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

Primary Purpose

Lymphoblastic Leukemia, Acute Adult

Status
Active
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
TBI-1501
Sponsored by
Takara Bio Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoblastic Leukemia, Acute Adult focused on measuring Acute lymphoblastic leukemia, Leukemia, Lymphoblastic, TBI-1501, Anti-CD19 CAR Expressing T cells Therapy, CD19 CAR Gene-Transduced Lymphocyte, Adoptive Immunotherapy, Genetically Engineered Lymphocyte Therapy, Retroviral Vector, Neoplasms by Histologic Type, Neoplasms, Neoplasms, Experimental, Immune System Diseases, Chimeric antigen receptor

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University Of Fukui Hospital
  • Kyushu University Hospital
  • Hokkaido University Hospital
  • Kobe City Medical Center General Hospital
  • Mie University Hospital
  • Tohoku University Hospital
  • Jichi Medical University hospital
  • Cancer Institute Hospital Of JFCR
  • The Institute of Medical Science, The University of Tokyo
  • Akita University Hospital
  • Okayama University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dose Level -1 to 2

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Full Information

First Posted
April 14, 2017
Last Updated
June 15, 2022
Sponsor
Takara Bio Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03155191
Brief Title
Study of TBI-1501 for Relapsed or Refractory Acute Lymphoblastic Leukemia
Acronym
TBI-1501
Official Title
A Multicenter Phase I/II Study for Relapsed or Refractory CD19+ B-acute Lymphoblastic Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 1, 2017 (Actual)
Primary Completion Date
March 31, 2035 (Anticipated)
Study Completion Date
March 31, 2035 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takara Bio Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoblastic Leukemia, Acute Adult
Keywords
Acute lymphoblastic leukemia, Leukemia, Lymphoblastic, TBI-1501, Anti-CD19 CAR Expressing T cells Therapy, CD19 CAR Gene-Transduced Lymphocyte, Adoptive Immunotherapy, Genetically Engineered Lymphocyte Therapy, Retroviral Vector, Neoplasms by Histologic Type, Neoplasms, Neoplasms, Experimental, Immune System Diseases, Chimeric antigen receptor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Peripheral blood will be collected from a subject after obtaining a written informed consent. Peripheral blood mononuclear cells (PBMCs) and plasma are obtained from the blood, and T cells contained in the PBMCs are transduced with anti-CD19 CAR gene by using retroviral vector. Cyclophosphamide will be administered after obtaining a written informed consent and completing registration. CD19-CAR-T will be administered in the split dose. Phase 2 recommended dose will be applied for phase 1 portion. The investigator assesses efficacy of CD19-CAR-T in accordance with study-specific criteria, at 8 week after the infusion of CD19-CAR-T (or at the time of termination). The investigator also assesses the safety during the follow-up period. Long-term follow-up study is conducted at frequency of once a year for 15 years after the infusion of CD19-CAR-T in reference to guidelines of FDA.
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dose Level -1 to 2
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
TBI-1501
Intervention Description
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.
Primary Outcome Measure Information:
Title
Phase-I portion: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Description
Adverse event (frequency, seriousness, duration, causality, severity, classification), mortality, severe adverse event, discontinuation due to adverse event.
Time Frame
One year
Title
Phase-II portion: Anti-tumor effect (CR+CRi rate)
Description
Complete Remission (CR)+Complete Remission with Incomplete Blood Count Recovery (CRi) , as determined by assessments of peripheral blood and bone marrow.
Time Frame
56 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: In phase-1 study, patients must be ≥ 18 years of age. In phase-2 study, patients must be ≥ 16 years of age. Patients with relapse or refractory CD19+ acute B-cell lymphoblastic leukemia Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2. 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% 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: White blood cell counts ≧ 50,000/uL Received expected antitumor therapy (chemotherapy or radiation therapy, etc) within 2 weeks. Received HSCT within 12 weeks before enrollment. Under treatment for GVHD. lymphocytes except for blasts ≦ 500/uL Presence of active CNS-3 Concurrent use of systemic steroids or immunosuppressive agents (except for replacement therapy and local administration. e.g. inhalation, application and so on). HBs Ag positive ,or either HBc Ab positive or HBs positive with HBV-DNA > 1.3LogIU/ml Presence of active hepatitis C infection HIV Ab or anti-HTLV-1 Ab positive History of allergy about component of investigational product or animal(cattle and/or mouse)-derived additives Hypersensitivity to antibiotics. Presence of symptomatic cardiac arrhythmias or serious heart disease. Presence of another malignant tumor. Psychiatric disorder, alcohol addiction or drug addiction that affects the ability of informed consent. Active or serious infection. 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. Pregnant or lactating women. Any other patients judged by the investigators to be inappropriate for the study.
Facility Information:
Facility Name
University Of Fukui Hospital
City
Yoshida
State/Province
Fukui
ZIP/Postal Code
910-1193
Country
Japan
Facility Name
Kyushu University Hospital
City
Higashi-ku
State/Province
Fukuoka
ZIP/Postal Code
812-8582
Country
Japan
Facility Name
Hokkaido University Hospital
City
Sapporo-shi
State/Province
Hokkaido
ZIP/Postal Code
060-8648
Country
Japan
Facility Name
Kobe City Medical Center General Hospital
City
Kobe
State/Province
Hyogo
ZIP/Postal Code
650-0047
Country
Japan
Facility Name
Mie University Hospital
City
Tsu-shi
State/Province
Mie
ZIP/Postal Code
514-8507
Country
Japan
Facility Name
Tohoku University Hospital
City
Sendai
State/Province
Miyagi
ZIP/Postal Code
980-8574
Country
Japan
Facility Name
Jichi Medical University hospital
City
Shimotsuke-shi
State/Province
Tochigi
ZIP/Postal Code
329-0498
Country
Japan
Facility Name
Cancer Institute Hospital Of JFCR
City
Kōto
State/Province
Tokyo
ZIP/Postal Code
135-8550
Country
Japan
Facility Name
The Institute of Medical Science, The University of Tokyo
City
Minato-ku
State/Province
Tokyo
ZIP/Postal Code
108-8639
Country
Japan
Facility Name
Akita University Hospital
City
Akita
ZIP/Postal Code
010-8543
Country
Japan
Facility Name
Okayama University Hospital
City
Okayama
ZIP/Postal Code
700-8558
Country
Japan

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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