Phase I Safety Clinical Trial of Anti-CD19 CAR-T Therapy COL01 for the Treatment of Adults With Relapsed or Refractory B-cell Lymphoid Neoplasms: First-in-human Administration, COLIBRI.

Prior treatment

• Prior Transplant: Autologous or allogeneic stem cell transplant less than 6 weeks prior to CAR-T cell infusion.
• Autoimmune Disease: History of autoimmune disease (e.g., systemic lupus erythematosus, rheumatoid arthritis) requiring immunosuppressive, immunomodulatory, or biological treatment, or having received such treatment within the last 6 months.
• Concurrent Investigational Agents: Simultaneous treatment with other investigational agents.
• Recent Radiotherapy: Radiotherapy within the last 14 days.
• Recent Major Surgery: Major surgery within the last 4 weeks prior to lymphodepletion.
• Hypersensitivity: History of hypersensitivity reactions to investigational products.
• Treatment Washout Non-compliance: Inability to comply with protocol-stipulated washout periods.

Other illness

• Active Infection: Active infection requiring systemic treatment.
• Active Second Malignancy Treatment: Active cancer treatment for a second primary malignancy.
• Prior Malignancies: History of cancer within the last two years prior to screening, except for appropriately locally treated malignancies considered in complete remission with minimal risk of requiring systemic therapy during the study (squamous or basal cell skin cancer, breast carcinoma, bladder carcinoma, cervical carcinoma in situ, low-grade prostate cancer Gleason \\\<= 6).
• CNS Malignancy: Known brain metastases or epidural disease of origin other than CD19+ malignancy.
• Active Infectious Diseases: Active infections including tuberculosis, active hepatitis B (positive viral load), hepatitis C (positive viral load), or HIV seropositivity.
• Cognitive / Psychiatric Conditions: Medical, psychiatric, or cognitive conditions that compromise the subject's capacity to understand information, make autonomous decisions, sign informed consent, or adhere to protocol requirements.
• Relevant CNS Pathologies: History of clinically relevant CNS pathologies (e.g., epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injury, dementia, or Parkinson's disease).
• \*\*Unstable CNS Disease:\*\* History of CNS

Lab values

• Severe Leukopenia: Leukopenia with white blood cell count \\\< 1.0 x 10\^9/L.
• Bilirubin Thresholds: Total bilirubin \\\> 2 mg/dL (except in patients with Gilbert's syndrome) or \\\> 1.5 mg/dL in patients with a history of hepatitis B or C.
• Transaminase Elevation \& Serology: Transaminase elevation \\\> 5 times the reference value, or \\\> 3 times in patients with a history of hepatitis B or C. Active or unresolved infection with Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or Human Immunodeficiency Virus (HIV).
• Uncontrolled Intercurrent Illness: Evidence of uncontrolled intercurrent illness, including but not limited to:
  • Active Cardiovascular Disease: Class III or IV congestive heart failure according to NYHA; unstable angina pectoris; severe cardiac arrhythmias.
  • Ischemic/Thromboembolic Events: Stroke (including transient ischemic attack , myocardial infarction, or thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism) within 3 months prior to the first dose.
  • ECG/Cardiac Parameters: QTc interval prolongation defined as QTcF \\\> 500 ms; known congenital long QT syndrome; Left Ventricular Ejection Fraction (LVEF) \\\< 45%.
  • Hypertension: Uncontrolled arterial hypertension (\\\>= 140/90 mmHg average of 3 measurements over 10 minutes despite \\\>= 2 antihypertensive drugs).
  • Metabolic / Renal: Poorly controlled diabetes mellitus despite adequate therapy; acute kidney disease requiring dialysis.
  • Other Safety Contraindications: Any condition that, in the principal investigator's judgment, contraindicates participation due to safety or protocol compliance concerns.

Other

• Pregnancy / Lactation: Pregnancy or breastfeeding. Females of childbearing potential must have a negative pregnancy test. If breastfeeding is discontinued, the patient will be considered for study participation.

• Age: Adults aged 18 years or older.
• Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status \\\<= 2.
• Life Expectancy: Expected life expectancy greater than 6 months.
• Informed Consent: Ability to sign the informed consent form.
• Organ Function: Adequate organ function defined as:
  • Hematologic: Absolute neutrophil count \\\>= 1,000/mm³, platelets \\\>= 50,000/mm³, hemoglobin \\\>= 8 g/dL.
  • Hepatic: Total bilirubin \\\<= 1.5 times the institutional upper limit of normal (ULN); AST/ALT \\\<= 2.5 x ULN.