Acute Lymphocytic LeukemiaPhase 1NCT05727683
CD19-targeted CAR T Cells for Patients With Relapsed or Refractory in B-cell Acute Lymphoblastic Leukemia
A Phase 1 study testing CD19-targeted Chimeric Antigen Receptor (CAR) T Cells in people with Acute Lymphocytic Leukemia, run by Shanghai Ming Ju Biotechnology Co., Ltd. at 1 site in China.
Trial summary
This is a phase I, open-label, single-arm study conducted in China to evaluate the safety, tolerability, PK, and determine the recommended phase II dose (RP2D) and/or maximum tolerated dose (MTD) (if applicable) of JWCAR029 in pediatric and young adult subjects with r/r B-ALL. Read more about this study
- Who is it for?
- Ages Up to 30 years
- Conditions the study is for
- Acute Lymphocytic Leukemia
- What is being tested?
- CD19-targeted Chimeric Antigen Receptor (CAR) T Cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteChina
- Study dates
- 28 Apr 2022to 31 Jul 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 Up to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age ≤ 30 years and weight ≥10kg.
- Patients with r/r B-ALL, defined as morphological disease in the bone marrow(≥5% blasts) and either of the following:
- ≥2 BM relapse;
- Refractory defined as relapse if first remission<12 months or not achieving a CR after 1 cycle of a standard induction chemotherapy regimen for relapsed leukemia;primary chemo-refractory as defined by not achieving a CR after 1 cycle of a conventional chemotherapy or 2 cycles of a standard induction chemotherapy regimen for relapsed leukemia;
- Any BM relapse after HSCT which must be ≥90 days from HSCT at the time of screening, and be required free from GVHD and ended from any immunosuppressive therapy ≥1 month at the time of screening;
- Patients with Ph+ ALL are eligible if they are intolerant to or have failed two lines of TKI therapy, or if TKI therapy is contraindicated.
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- Note: Patients with MRD+ after bridging therapy will be allowed for treatment.
- Karnofsky (age ≥16 years) or Lansky (age <16 years) performance status >60.
- Adequate organ function.
- Vascular access is sufficient for leukocyte isolation.
- Expected survival time > 3 months.
- Any non-hematological toxicity due to previous treatment, except for alopecia and peripheral neuropathy, must be restored to ≤ grade 1.
- Females of childbearing potential (all female subjects who are physiologically capable of becoming pregnant) must agree to use a highly effective method of contraception for 1 year following JWCAR029 infusion; male subjects whose partners are of childbearing potential must agree to use an effective barrier method of contraception for 1 year following JWCAR029 infusion.
Who cannot join
- leukemic CNS involvement with active CNS lesions and significant neurodegenerative manifestations, or subjects with CNS grade CNS-2/CNS-3 as assessed by NCCN guidelines (subjects rated CNS-2 due to puncture injury may be enrolled).
- existing or previous clinically significant CNS lesions such as epilepsy, epileptic seizures, paralysis, aphasia, cerebral edema, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis, etc.
- Patients with genetic syndromes other than Down syndrome.
- Patients with Burkitt's lymphoma.
- History of malignancy other than B-ALL for at least 2 years prior to enrollment.
- Subject has HBV, HCV, HIV or syphilis infection at the time of screening.
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- Subject has deep vein thrombosis (DVT) (cancer thrombosis or thrombosis) or pulmonary artery embolism (PE) or is on anticoagulation therapy for DVT or PE within 3 months prior to signing the informed consent form
- uncontrolled systemic fungal, bacterial, viral or other infections.
- Combination of active autoimmune diseases requiring immunosuppressive therapy.
- Acute or chronic graft-versus-host disease.
- History of any of the following cardiovascular diseases within the past 6 months: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant heart disease.
- Women who are pregnant or lactating. Women of childbearing potential must have a negative serum pregnancy test within 48 hours prior to initiation of lymphocyte clearance chemotherapy.
- Previous treatment with CAR-T cells or other gene-modified T cells.
- Previous anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy.
- Relevant medications or treatments within a specified time frame.
- The presence of any factors affecting the subject's compliance with the protocol, including uncontrollable medical, psychological, family, sociological, or geographic conditions, as determined by the investigator; or unwillingness or inability to comply with the procedures required in the study protocol.
- Known life-threatening allergic reactions, hypersensitivity reactions, or intolerance to JWCAR029 cell formulation or its excipients.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Hematology Hospital, Chinese Academy of Medical Sciences
Tianjin, Tianjin Municipality, 300020
Xiaofan Zhu, PhD, 13752090418, xfzhu@ihcams.ac.cn
About this study
Official title: A Phase I Open, Single-arm Study of JWCAR029 (CD19-targeted Chimeric Antigen Receptor T Cells) for Patients With Relapsed or Refractory in B-cell Acute Lymphoblastic Leukemia
This is a phase I, open-label, single-arm study conducted in China to evaluate the safety, tolerability, PK, and determine the recommended phase II dose (RP2D) and/or maximum tolerated dose (MTD) (if applicable) of JWCAR029 in pediatric and young adult subjects with r/r B-ALL.
Read the detailed description
Dose exploration for this study will be a 3+3 design with a target DLT rate of <1/3. Dose exploration can be discontinued once one or more dose levels with an acceptable safety profile and satisfactory antitumor activity have been selected for subsequent evaluation. The maximum tolerated dose (MTD) may not be achieved at the dose levels predetermined in this study as described below.
During the treatment period of the study, four dose levels of JWCAR029 will be evaluated. enrollment will begin at dose level 1, follow a 3+3 dose exploration design protocol, and finally select one or more dose levels with an acceptable safety profile and good antitumor activity as the recommended dose, after which dose exploration will be discontinued.
Dose limiting toxicity (DLT) will be evaluated within 28 days after JWCAR029 infusion. Each dose cohort is planned to enroll three subjects initially, and at least one pediatric subject younger than 10 years of age who can be evaluated for DLT will be enrolled at each dose level. In the first dose cohort, the first 3 subjects will be infused at least 14 days apart. At each higher dose level, the first 3 patients within the dose cohort will be treated at least 7 days apart. For dose levels considered safe, at least 3 subjects with assessable DLT must complete a 28-day DLT assessment period.
- Conditions
- Acute Lymphocytic Leukemia
- Being tested
- CD19-targeted Chimeric Antigen Receptor (CAR) T Cells
- Keywords
- JWCAR029, Relapsed/Refractory, Pediatric and young adults
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD19-targeted Chimeric Antigen Receptor (CAR) T CellsBiological
Also called Fludarabine, Cyclophosphamide
Subjects will receive Lymphodepleting chemotherapy with intravenous (IV) fludarabine (25 mg/m2/day for 3 days) plus cyclophosphamide IV (250 mg/m2/day for 3 days) (flu/cy) concurrently, followed by JWCAR029 cells infusion. Phase 1 will evaluate up to 4 JWCAR029 cells dose levels.
| Study group | Role | What they receive |
|---|---|---|
| JWCAR029 Treatment | Experimental | A lymphodepletion conditioning with cyclophosphamide and fludarabine will be conducted before JWCAR029 infusion.
Potential JWCAR029 doses:
Dose level 1: 0.10×10^6 CAR+ T cells/kg Dose level 2: 0.30×10^6 CAR+ T cells/kg Dose level 3: 0.75×10^6 CAR+ T cells/kg Dose level 4: 1.0×10^6 CAR+ T cells/kg Receives: Biological: CD19-targeted Chimeric Antigen Receptor (CAR) T Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)
Dose limiting toxicity (DLT) is an AE that meets the following criteria and occurs within 28 days of JWCAR029 infusion.AE is graded according to CTCAE version 5.0, CRS is graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) 2019 consensus CRS grading criteria, and neurotoxicity is graded according to the ASTCT 2019 consensus ICANS grading criteria.
Measured: Day 28 after JWCAR029 infusion
The occurrence of adverse events
These adverse events would be measured by assessment scale method according to NCI CTC AE v5.0 classification standard
Measured: After JWCAR029 infusion for 2 year
Secondary outcomes (2)
Overall remission Rate
Overall remission rates assessed by investigators at 1, 2, and 3 months after JWCAR029 infusion,Include complete remission (CR) and complete morphological remission without complete recovery of blood counts （CRi），and the results of the efficacy assessment at each time point
Measured: After JWCAR029 infusion for 2 year
MRD negative rate
Investigator assessed response rate for microscopic residual disease (MRD) at 1 , 2 and 3 months after completion of infusion, including the percentage of patients achieving MRD negativity (MRD level <10^-4) among all infused patients
Measured: After JWCAR029 infusion for 2 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Feb 2023
- Study start28 Apr 2022
- Primary completion31 Oct 2023 (estimated)
- Study completion31 Jul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphocytic LeukemiaStudies 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Ming Ju Biotechnology Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Xiaofan Zhu, PhD, Principal investigator, Hematology Hospital, Chinese Academy of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05727683
- Sponsor's protocol ID
- JWCAR029-006
- Status last verified
- Feb 2023
- First submitted
- 5 Feb 2023
- Last updated
- 14 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- 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 14 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Open, Single-arm Study of JWCAR029 (CD19-targeted Chimeric Antigen Receptor T Cells) for Patients With Relapsed or Refractory in B-cell Acute Lymphoblastic Leukemia
- ClinicalTrials.gov ID
- NCT05727683
- Acronym / sponsor ID
- JWCAR029-006
- Conditions
- Acute Lymphocytic Leukemia
- Keywords
- JWCAR029, Relapsed/Refractory, Pediatric and young adults
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 33 participants (estimated)
- Lead sponsor
- Shanghai Ming Ju Biotechnology Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 28 Apr 2022 (actual)
- Primary completion
- 31 Oct 2023 (estimated)
- Study completion
- 31 Jul 2025 (estimated)
- First posted
- 14 Feb 2023 (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.
This is a phase I, open-label, single-arm study conducted in China to evaluate the safety, tolerability, PK, and determine the recommended phase II dose (RP2D) and/or maximum tolerated dose (MTD) (if applicable) of JWCAR029 in pediatric and young adult subjects with r/r B-ALL.
Detailed description
Dose exploration for this study will be a 3+3 design with a target DLT rate of <1/3. Dose exploration can be discontinued once one or more dose levels with an acceptable safety profile and satisfactory antitumor activity have been selected for subsequent evaluation. The maximum tolerated dose (MTD) may not be achieved at the dose levels predetermined in this study as described below.
During the treatment period of the study, four dose levels of JWCAR029 will be evaluated. enrollment will begin at dose level 1, follow a 3+3 dose exploration design protocol, and finally select one or more dose levels with an acceptable safety profile and good antitumor activity as the recommended dose, after which dose exploration will be discontinued.
Dose limiting toxicity (DLT) will be evaluated within 28 days after JWCAR029 infusion. Each dose cohort is planned to enroll three subjects initially, and at least one pediatric subject younger than 10 years of age who can be evaluated for DLT will be enrolled at each dose level. In the first dose cohort, the first 3 subjects will be infused at least 14 days apart. At each higher dose level, the first 3 patients within the dose cohort will be treated at least 7 days apart. For dose levels considered safe, at least 3 subjects with assessable DLT must complete a 28-day DLT assessment period.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| JWCAR029 Treatment | Experimental | Biological: CD19-targeted Chimeric Antigen Receptor (CAR) T CellsA lymphodepletion conditioning with cyclophosphamide and fludarabine will be conducted before JWCAR029 infusion. Potential JWCAR029 doses: Dose level 1: 0.10×10^6 CAR+ T cells/kg Dose level 2: 0.30×10^6 CAR+ T cells/kg Dose level 3: 0.75×10^6 CAR+ T cells/kg Dose level 4: 1.0×10^6 CAR+ T cells/kg |
Who may qualify
- Ages
- Up to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (13 listed)
- Age ≤ 30 years and weight ≥10kg.
- Patients with r/r B-ALL, defined as morphological disease in the bone marrow(≥5% blasts) and either of the following:
- Note: Patients with MRD+ after bridging therapy will be allowed for treatment.
- Karnofsky (age ≥16 years) or Lansky (age <16 years) performance status >60.
- Adequate organ function.
Key exclusion criteria (17 listed)
- leukemic CNS involvement with active CNS lesions and significant neurodegenerative manifestations, or subjects with CNS grade CNS-2/CNS-3 as assessed by NCCN guidelines (subjects rated CNS-2 due to puncture injury may be enrolled).
- existing or previous clinically significant CNS lesions such as epilepsy, epileptic seizures, paralysis, aphasia, cerebral edema, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis, etc.
- Patients with genetic syndromes other than Down syndrome.
- Patients with Burkitt's lymphoma.
- History of malignancy other than B-ALL for at least 2 years prior to enrollment.
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 |
|---|---|---|
| CD19-targeted Chimeric Antigen Receptor (CAR) T CellsAlso: Fludarabine, CyclophosphamideSubjects will receive Lymphodepleting chemotherapy with intravenous (IV) fludarabine (25 mg/m2/day for 3 days) plus cyclophosphamide IV (250 mg/m2/day for 3 days) (flu/cy) concurrently, followed by JWCAR029 cells infusion. Phase 1 will evaluate up to 4 JWCAR029 cells dose levels. | Biological | JWCAR029 Treatment |
Primary outcome
Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)
Time frame: Day 28 after JWCAR029 infusion
Dose limiting toxicity (DLT) is an AE that meets the following criteria and occurs within 28 days of JWCAR029 infusion.AE is graded according to CTCAE version 5.0, CRS is graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) 2019 consensus CRS grading criteria, and neurotoxicity is graded according to the ASTCT 2019 consensus ICANS grading criteria.
The occurrence of adverse events
Time frame: After JWCAR029 infusion for 2 year
These adverse events would be measured by assessment scale method according to NCI CTC AE v5.0 classification standard
2 secondary outcomes
Overall remission Rate
Time frame: After JWCAR029 infusion for 2 year
MRD negative rate
Time frame: After JWCAR029 infusion for 2 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Feb 2023.
- 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.
Xiaofan Zhu, PhD principal investigator
Hematology Hospital, Chinese Academy of Medical Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CD19-targeted Chimeric Antigen Receptor (CAR) T Cells in people with Acute Lymphocytic Leukemia, run by Shanghai Ming Ju Biotechnology Co., Ltd. at 1 site in China.
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 13 inclusion and 17 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: status not confirmed, as of the sponsor's last update on 14 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Xiaofan Zhu, PhD (+86 13752090418, xfzhu@ihcams.ac.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) (time frame: Day 28 after JWCAR029 infusion). 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 14 Feb 2023.