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

Lymphoblastic Leukemia, Acute Adult Clinical Trial

— TBI-1501  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03155191
• Other study ID #: 1501-01
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: June 1, 2017
• Est. completion date: March 31, 2035

Study information

• Verified date: November 2023
• Source: Takara Bio Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 21
• Est. completion date: March 31, 2035
• Est. primary completion date: March 31, 2035
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Lymphoblastic Leukemia, Acute Adult
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• 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.

Locations

Country	Name	City	State
Japan	Akita University Hospital	Akita
Japan	Kyushu University Hospital	Higashi-ku	Fukuoka
Japan	Kobe City Medical Center General Hospital	Kobe	Hyogo
Japan	Cancer Institute Hospital Of JFCR	Koto	Tokyo
Japan	The Institute of Medical Science, The University of Tokyo	Minato-ku	Tokyo
Japan	Okayama University Hospital	Okayama
Japan	Hokkaido University Hospital	Sapporo-shi	Hokkaido
Japan	Tohoku University Hospital	Sendai	Miyagi
Japan	Jichi Medical University hospital	Shimotsuke-shi	Tochigi
Japan	Mie University Hospital	Tsu-shi	Mie
Japan	University Of Fukui Hospital	Yoshida	Fukui

Sponsors (1)

Lead Sponsor	Collaborator
Takara Bio Inc.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase-I portion: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Adverse event (frequency, seriousness, duration, causality, severity, classification), mortality, severe adverse event, discontinuation due to adverse event.	One year
Primary	Phase-II portion: Anti-tumor effect (CR+CRi rate)	Complete Remission (CR)+Complete Remission with Incomplete Blood Count Recovery (CRi) , as determined by assessments of peripheral blood and bone marrow.	56 days