KSV01 Injection as the Therapy for Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia

Exclusion Criteria36

• Diagnosis of Burkitt's leukemia/lymphoma according to WHO 2016, or chronic myeloid leukemia in accelerated or blast phase.
• History of another primary malignancy that has not been in continuous remission for at least 2 years. Exceptions to the 2-year limit include: non-melanoma skin cancer, curatively treated Stage I solid tumor with low risk of recurrence, cured carcinoma in situ of the cervix (biopsy-confirmed) or squamous intraepithelial lesion on Pap smear, and cured localized prostate cancer.
• Uncontrolled active infection within 4 weeks prior to enrollment.
• Active hepatitis B or hepatitis C virus infection.
• HIV infection.
• Positive for Treponema pallidum(syphilis).
• Severe active autoimmune disease or immunodeficiency, with the exception of well-controlled Type I diabetes and thyroid disorders.
• History of severe allergy or hypersensitivity to macromolecular biological agents (e.g., antibodies, cytokines).
• Participation in another interventional clinical trial within 4 weeks prior to enrollment.
• History of clinically significant central nervous system (CNS) disorders, including but not limited to epilepsy, paresis, aphasia, stroke, severe head injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome.
• Central Nervous System (CNS) involvement:
• Presence of CNS 3 disease, defined as detectable blasts in the cerebrospinal fluid (CSF) with ≥5 WBCs/mm³, with or without neurological symptoms.
• Presence of CNS 2 disease, defined as detectable blasts in the CSF with \<5 WBCs/mm³ AND the presence of neurological symptoms.
• Note: Subjects with CNS 1 status (no detectable leukemic blasts in CSF) and subjects with CNS 2 status without significant clinical neurological abnormalities are eligible.
• History or presence of any CNS disorder, such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, any autoimmune disorder involving the CNS, posterior reversible encephalopathy syndrome, or cerebral edema.
• History of concomitant genetic syndromes associated with bone marrow failure, such as Fanconi anemia, Kostmann syndrome (severe congenital neutropenia), Shwachman-Diamond syndrome.
• History of any of the following cardiovascular conditions within the past 6 months: New York Heart Association (NYHA) Class III or IV heart failure, cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease.
• Active psychiatric illness.
• History of drug abuse/addiction.
• Use of the following medications or therapies:
• Salvage systemic therapy (including chemotherapy, TKIs for Ph+ ALL, and blinatumomab) within 1 week or 5 half-lives (whichever is shorter) prior to study drug infusion.
• Note:
• TKIs and hydroxyurea must be discontinued at least 72 hours prior to study drug infusion.\* 6-mercaptopurine, 6-thioguanine, methotrexate (standard dose), cytarabine (standard dose), vincristine, and asparaginase must be discontinued at least 1 week prior.\* Intrathecal chemotherapy for CNS prophylaxis must be discontinued at least 1 week prior.\* PEG-asparaginase must be discontinued at least 4 weeks prior.\*
• Prior anti-CD19 therapy other than blinatumomab.
• History of Grade 4 neurological toxicity (per CTCAE v5.0) or Grade 4 CRS (per Lee 2014 criteria) during prior blinatumomab treatment.
• Prior treatment with alemtuzumab within 6 months, or with clofarabine or cladribine within 3 months prior to study drug infusion.
• Systemic treatment for Graft-versus-Host Disease (e.g., calcineurin inhibitors, methotrexate, mycophenolate mofetil, sirolimus, thalidomide) or immunosuppressive antibody therapy (e.g., anti-CD20, anti-TNF, anti-IL-6, or anti-IL-6R antibodies) within 4 weeks prior to enrollment.
• Any prior systemic therapy with inhibitory/stimulatory immune checkpoint molecules (e.g., ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists). A washout period of at least 3 half-lives from the last dose is required before enrollment.
• Radiotherapy: Non-CNS directed radiotherapy within 2 weeks or CNS-directed radiotherapy within 8 weeks prior to study drug infusion.
• Corticosteroids: Therapeutic doses of corticosteroids (defined as prednisone equivalent \>20 mg/day) within 72 hours prior to study drug infusion. Physiologic replacement doses, and topical or inhaled steroids are permitted.
• Prior gene therapy.
• Prior adoptive cell therapy.
• Acute Graft-versus-Host Disease (GVHD) of Grade II to IV per Glucksberg criteria, or overall grade B-D per the IBMTR Severity Index; OR acute or chronic GVHD requiring systemic therapy within 4 weeks prior to enrollment.
• Administration of a live vaccine within 4 weeks prior to enrollment.
• Pregnancy or lactation.
• Any condition that, in the investigator's judgment, may compromise the subject's ability to complete all required study visits and procedures (including follow-up), or comply with the study requirements.