Overview

A study of CT-RD06 cell injection in patients with relapsed or refractory CD19+ B-cell hematological malignancy.

Eligibility

Inclusion Criteria:

• Inclusion criteria only for B-ALL:
  1. Male or female aged 3-70 years;
  2. Histologically confirmed diagnosis of CD19+ B-ALL per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Lymphoblastic Leukemia (2016.v1);
  3. Relapsed or refractory CD19+ B-ALL (meeting one of the following conditions):
  4. CR not achieved after standardized chemotherapy;
  5. CR achieved following the first induction, but CR duration is 12 months;
  6. Ineffectively after first or multiple remedial treatments;
  7. 2 or more relapses;
  8. The number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is5% (by morphology), and/or1% (by flow cytometry);
  9. Philadelphia-chromosome-negative (Ph-) patients; or Philadelphia-chromosome-positive (Ph+) patients who cannot tolerate TKI treatments or do not respond to 2 TKI treatments;
• Inclusion criteria only for B-NHL:
  1. Male or female aged 18-70 years;
  2. Histologically confirmed diagnosis of DLBCL (NOS), FL, DLBCL transformed from CLL/SLL, PMBCL, and HGBCL per the WHO Classification Criteria for Lymphoma (2016);
  3. Relapsed or refractory B-NHL (meeting one of the following conditions):
  4. No response or relapse after second-line or above chemotherapy regimens;
  5. Primary drug resistance;
  6. Relapse after auto-HSCT;
  7. At least one assessable tumor lesion per Lugano 2014 criteria;
• Common inclusion criteria for B-ALL and B-NHL:
  1. Total bilirubin 51 umol/L, ALT and AST 3 times of upper limit of normal, creatinine 176.8 umol/L;
  2. Echocardiogram shows left ventricular ejection fraction (LVEF) 50%;
  3. No active infection in the lungs, blood oxygen saturation in indoor air is 92%;
  4. Estimated survival time 3 months;
  5. ECOG performance status 0 to 2;
  6. Patients or their legal guardians volunteer to participate in the study and sign the informed consent.

Exclusion Criteria:

• Inclusion exclusion criteria only for B-ALL:
  1. Extramedullary lesions, except that CNSL (CNS-1) has been effectively controlled;
  2. Confirmed diagnosis of lymphoblastic crisis of chronic myeloid leukemia, Burkitt's leukemia/ lymphoma per WHO Classification Criteria;
  3. Hereditary syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome;
• Inclusion exclusion criteria only for B-NHL:
  1. Extranodal lesions in the brain (tumor cells in CSF, and/or MRI shows invasion of intracranial lymphoma);
  2. Extensive invasion of gastrointestinal lymphoma;
• Common exclusion criteria for B-ALL and B-NHL:
  1. History of hypersensitivity to any component of cell product;
  2. Prior treatment with any CAR T cell product or other genetically-modified T cell therapies;
  3. Prior treatment with radiotherapy, chemotherapy or mAb 1 week prior to apheresis;
  4. New York Heart Associate (NYHA) Class III/IV cardiac insufficiency (see Appendix 1);
  5. Myocardial infarction, cardioangioplasty or stenting, unstable angina pectoris, or other severe cardiac diseases within 12 months of enrollment;
  6. Severe primary or secondary hypertension of grade 3 or above (WHO Hypertension Guidelines, 1999);
  7. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
  8. History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases;
  9. Severe active infections (excluding simple urinary tract infection and bacterial pharyngitis);
  10. Indwelling catheters in vivo (e.g. percutaneous nephrostomy, Foley catheter, bile duct catheter, or pleural/peritoneal/pericardial catheter). Ommaya storage, dedicated central venous access catheters such as Port-a-Cath or Hickman catheters are allowed;
  11. History of other primary cancer, except for the following conditions:
  12. Cured non-melanoma after resection, such as basal cell carcinoma of the skin;
  13. Cervical cancer in situ, localized prostate cancer, ductal cancer in situ with disease-free survival 2 years after adequate treatment;
  14. Autoimmune diseases requiring treatment, immunodeficiency or patients requiring immunosuppressive therapy;
  15. Prior immunizations with live vaccine 4 weeks prior to screening;
  16. History of alcoholism, drug abuse or mental illness;
  17. If HBsAg positive at screening, HBV DNA copy number detected by PCR in patients with active hepatitis B > 1000 (if HBV DNA copy number1000, routine antiviral therapy is required after enrollment), as well as CMV, hepatitis C, syphilis and HIV infection;
  18. Concurrent therapy with systemic steroids within 1 week prior to screening, except for the patients recently or currently receiving inhaled steroids;
  19. Patients who have participated in any other clinical studies within 2 weeks prior to screening;
  20. Female pregnant or lactating, male for female fertile but unable to take medically acceptable contraception measures;
  21. Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.