Clinical trial NCT03155191: Study of TBI-1501 for Relapsed or Refractory Acute Lymphoblastic Leukemia
Official title: A Multicenter Phase I/II Study for Relapsed or Refractory CD19+ B-acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: 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
Lead sponsor: Takara Bio Inc.
Sponsor class: INDUSTRY
First posted: 2017-05-16
Enrollment: 21
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Phase-I portion: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: One year
measure: Phase-II portion: Anti-tumor effect (CR+CRi rate)
timeFrame: 56 days
Secondary outcomes:
Other outcomes:
Locations:
city: Yoshida
country: Japan
facility: University Of Fukui Hospital
state: Fukui
city: Higashi-ku
country: Japan
facility: Kyushu University Hospital
state: Fukuoka
city: Sapporo-shi
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Kobe
country: Japan
facility: Kobe City Medical Center General Hospital
state: Hyogo
city: Tsu-shi
country: Japan
facility: Mie University Hospital
state: Mie
city: Sendai
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Shimotsuke-shi
country: Japan
facility: Jichi Medical University hospital
state: Tochigi
city: Kōto
country: Japan
facility: Cancer Institute Hospital Of JFCR
state: Tokyo
city: Minato-ku
country: Japan
facility: The Institute of Medical Science, The University of Tokyo
state: Tokyo
city: Akita
country: Japan
facility: Akita University Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
Study officials:
References: