Lymphoblastic Leukemia, Acute AdultPhase 1/2TBI-1501NCT03155191
Study of TBI-1501 for Relapsed or Refractory Acute Lymphoblastic Leukemia
A Phase 1/2 study testing TBI-1501 in people with Lymphoblastic Leukemia, Acute Adult, run by Takara Bio Inc. at 11 sites in Japan.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Lymphoblastic Leukemia, Acute Adult
- What is being tested?
- TBI-1501
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 11 sitesJapan
- Study dates
- 1 Jun 2017to 31 Mar 2035
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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).
Who cannot join
- 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
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- 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.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
Japan11 sites
Akita University Hospital
Akita, Akita, 010-8543
Kyushu University Hospital
Higashiku, Fukuoka, 812-8582
Kobe City Medical Center General Hospital
Kobe, Hyōgo, 650-0047
Cancer Institute Hospital Of JFCR
Kōto, Tokyo, 135-8550
The Institute of Medical Science, The University of Tokyo
Minato-ku, Tokyo, 108-8639
Okayama University Hospital
Okayama, Okayama-ken, 700-8558
Hokkaido University Hospital
Sapporo, Hokkaido, 060-8648
Tohoku University Hospital
Sendai, Miyagi, 980-8574
Jichi Medical University hospital
Shimotsuke-shi, Tochigi, 329-0498
Mie University Hospital
Tsu, Mie-ken, 514-8507
University Of Fukui Hospital
Yoshida, Fukui, 910-1193
About this study
Official title: 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.
Read the 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.
- Conditions
- Lymphoblastic Leukemia, Acute Adult
- Being tested
- TBI-1501
- 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
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Neoplasms by Histologic Type, Neoplasms, Neoplasms, Experimental, Immune System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: TBI-1501 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 56 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2017
- Study start1 Jun 2017
- Primary completion31 Mar 2035 (estimated)
- Study completion31 Mar 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lymphoblastic Leukemia, Acute AdultStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 21 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Takara Bio Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03155191
- Sponsor's protocol ID
- 1501-01
- Acronym
- TBI-1501
- Status last verified
- Nov 2024
- First submitted
- 14 Apr 2017
- Last updated
- 20 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Phase I/II Study for Relapsed or Refractory CD19+ B-acute Lymphoblastic Leukemia
- ClinicalTrials.gov ID
- NCT03155191
- Acronym / sponsor ID
- TBI-1501 / 1501-01
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 21 participants (estimated)
- Lead sponsor
- Takara Bio Inc.Industry (pharma, biotech, devices)
- Study start
- 1 Jun 2017 (actual)
- Primary completion
- 31 Mar 2035 (estimated)
- Study completion
- 31 Mar 2035 (estimated)
- First posted
- 16 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| Dose Level -1 to 2 | Experimental | Biological: TBI-15010.3 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. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- 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
- 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).
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TBI-1501Phase-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. | Biological | Dose Level -1 to 2 |
Primary outcome
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.
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing TBI-1501 in people with Lymphoblastic Leukemia, Acute Adult, run by Takara Bio Inc. at 11 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 20 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase-I portion: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (time frame: One year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2024.