentation of prior receipt of PCV.
Cohort 2 (Participants ≥2 Years to \<5 Years of Age) Healthy toddlers and children ≥2 years to \<5 years of age with documentation of prior receipt of PCV if applicable.
Cohort 3 (Participants ≥5 Years to \<18 Years of Age) Healthy children ≥5 years to \<18 years of age with documentation of prior receipt of PCV (if applicable). A negative urine pregnancy test is required for individuals of childbearing potential (IOCBP). IOCBP or participants able to father must also agree to use a highly effective method of birth control.
Exclusion Criteria:
All Cohorts (Participants ≥15 Months to \<18 Years of Age)
Children with significant medical, psychiatric, or neurological conditions (eg, immunodeficiency or history of seizure); or a history of confirmed invasive pneumococcal infection in the past will be excluded from enrolment in the trial BIOLOGICAL: PG4, BIOLOGICAL: 20-valent pneumococcal conjugate vaccine (20vPnC)
Pneumococcal Disease
Targeted Reversal of Inflammation in Pediatric Sepsis-induced MODS (TRIPS)
Abigayle Gibson - abigayle.gibson@cchmc.org
ALL
1 day to 17 years old
PHASE2
NCT05267821
Inclusion Criteria:
* ≥ 40 weeks corrected gestational age to \< 18 years; AND
* Admission to the PICU or CICU; AND
* Onset of ≥ 2 new organ dysfunctions within the last 3 calendar days (compared to pre-sepsis baseline) as measured by the modified Proulx criteria; AND
* Documented or suspected infection as the MODS inciting event.
Exclusion Criteria:
* Weight \<3kg; OR
* Limitation of care order at the time of screening; OR
* Patients at high likelihood of progression to brain death in opinion of the clinical team; OR
* Moribund condition in which the patient is unlikely to survive the next 48 hours in opinion of the clinical team; OR
* Current or prior diagnosis of hemophagocytic lymphohistiocytosis or macrophage activation syndrome; OR
* Peripheral white blood cell count \< 1,000 cells/mm3 as the result of myeloablative therapy OR receipt of myeloablative therapy within the previous 14 days; OR
* Known allergy to anakinra, or E. coli-derived products; OR
* Known pregnancy; OR
* Lactating females; OR
* Receipt of anakinra within the previous 28 days; OR
* Resolution of MODS by MODS Day 2; OR
* Previous enrollment in the TRIPS study. DRUG: Anakinra, DRUG: Placebo
Pediatric Sepsis-induced Multiple Organ Dysfunction Syndrome (MODS)
A Study of Axatilimab at 3 Different Doses in Participants With Chronic Graft Versus Host Disease (cGVHD) (AGAVE-201)
Sara Loveless - sara.loveless@cchmc.org
ALL
2 years and over
PHASE2
NCT04710576
Inclusion Criteria:
• Participants must be 2 years of age or older, at the time of signing the informed consent.
• Participants who are allogeneic hematopoietic stem cell transplantation (HSCT) recipients with active cGVHD requiring systemic immune suppression. Active cGVHD is defined as the presence of signs and symptoms of cGVHD per 2014 NIH Consensus Development Project on Criteria for Clinical trials in cGVHD.
• Participants with refractory or recurrent active cGVHD despite at least 2 lines of systemic therapy. * Refractory disease defined as meeting any of the following criteria: * The development of 1 or more new sites of disease while being treated for cGVHD. * Progression of existing sites of disease despite at least 1 month of standard or investigation therapy for cGVHD. * Participants who have not achieved a response within 3 months on their prior therapy for cGVHD and for whom the treating physician believes a new systemic therapy is required. * Recurrent cGVHD is active, symptomatic disease (after an initial response to prior therapy) as defined, based on the NIH 2014 consensus criteria, by organ-specific or global assessment or for which the physician believes that a new line of systemic therapy is required.
• Participants may have persistent, active acute and cGVHD manifestations (overlap syndrome), as defined by 2014 NIH Consensus Development Project on Criteria for Clinical trials in cGVHD.
• Karnofsky Performance Scale of ≥60 (if aged 16 years or older); Lansky Performance Score of ≥60 (if aged \<16 years)
• Adequate organ and bone marrow functions evaluated during the 14 days prior to randomization.
• Creatinine clearance (CrCl) ≥30 milliliter/minute based on the Cockcroft-Gault formula in adult participants and Schwartz formula in pediatric participants.
• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Concomitant use a of systemic corticosteroid is allowed but not required. Topical and inhaled corticosteroid agents are allowed. If a participant is taking corticosteroids at study randomization, they must be on a stable dose of corticosteroids for at least 2 weeks prior to Cycle 1 Day 1.
• Concomitant use of CNI or mammalian target of repamycin (mTOR) inhibitors (sirolimus or everolimus) is allowed but not required.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol. A parent/guardian should provide consent for pediatric participants unable to provide consent themselves; in addition, where applicable pediatric participants should sign their own assent form.
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
• Has acute GVHD without manifestations of cGVHD.
• Any evidence (histologic, cytogenetic, molecular, hematologic, or mixed) of relapse of the underlying cancer or post-transplant lymphoproliferative disease at the time of screening.
• History of acute or chronic pancreatitis.
• History of myositis.
• History or other evidence of severe illness, uncontrolled infection or any other conditions that would make the participant, in the opinion of the Investigator, unsuitable for the study.
• Participants with acquired immune deficiency syndrome (AIDS).
• Hepatitis B (defined as hepatitis B virus \[HBV\] surface antigen positive and HBV core antibody positive, with positive HBV deoxyribonucleic acid \[DNA\], or HBV positive core antibody alone with positive HBV DNA. Hepatitis C (defined as positive hepatitis C \[HCV\] antibody with positive HCV ribonucleic acid \[RNA\]).
• Diagnosed with another malignancy (other than malignancy for which transplant was performed) within 3 years of randomization, unless previously treated with curative intent and approved by Sponsor's Medical Monitor (for example, completely resected basal cell or squamous cell carcinoma of the skin, resected in situ cervical malignancy, resected breast ductal carcinoma in situ, or low-risk prostate cancer after curative resection).
• Female participant who is pregnant or breastfeeding.
• Previous exposure to CSF1-R targeted therapies.
• Taking agents for treatment of cGVHD other than corticosteroids or either a CNI or mTOR inhibitor is prohibited.
• For approved or commonly used agents, other than corticosteroids, CNI and mTOR inhibitor, a washout of 2 weeks or 5 half-lives, whichever is shorter, is required at study enrollment.
• Receiving another investigational treatment within 28 days of randomization.
• Participants should not be participating in any other interventional study. Pediatric participants are encouraged to also participate in the ongoing developmental studies of the Pediatric cGVHD Symptom Scale (PCSS).
DRUG: Axatilimab
Chronic Graft-versus-host-disease
cGVHD, AGAVE-201, GVHD, graft versus host disease, graft-versus-host-disease