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

NCT ID: NCT03155191

Last Updated: 2024-11-20

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-01
• Study Completion Date: 2035-03-31

Brief Summary

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.

Detailed Description

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.

Conditions

Lymphoblastic Leukemia, Acute Adult

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose Level -1 to 2

0.3 to 3 x 10^6 autologous CD19-CAR-T cells/kg per patient will be administered intravenously after a conditioning chemotherapy with cyclophosphamide.

cohort -1: 3×10^5 cells/kg cohort 1: 1×10^6 cells/kg cohort 2: 3×10^6 cells/kg.

Group Type: EXPERIMENTAL

TBI-1501

Intervention Type: BIOLOGICAL

Phase-I portion:

Cyclophosphamide is administered for conditioning medication of TBI1501, that is CD19-CAR-T cells, (cohort -1: 3×10^5 cells/kg, cohort 1: 1×10^6 cells/kg, cohort 2: 3×10^6 cells/kg).

Phase-II portion:

Recommended dose of Phase-II part will be administered. Cyclophosphamide will be administered as conditioning. The end of study will be Week 52 after administration of TBI-1501.

Interventions

TBI-1501

Phase-I portion:

Cyclophosphamide is administered for conditioning medication of TBI1501, that is CD19-CAR-T cells, (cohort -1: 3×10^5 cells/kg, cohort 1: 1×10^6 cells/kg, cohort 2: 3×10^6 cells/kg).

Phase-II portion:

Recommended dose of Phase-II part will be administered. Cyclophosphamide will be administered as conditioning. The end of study will be Week 52 after administration of TBI-1501.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takara Bio Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Akita University Hospital

Akita, Akita, Japan

University Of Fukui Hospital

Yoshida, Fukui, Japan

Kyushu University Hospital

Higashiku, Fukuoka, Japan

Hokkaido University Hospital

Sapporo, Hokkaido, Japan

Kobe City Medical Center General Hospital

Kobe, Hyōgo, Japan

Mie University Hospital

Tsu, Mie-ken, Japan

Tohoku University Hospital

Sendai, Miyagi, Japan

Okayama University Hospital

Okayama, Okayama-ken, Japan

Jichi Medical University hospital

Shimotsuke-shi, Tochigi, Japan

Cancer Institute Hospital Of JFCR

Kōto, Tokyo, Japan

The Institute of Medical Science, The University of Tokyo

Minato-ku, Tokyo, Japan

Countries

Japan

Other Identifiers

1501-01

Identifier Type: -

Identifier Source: org_study_id