NCT03155191

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.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
21

participants targeted

Target at P25-P50 for phase_1

Timeline
108mo left

Started Jun 2017

Longer than P75 for phase_1

Geographic Reach
1 country

11 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress50%
Jun 2017Mar 2035

First Submitted

Initial submission to the registry

April 14, 2017

Completed
1 month until next milestone

First Posted

Study publicly available on registry

May 16, 2017

Completed
16 days until next milestone

Study Start

First participant enrolled

June 1, 2017

Completed
17.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 31, 2035

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 31, 2035

Last Updated

November 20, 2024

Status Verified

November 1, 2024

Enrollment Period

17.8 years

First QC Date

April 14, 2017

Last Update Submit

November 18, 2024

Conditions

Lymphoblastic Leukemia, Acute Adult

Keywords

Acute lymphoblastic leukemiaLeukemiaLymphoblasticTBI-1501Anti-CD19 CAR Expressing T cells TherapyCD19 CAR Gene-Transduced LymphocyteAdoptive ImmunotherapyGenetically Engineered Lymphocyte TherapyRetroviral VectorNeoplasms by Histologic TypeNeoplasmsNeoplasms, ExperimentalImmune System DiseasesChimeric antigen receptor

Outcome Measures

Primary Outcomes (2)

  • 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

Study Arms (1)

Dose Level -1 to 2

EXPERIMENTAL

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

Interventions

TBI-1501BIOLOGICAL

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.

Dose Level -1 to 2

Eligibility Criteria

Age16 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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).

You may not qualify if:

  • 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.
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

Akita University Hospital

Akita, Akita, 010-8543, Japan

Location

University Of Fukui Hospital

Yoshida, Fukui, 910-1193, Japan

Location

Kyushu University Hospital

Higashiku, Fukuoka, 812-8582, Japan

Location

Hokkaido University Hospital

Sapporo, Hokkaido, 060-8648, Japan

Location

Kobe City Medical Center General Hospital

Kobe, Hyōgo, 650-0047, Japan

Location

Mie University Hospital

Tsu, Mie-ken, 514-8507, Japan

Location

Tohoku University Hospital

Sendai, Miyagi, 980-8574, Japan

Location

Okayama University Hospital

Okayama, Okayama-ken, 700-8558, Japan

Location

Jichi Medical University hospital

Shimotsuke-shi, Tochigi, 329-0498, Japan

Location

Cancer Institute Hospital Of JFCR

Kōto, Tokyo, 135-8550, Japan

Location

The Institute of Medical Science, The University of Tokyo

Minato-ku, Tokyo, 108-8639, Japan

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-LymphomaLeukemiaNeoplasms by Histologic TypeNeoplasmsNeoplasms, ExperimentalImmune System Diseases

Condition Hierarchy (Ancestors)

Leukemia, LymphoidHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative Disorders

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Model Details: 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.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 14, 2017

First Posted

May 16, 2017

Study Start

June 1, 2017

Primary Completion (Estimated)

March 31, 2035

Study Completion (Estimated)

March 31, 2035

Last Updated

November 20, 2024

Record last verified: 2024-11

Data Sharing

IPD Sharing
Will not share

Locations

JP(11)