Study of TBI-1501 for Relapsed or Refractory Acute Lymphoblastic Leukemia

A Multicenter Phase I/II Study for Relapsed or Refractory CD19+ B-acute Lymphoblastic Leukemia

Evaluate the safety (P-I), pharmacokinetics and anti-tumor effect of immunotherapy of autologous T cells genetically modified to express anti-CD19 chimeric antigen receptor (CAR) (TBI-1501) for relapsed or refractory CD19+ B-cell acute lymphoblastic leukemia.

Enroll patients after confirming eligibility. Following enrollment, peripheral blood mononuclear cells and blood plasma will be obtained from each subject by apheresis to start the manufacturing of TBI-1501.

Before TBI-1501 administration, it is necessary to pass the quality tests. Subject will be hospitalized from Day -3 to Day 28, and administered Cyclophosphamide (1,000 mg/m2/day×2 days) on Day -3 and Day -2.

Inclusion Criteria:

1. In phase-1 study, patients must be ≥ 18 years of age. In phase-2 study, patients must be ≥ 16 years of age.

2. Patients with relapse or refractory CD19+ acute B-cell lymphoblastic leukemia

3. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.

4. Patients must have adequate key organ function (bone marrow, heart, lung, liver, renal, etc), as defined below

   • Total bilirubin level ≤1.5xULN (Upper limit of normal)
   • AST(GOT)/ALT(GPT) level ≤5.0xULN
   • Serum creatinine ≤2.0mg/dL
   • SpO2 ≧ 92%
   • LVEF ≥50%

5. Patients must be able to understand and willing to sign a written informed consent document (for patients <20 years of age their legal guardian must give informed consent).

Exclusion Criteria:

1. White blood cell counts ≧ 50,000/uL
2. Received expected antitumor therapy (chemotherapy or radiation therapy, etc) within 2 weeks.
3. Received HSCT within 12 weeks before enrollment.
4. Under treatment for GVHD.
5. lymphocytes except for blasts ≦ 500/uL
6. Presence of active CNS-3
7. Concurrent use of systemic steroids or immunosuppressive agents (except for replacement therapy and local administration. e.g. inhalation, application and so on).
8. HBs Ag positive ,or either HBc Ab positive or HBs positive with HBV-DNA > 1.3LogIU/ml
9. Presence of active hepatitis C infection
10. HIV Ab or anti-HTLV-1 Ab positive
11. History of allergy about component of investigational product or animal(cattle and/or mouse)-derived additives
12. Hypersensitivity to antibiotics.
13. Presence of symptomatic cardiac arrhythmias or serious heart disease.
14. Presence of another malignant tumor.
15. Psychiatric disorder, alcohol addiction or drug addiction that affects the ability of informed consent.
16. Active or serious infection.
17. Both men and women who have generative functions, and who cannot agree with using contraceptive devices from the day of the consent to the end of study.
18. Pregnant or lactating women.
19. Any other patients judged by the investigators to be inappropriate for the study.