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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Lymphoblastic Leukemia, Acute Adult
• Intervention / Treatment: Biological: TBI-1501

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.

• Study Type: Interventional
• Enrollment (Estimated): 21
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Japan
  • Akita, Japan, 010-8543
    • Akita University Hospital
  • Okayama, Japan, 700-8558
    • Okayama University Hospital
  • Fukui
    • Yoshida, Fukui, Japan, 910-1193
      • University of Fukui Hospital
  • Fukuoka
    • Higashi-ku, Fukuoka, Japan, 812-8582
      • Kyushu University Hospital
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital
  • Hyogo
    • Kobe, Hyogo, Japan, 650-0047
      • Kobe City Medical Center General Hospital
  • Mie
    • Tsu-shi, Mie, Japan, 514-8507
      • Mie University Hospital
  • Miyagi
    • Sendai, Miyagi, Japan, 980-8574
      • Tohoku University Hospital
  • Tochigi
    • Shimotsuke-shi, Tochigi, Japan, 329-0498
      • Jichi Medical University Hospital
  • Tokyo
    • Kōto, Tokyo, Japan, 135-8550
      • Cancer Institute Hospital of JFCR
    • Minato-ku, Tokyo, Japan, 108-8639
      • The Institute of Medical Science, The University of Tokyo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Takara Bio Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2017
• Primary Completion (Estimated): March 31, 2035
• Study Completion (Estimated): March 31, 2035

Study Registration Dates

• First Submitted: April 14, 2017
• First Submitted That Met QC Criteria: May 15, 2017
• First Posted (Actual): May 16, 2017

Study Record Updates

• Last Update Posted (Actual): November 20, 2024
• Last Update Submitted That Met QC Criteria: November 18, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Immune System Diseases; Neoplasms; Lymphoblastic; Leukemia; Adoptive Immunotherapy; Chimeric antigen receptor; Acute lymphoblastic leukemia; TBI-1501; Anti-CD19 CAR Expressing T cells Therapy; CD19 CAR Gene-Transduced Lymphocyte; Genetically Engineered Lymphocyte Therapy; Retroviral Vector; Neoplasms by Histologic Type; Neoplasms, Experimental
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia; Leukemia, Lymphoid; Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: 1501-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No