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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03155191
Recruitment Status : Recruiting
First Posted : May 16, 2017
Last Update Posted : February 15, 2019
Sponsor:
Information provided by (Responsible Party):
Takara Bio Inc.

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.

Condition or disease Intervention/treatment Phase
Lymphoblastic Leukemia, Acute Adult Biological: TBI-1501 Phase 1 Phase 2

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.

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Study Type : Interventional
Estimated Enrollment : 21 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention 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)
Primary Purpose: Treatment
Official Title: A Multicenter Phase I/II Study for Relapsed or Refractory CD19+ B-acute Lymphoblastic Leukemia
Actual Study Start Date : June 1, 2017
Estimated Primary Completion Date : March 31, 2019
Estimated Study Completion Date : March 31, 2020


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.





Primary Outcome Measures :
  1. Phase-I portion: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: One year ]
    Adverse event (frequency, seriousness, duration, causality, severity, classification), mortality, severe adverse event, discontinuation due to adverse event.

  2. Phase-II portion: Anti-tumor effect (CR+CRi rate) [ Time Frame: 56 days ]
    Complete Remission (CR)+Complete Remission with Incomplete Blood Count Recovery (CRi) , as determined by assessments of peripheral blood and bone marrow.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03155191


Contacts
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Contact: Takara Bio Inc. +81-77-565-6970 takara-clinical@takara-bio.co.jp

Locations
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Japan
Kyushu University Hospital Recruiting
Higashi-ku, Fukuoka, Japan, 812-8582
Hokkaido University Hospital Recruiting
Sapporo-shi, Hokkaido, Japan, 060-8648
Mie University Hospital Recruiting
Tsu-shi, Mie, Japan, 514-8507
Tohoku University Hospital Recruiting
Sendai, Miyagi, Japan, 980-8574
Jichi Medical University hospital Recruiting
Shimotsuke-shi, Tochigi, Japan, 329-0498
The Institute of Medical Science, The University of Tokyo Recruiting
Minato-ku, Tokyo, Japan, 108-8639
Sponsors and Collaborators
Takara Bio Inc.
Investigators
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Study Director: Masanobu Kimura Takara Bio Inc.
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Responsible Party: Takara Bio Inc.
ClinicalTrials.gov Identifier: NCT03155191    
Other Study ID Numbers: 1501-01
First Posted: May 16, 2017    Key Record Dates
Last Update Posted: February 15, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Takara Bio Inc.:
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Experimental
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
Immune System Diseases
Chimeric antigen receptor
Additional relevant MeSH terms:
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Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases