A Study of CT-RD06 Cell Injection in Patients With Relapsed or Refractory CD19+ B-cell Hematological Malignancy

A Study of CT-RD06 Cell Injection in Patients With Relapsed or Refractory CD19+ B-cell Hematological Malignancy

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

This is a single arm, open-label, single-center study. This study is indicated for relapsed or refractory CD19+ B-cell hematological malignancy: B-ALL and B-NHL, the selections of dose levels and the number of subjects are based on clinical trials of similar foreign products. 2 groups of patients will be enrolled, 36 in each group. Primary objective is to explore the safety, main consideration is dose-related safety.

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):

     1. CR not achieved after standardized chemotherapy;
     2. CR achieved following the first induction, but CR duration is ≤ 12 months;
     3. Ineffectively after first or multiple remedial treatments;
     4. 2 or more relapses;

  4. The number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is﹥5% (by morphology), and/or﹥1% (by flow cytometry);

  5. 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):

     1. No response or relapse after second-line or above chemotherapy regimens;
     2. Primary drug resistance;
     3. Relapse after auto-HSCT;

  4. 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:

      1. Cured non-melanoma after resection, such as basal cell carcinoma of the skin;
      2. Cervical cancer in situ, localized prostate cancer, ductal cancer in situ with disease-free survival ≥ 2 years after adequate treatment;

  12. Autoimmune diseases requiring treatment, immunodeficiency or patients requiring immunosuppressive therapy;

  13. Prior immunizations with live vaccine 4 weeks prior to screening;

  14. History of alcoholism, drug abuse or mental illness;

  15. If HBsAg positive at screening, HBV DNA copy number detected by PCR in patients with active hepatitis B > 1000 (if HBV DNA copy number≤1000, routine antiviral therapy is required after enrollment), as well as CMV, hepatitis C, syphilis and HIV infection;

  16. Concurrent therapy with systemic steroids within 1 week prior to screening, except for the patients recently or currently receiving inhaled steroids;

  17. Patients who have participated in any other clinical studies within 2 weeks prior to screening;

  18. Female pregnant or lactating, male for female fertile but unable to take medically acceptable contraception measures;

  19. Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.