Hemorrhagic Cystitis
Conditions
Keywords
BK-Virus, Hemorrhagic Cystitis, Virus-specific T cells, Allogeneic Hematopoietic Stem Cell Transplantation, Stem Cell Transplant, Virus Diseases, Infections, Cystitis
Brief summary
The goal of this clinical trial is to assess efficacy of BK virus specific T cells (LB-DTK-BKV) to treat pediatric, adolescent, and adult patients with BK virus-associated hemorrhagic cystitis after allogenic hematopoietic stem cell transplantation (allo-HSCT). It will also evaluate the safety of LB-DTK-BKV using treatment-emergent adverse events (TEAEs). The main questions it aims to answer are: * Does LB-DTK-BKV reduce the number of BKV virus viral load in allo-HSCT patients with hemorrhagic cystitis? * Do adverse events occur after the second dose? Researchers will compare LB-DTK-BKV to a placebo to see if LB-DTK-BKV works to treat hemorrhagic cystitis in allo-HSCT patients. Participants will: * Receive a single intravenous infusion of LB-DTK-BKV at the baseline visit (low dose: 1x10\^7/m\^2; high dose: 2x10\^7/m\^2). * Receive the second dose of LB-DTK-BKV intravenously at the same dose 14 days after the first dose. * Visit the clinic every week for follow-up for 6 months after the first dose.
Interventions
OTHERStandard-of-care
Standard-of-care therapy for BK virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation will be administered according to the participant's clinical status by the principal investigator. Participants in the placebo group will not receive LB-DTK-BKV during the clinical trial.
BIOLOGICALLB-DTK-BKV
LB-DTK-BKV derived from a designated donor determined based on the type of allogeneic hematopoietic stem cell transplant the subject is undergoing. A pale yellow cell suspension filled in a colorless, transparent freeze-dried vial that is stored frozen until thawed into liquid before administration. Study participants will receive a single intravenous infusion of the assigned cell dose (low dose: 1x10\^7/m\^2;high dose: 2x10\^7/m\^2) on Visit 2 and 14 days after the initial dose.
Sponsors
LucasBio
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients who have undergone allogeneic hematopoietic stem cell transplantation, including pediatric and adolescent patients as well as adults who were 12 years of age or older at the time of transplantation. However, only adults aged 19 years or older are eligible for enrollment in Phase 1. 2. Patients diagnosed with BK virus-associated hemorrhagic cystitis who meet all three of the following criteria. * Clinical symptoms and signs of cystitis, such as lower abdominal pain and dysuria * Hematuria of grade 2 or higher according to the Bedi criteria * Detection of BKV \>7log10 copies/mL in urine 3. Subjects confirmed by the investigator to be unresponsive to treatment despite at least 7 days of standard inpatient therapy. 4. Patients with evidence of neutrophil engraftment, defined as an absolute neutrophil count (ANC) maintained at 0.5 × 10³/μL or higher for 3 consecutive days following allogeneic hematopoietic stem cell transplantation. 5. Patients for whom at least 21 days (D+21) have elapsed since allogeneic hematopoietic stem cell transplantation as of the screening date. 6. Patients who are able to reduce their steroid dosage to 0.5 mg/kg/day of prednisolone (or an equivalent dose) or less. 7. For women of childbearing potential, those who tested negative on a pregnancy test (blood test) performed on the screening visit. 8. Female subjects or male subjects with female partners who agree to use the following contraceptive methods during the duration of this clinical trial and who meet the following criteria: * Female participants or male participants with female partners who are postmenopausal (diagnosed with non-therapy-induced amenorrhea for 12 months or more or menopause) * Female subjects or the female partners of male subjects who are surgically sterile (i.e., lacking ovaries and/or a uterus) * Individuals who have agreed to strict abstinence during the clinical trial period \[For female participants, intermittent abstinence (e.g., withdrawal during ovulation, the basal body temperature method, or withdrawal after ovulation) does not constitute agreement to abstinence\] * If the female subject or the female partner of a male subject is a woman of childbearing potential (WOCBP) who has not undergone sterilization, those who meet the following criteria: * Hormonal contraceptives (implant, patch, oral) * Intrauterine devices * Dual barrier method (simultaneous use of the following two contraceptive methods: male condoms, female condoms, cervical caps, contraceptive diaphragms, contraceptive sponges) 9. Individuals who have voluntarily decided to participate in this clinical trial and have provided written consent to comply with the restrictions. 10. Individuals deemed suitable as trial subjects through screening tests (vital signs, physical examination, medical and surgical history, electrocardiogram, laboratory tests, etc.).
Exclusion criteria
1. Individuals who have received treatment with ATG (Antithymocyte Globulin), Campath (Alemtuzumab), or other T-cell immunosuppressive monoclonal antibodies within 28 days prior to the first dose. 2. Patients with hemorrhagic cystitis caused by adenovirus (excluded via urine PCR) 3. Patients with bacterial growth in urine culture (excluded via bacterial culture) 4. Individuals who meet any of the following criteria at the time of screening: * Uncontrolled hypertension * Systolic BP ≥ 160 mmHg or diastolic BP ≥ 100 mmHg despite taking antihypertensive medication. * Uncontrolled diabetes: Severe diabetes is defined as follows. * Severe hyperglycemia with HbA1C ≥ 10.0% * Individuals who have been hospitalized for diabetic ketoacidosis within the past 12 weeks. * Individuals who have received emergency treatment or been hospitalized within the past 12 weeks for severe hypoglycemia (glucose \<54 mg/dL) accompanied by seizures and loss of consciousness. * Human Immunodeficiency Virus (HIV) infection * Hepatitis B Virus (HBV) infection. However, individuals who are HBsAg-negative and Anti-HBcAb-positive are not subject to this exclusion criterion. * Hepatitis C Virus (HCV) infection * Tuberculosis * Syphilis * Moderate or severe liver damage \[Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) \> 5 times the upper limit of normal (ULN)\] * Patients with other uncontrolled infections. However, the following cases are considered controlled infections and do not meet the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| BK virus viral load | From enrollment through 24 weeks after treatment initiation. | BK viral load testing is performed using RT-PCR on urine samples. Viral load is measured weekly for the first 4 weeks, followed by two measurements at 2-week intervals to monitor the progression of the infection, then once every 4 weeks, and subsequently once every 12 weeks. (That is, measurements are taken at weeks 1, 2, 3, 4, 6, 8, 12, and 24 after treatment initiation.) |
| Immunogenicity Testing | From enrollment through 24 weeks after treatment initiation. | Immunogenicity testing using the IFN-γ ELISpot assay is performed weekly for the first 4 weeks following administration of the investigational drug. Thereafter, to evaluate the persistence and reconstitution of the immune response, measurements are taken twice at 2-week intervals, once at 4-week intervals, and once at 12-week intervals. (i.e., measurements are taken at weeks 1, 2, 3, 4, 6, 8, 12, and 24 after dosing) |
| Adverse Events | From enrollment through 24 weeks after treatment initiation. | The investigator must confirm the occurrence of adverse events through medical examinations, including interviews and medical history reviews, during regular visits throughout the clinical trial period. Adverse events shall be assessed at each visit starting from the administration of the investigational drug at the baseline visit (Visit 2); however, from the baseline visit (Visit 2) until the discharge date, adverse events shall be assessed daily, and after the discharge date, assessments shall be conducted according to the procedures for each visit; diseases or symptoms that occurred prior to the first administration of the investigational drug shall be collected as part of the medical history. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| BK virus viral load | From enrollment through 24 weeks after treatment initiation. | BK viral load testing is performed using RT-PCR on blood samples. Viral load is measured weekly for the first 4 weeks, followed by two measurements at 2-week intervals to monitor the progression of the infection, then once every 4 weeks, and subsequently once every 12 weeks. (That is, measurements are taken at weeks 1, 2, 3, 4, 6, 8, 12, and 24 after treatment initiation.) |
Countries
South Korea
Contacts
CONTACTNayoun Kim, Ph.D.
PRINCIPAL_INVESTIGATORYae-Jean Kim, MD-PhD
Department of Pediatrics, Samsung Medical Center
PRINCIPAL_INVESTIGATORHyoung Jin Kang, MD-PhD
Department of Pediatric Hematology-Oncology, Seoul National University Hospital
PRINCIPAL_INVESTIGATORHo-joon Im, MD-PhD
Department of Pediatric Hematology & Oncology, Asan Medical Center
PRINCIPAL_INVESTIGATORHyeon Jin Park, MD-PhD
National Cancer Center, Korea
PRINCIPAL_INVESTIGATORSeung Min Hahn, MD-PhD
Department of Pediatric Hematology & Oncology, Severance Hospital
PRINCIPAL_INVESTIGATORHoon Kook, MD-PhD
Department of Pediatric Hematology & Oncology, Chonnam National University Hwasun Hospital
PRINCIPAL_INVESTIGATORJae-Cheol Jo, MD-PhD
Department of Hematology, Ulsan University Hospital
PRINCIPAL_INVESTIGATOREun Sun Yoo, MD-PhD
Department of Pediatric Hematology Oncology, Ewha Womans University Seoul Hospital
PRINCIPAL_INVESTIGATORJoonho Moon, MD-PhD
Department of Hematology-Oncology, Kyungpook National University Chilgok Hospital
Outcome results
None listed