Acute Lymphocytic LeukemiaPhase 1/2NCT07008885
BCOR and ZC3H12 Genes Knock-out CD19-targeting CAR-T Cell Therapy in r/r B-ALL
A Phase 1/2 study testing CAR19TIF cells, Fludarabine and Cyclophosphamide in people with Acute Lymphocytic Leukemia, run by Chinese PLA General Hospital at 2 sites in China.
Trial summary
In this single-center, single-arm, prospective, Phase 1/2 study, the safety and efficacy of autologous BCOR and ZC3H12 genes knock-out CD19-targeting chimeric antigen receptor (CAR) T-cell therapy will be evaluated in patients with refractory/relapsed (r/r) B-cell acute lymphoblastic leukaemia (B-ALL). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Acute Lymphocytic Leukemia
- What is being tested?
- CAR19TIF cells, Fludarabine and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesChina
- Study dates
- 20 Jun 2025to 31 May 2027
- 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-70 (inclusive),gender unrestricted.
- Patient with r/r CD19+ B-ALL, as per guidelines (NCCN, 2019)
- morphologically confirmed with ≥ 5% leukaemic blasts in the bonemarrow;
- or presenting a quantifiable MRD load of 1x10^-3 , assessed by multiparameter flow cytometry and/or quantitative polymerase chain reaction, at the end of the last induction treatment.
- who has exhausted alternative treatment options.
- Relapsed disease is defined as:
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- second or subsequent bone marrow relapse or,
- any bone marrow relapse after allogenic hematopoiesis stem cell transplant (allo-HSCT).
- Refractory disease is defined by not achieving an initial complete response (CR) after 2 cycles of a standard chemotherapy regimen (primary refractory). Subjects who were refractory to subsequent chemotherapy regimens after an initial remission were considered chemorefractory.
- Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for hematological toxicities and clinically non-significant toxicities such as alopecia).
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
- Adequate renal, hepatic, pulmonary and cardiac function defined as:
- Serum creatinine≤1.5 upper limit of normal (ULN) or creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min.
- Serum alanine aminotransferase / aspartate aminotransferase (ALT/AST) ≤ 3×ULN; Total bilirubin ≤ 1.5×ULN.
- Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings.
- Coagulation Function: International Normalized Ratio (INR) ≤ 1.5 ×ULN, and Activated Partial Thromboplastin Time (APTT) ≤ 1.5×ULN .• Baseline oxygen saturation >91% on room air.
- Subjects of both genders who are willing to practice birth control from the time of consent through 6 months after the completion of conditioning chemotherapy. Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential).
- Voluntarily participate in this clinical trial and sign an informed consent form.
Who cannot join
- Expected survival time < 3 months per Principal Investigator's opinion.
- Previous or concurrent cancer within 3 years prior to treatment start EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)].
- Prior CD19 targeted therapy
- Prior CAR-T therapy or other genetically modified T cell therapy.
- Active central nervous system (CNS) leukaemia (CNS-3).
- B-ALL with clinically suspected extra-medullary involvement.
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- Burkitt cell (L3 ALL) or mixed lineage acute leukaemia.
- Clinically active significant CNS dysfunction
- History or presence of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
- Known history of irreversible severe neurological toxicity related to previous antileukaemic treatment leading to organic central nervous system lesions.
- Radioimmunotherapy, radiotherapy, within 8 weeks (except prophylaxis of CNS involvement) before Inclusion.
- Use of previous anti-leukemic therapy within 5 half-lives prior to CAR19TIF cells administration; participation in non-interventional registries or epidemiological studies is allowed.
- History of severe, immediate hypersensitivity reaction attributed to lymphodepletion drugs or any component of CAR19TIF cells.
- Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management.
- Uncontrolled or active infectious diseases, such as human immunodeficiency virus (HIV) infection, acute or chronic active hepatitis B or C, epstein-barr virus (EBV), and cytomegalovirus (CMV) infection.
- Subjects with cardiac atrial or cardiac ventricular lymphoma involvement.
- History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment.
- Expected or possible requirement for urgent therapy within 6 weeks due to ongoing or impending oncologic emergency (eg, tumor mass effect, tumor lysis syndrome).
- Primary immunodeficiency.
- History of autoimmune disease (e.g. Crohn's, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years.
- History of symptomatic deep vein thrombosis or pulmonary embolism requiring systemic anticoagulation within 6 months of enrollment.
- Any medical condition likely to interfere with assessment of safety or efficacy of study treatment.
- Vaccine ≤ 6 weeks prior to planned start of conditioning regimen.
- In the investigator's judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites, 2 recruiting
- Recruiting
China
Beijing, Biotherapeutic Department of Chinese PLA General Hospital
Weidong Han, Ph.D, 010-66937463, hanwdrsw69@yahoo.com
Yang Liu, M.D, 010-66939460, liuyang301blood@163.com
- Not yet recruiting
China
Beijing, Biotherapeutic Department of Chinsese PLA Gereral Hospital
Weidong Han, Ph.D, 010-66937231, hanwdrsw@sina.com
Yang Liu, M.D, 010-66939460, liuyang301blood@163.com
About this study
Official title: A Phase I/II Single-center Study Evaluating the Safety and Efficacy of BCOR and ZC3H12 Genes Knock-out CD19-targeting CAR-T Cell Therapy in Adults With Refractory/Relapsed B-cell Acute Lymphoblastic Leukaemia
In this single-center, single-arm, prospective, Phase 1/2 study, the safety and efficacy of autologous BCOR and ZC3H12 genes knock-out CD19-targeting chimeric antigen receptor (CAR) T-cell therapy will be evaluated in patients with refractory/relapsed (r/r) B-cell acute lymphoblastic leukaemia (B-ALL).
In phase 1, 3 eligible patients will be enrolled and receive BCOR and ZC3H12 genes knock-out CD19 CAR T cell therapy at a initial dose of 5×10^5 cells/kg. Based on the results, . Subsequently an additional 3-15 patients will be enrolled in a "3+3" dose-escalation/decline design to adjust the dose of BCOR and ZC3H12 genes knock-out CD19 CAR T cells to achieve optimal safety and efficacy. The recommended Phase 2 dose (RP2D) will then be established. 10 to 12 subjects will be enrolled and receive BCOR and ZC3H12 genes knock-out CD19 CAR T cell infusion at dose of RP2D.
Read the detailed description
CAR T-cell therapy targeting CD19 has transformed the management of r/r B-ALL, complete remission (CR) or complete response with incomplete count recovery (CRi) has been achieved as many as 70-90% in r/r B-ALL cases. Unfortunately, 40-60% of patients responding to this therapy relapse within 1 year due to challenges such as limited CAR T cell persistence,T cell exhaustion,etc. These limitations highlighted the need for further optimization of the CAR T cell design to improve the efficiency of CD19-targeted CAR T cell therapy in r/r B-ALL.
The investigators have developed that the suppression of two genes, Zc3h12a and Bcor, induced CD19 CAR T cells capable of expansion, persistence, and inducing long-term B cell depletion in immunocompetent mice models,even without any conditioning and in low dose infusion. From this, the investigators present a single-center, single-arm, prospective, phase 1/2 study to evaluate the safety and efficacy of BCOR and ZC3H12 genes knock-out CD19 CAR T cells in adult patients with r/r B-ALL. For simplicity, the investigators have termed these CD19 CAR T cells lacking ZC3H12A and BCOR as immortal-like and functional CD19 CAR T (CAR19TIF) cells, reflecting their immortal-like and functional characteristics.
Phase 1 (dose escalation/decline)
In phase 1, 6-18 subjects will be enrolled. Referring to the starting dose of most CAR T cell therapies, and to avoid exposing patients to the risk of "ineffective expansion dose", 3 patients will receive CAR19TIF cells therapy at a starting dose of 5×10^5 cells/kg.According to the copy number of CAR T cells were assessed by number in peripheral blood and clinical efficacy data, additional 3-15 patients will be enrolled in a "3+3" dose-escalation/decline design to adjust the dose of CAR19TIF cells to achieve optimal safety and efficacy :
After obtaining effective expansion data and clinical efficacy data, a descending dose escalation model will be adopted: such as 1×10^5 cells/kg, 5×10^4 cells/kg. If the 5×10^5 cells/kg dose group does not achieve efficient expansion and clinical benefit, an ascending dose escalation model will be adopted, such as 2×10^6 cells/kg, 6×10^6 cells/kg.
3 subjects are enrolled in a cohort corresponding to a dose level. If 1 subject in a cohort of 3 subjects experiences a DLT, 3 additional subjects will be enrolled at the current dose level.
For safety purposes, the administration of CAR19TIF cells will be staggered by 28 days between the first two subjects in each cohort. And for each of the remaining cohorts, the administration of CAR19TIF cells will be staggered by 28 day.
Phase 2 (expansion cohort) In phase 2, 10 to 12 subjects will be enrolled and receive cell infusion at dose of RP2D, which will be determined based on the maximum tolerated dose (MTD), occurrence of DLT, the obtained efficacy results, pharmacokinetics/pharmacodynamics and other data according to the phase 1.
Objectives The primary objectives of the phase 1 were to evaluate the tolerability and safety of CAR19TIF cells in patients with r/r B-ALL, and determine RP2D. The primary purpose of the phase 2 study was to evaluate the efficacy of CAR19TIF cells n the above population.
- Conditions
- Acute Lymphocytic Leukemia
- Being tested
- CAR19TIF cells, Fludarabine, Cyclophosphamide
- Keywords
- CAR-T cells, ALL, CD19
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAR19TIF cellsBiological
Also called BCOR and ZC3H12 genes knock-out CD19 CAR T cells
Phase 1 dose escalation/decline (3+3) :
starting dose: 5×10^5 cells/kg, According to effective expansion and clinical efficacy data, a descending dose escalation model will be adopted: such as 1×10^5 cells/kg, 5×10^4 cells/kg.
If the 5×10^5 cells/kg dose group does not achieve efficient expansion and clinical benefit, an ascending dose escalation model will be adopted, such as 2×10^6 cells/kg, 6×10^6 cells/kg.
Phase 2 : dose of RP2D.
FludarabineDrug
Also called Fludarabine Phosphate for Injection
Intravenous fludarabine 25~30 mg/m^2/day on days
-5, -4, and -3.
CyclophosphamideDrug
Also called Cyclophosphamide for Injection
Intravenous cyclophosphamide 250~500 mg/m^2/day on days -5, -4, and -3.
| Study group | Role | What they receive |
|---|---|---|
| CAR19TIF cells | Experimental | Patients with r/r B-ALL A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, CAR19TIF cells. Receives: Biological: CAR19TIF cells; Drug: Fludarabine; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Incidence of Adverse Events (AEs)
AE is defined as any adverse medical event from the date of randomization to 12 months after CAR T cells infusion. Among them, cytokine release syndrome(CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria. Other AEs were graded according to common terminology criteria for adverse events (CTCAE) v5.0.
Measured: Up to 12 months since the initiation of CAR-T cell therapy.
Phase 1:Incidence of Incidence of Dose-Limiting Toxicities (DLTs)
DLT is defined as any AE related to the investigational drug that occurs within 28 days after administration of the CAR19TIF cells and meets any one of the criteria listed in the DLT criteria:
- Grade 3 CRS that does not resolve to grade 2 or lower within 2 weeks;
- Grade 3 ICANS lasting for ≥ 7 days;
- Any Grade ≥ 4 CRS or ICANS;
- Any other Grade ≥ 4 and Grade 3 AEs related to the CAR19TIF cells that lasts for ≥ 14 days, except hematology toxicity.
Measured: [Time Frame: Up to 28 days since the initiation of CAR-T cell therapy]
Phase 1:RP2D
The recommended dose for phase 2 was determined through phase 1 study.
Measured: 12 months
Phase 2:Objective response rate (ORR)
Objective response definition: a molecular response (MRD < 10^-4 post treatment) assessed by multiparameter flow cytometry and/or qPCR, or a morphologic complete response (CR), or a CR with incomplete blood count recovery (CRi). ORR is defined as the proportion of patients who have achieved objective response assessed by investigators.
Measured: 24 months
Phase 2:Overall Survival (OS)
OS is defined as the time from CAR-T cells infusion to the date of death. Subjects who have not died by the analysis data cutoff date will be censored at the last contact date.
Measured: 24 months
Phase 2: Progression Free Survival (PFS)
PFS is defined as the time from the CAR-T cells infusion date to the date of disease progression assessed by investigators, or death any cause. Participants not meeting the criteria for progression by the analysis data cutoff date were censored at the last evaluable disease assessment date.
Measured: 24 months
Secondary outcomes (2)
Phase 1 and phase 2: Level of CAR-positive T cells circulating in blood over time
Number and copy number of CAR-T cells were assessed by number in peripheral blood. Blood samples were collected before and one year after cell infusion (until CAR-T cells were not detected for two consecutive times) to detect the number and copy number of CAR-T cells, and to evaluate the pharmacokinetics of CAR-T.
Measured: 12 months
Phase 1 and phase 2: Level of CD19+ cells in peripheral blood
The level of CD19+ cells in peripheral blood will be detected by flow cytometry.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2025
- Study start20 Jun 2025
- Primary completion31 May 2026 (estimated)
- Study completion31 May 2027 (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.
- More trials run by Chinese PLA General HospitalThe sponsor's other registered studies.
- 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
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese PLA General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Han weidong, Chinese PLA General Hospital
- Investigators
- Weidong Han, Ph.D, Principal investigator, Biotherapeutic Department, Chinese PLA General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07008885
- Sponsor's protocol ID
- CHN-PLAGH-BT-090
- Status last verified
- Jun 2025
- First submitted
- 21 May 2025
- Last updated
- 25 Jun 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Single-center Study Evaluating the Safety and Efficacy of BCOR and ZC3H12 Genes Knock-out CD19-targeting CAR-T Cell Therapy in Adults With Refractory/Relapsed B-cell Acute Lymphoblastic Leukaemia
- ClinicalTrials.gov ID
- NCT07008885
- Acronym / sponsor ID
- CHN-PLAGH-BT-090
- Conditions
- Acute Lymphocytic Leukemia
- Keywords
- CAR-T cells, ALL, CD19
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Chinese PLA General HospitalUniversity, hospital or other
- Study start
- 20 Jun 2025 (actual)
- Primary completion
- 31 May 2026 (estimated)
- Study completion
- 31 May 2027 (estimated)
- First posted
- 6 Jun 2025 (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.
In this single-center, single-arm, prospective, Phase 1/2 study, the safety and efficacy of autologous BCOR and ZC3H12 genes knock-out CD19-targeting chimeric antigen receptor (CAR) T-cell therapy will be evaluated in patients with refractory/relapsed (r/r) B-cell acute lymphoblastic leukaemia (B-ALL).
In phase 1, 3 eligible patients will be enrolled and receive BCOR and ZC3H12 genes knock-out CD19 CAR T cell therapy at a initial dose of 5×10^5 cells/kg. Based on the results, . Subsequently an additional 3-15 patients will be enrolled in a "3+3" dose-escalation/decline design to adjust the dose of BCOR and ZC3H12 genes knock-out CD19 CAR T cells to achieve optimal safety and efficacy. The recommended Phase 2 dose (RP2D) will then be established. 10 to 12 subjects will be enrolled and receive BCOR and ZC3H12 genes knock-out CD19 CAR T cell infusion at dose of RP2D.
Detailed description
CAR T-cell therapy targeting CD19 has transformed the management of r/r B-ALL, complete remission (CR) or complete response with incomplete count recovery (CRi) has been achieved as many as 70-90% in r/r B-ALL cases. Unfortunately, 40-60% of patients responding to this therapy relapse within 1 year due to challenges such as limited CAR T cell persistence,T cell exhaustion,etc. These limitations highlighted the need for further optimization of the CAR T cell design to improve the efficiency of CD19-targeted CAR T cell therapy in r/r B-ALL.
The investigators have developed that the suppression of two genes, Zc3h12a and Bcor, induced CD19 CAR T cells capable of expansion, persistence, and inducing long-term B cell depletion in immunocompetent mice models,even without any conditioning and in low dose infusion. From this, the investigators present a single-center, single-arm, prospective, phase 1/2 study to evaluate the safety and efficacy of BCOR and ZC3H12 genes knock-out CD19 CAR T cells in adult patients with r/r B-ALL. For simplicity, the investigators have termed these CD19 CAR T cells lacking ZC3H12A and BCOR as immortal-like and functional CD19 CAR T (CAR19TIF) cells, reflecting their immortal-like and functional characteristics.
Phase 1 (dose escalation/decline)
In phase 1, 6-18 subjects will be enrolled. Referring to the starting dose of most CAR T cell therapies, and to avoid exposing patients to the risk of "ineffective expansion dose", 3 patients will receive CAR19TIF cells therapy at a starting dose of 5×10^5 cells/kg.According to the copy number of CAR T cells were assessed by number in peripheral blood and clinical efficacy data, additional 3-15 patients will be enrolled in a "3+3" dose-escalation/decline design to adjust the dose of CAR19TIF cells to achieve optimal safety and efficacy :
After obtaining effective expansion data and clinical efficacy data, a descending dose escalation model will be adopted: such as 1×10^5 cells/kg, 5×10^4 cells/kg. If the 5×10^5 cells/kg dose group does not achieve efficient expansion and clinical benefit, an ascending dose escalation model will be adopted, such as 2×10^6 cells/kg, 6×10^6 cells/kg.
3 subjects are enrolled in a cohort corresponding to a dose level. If 1 subject in a cohort of 3 subjects experiences a DLT, 3 additional subjects will be enrolled at the current dose level.
For safety purposes, the administration of CAR19TIF cells will be staggered by 28 days between the first two subjects in each cohort. And for each of the remaining cohorts, the administration of CAR19TIF cells will be staggered by 28 day.
Phase 2 (expansion cohort) In phase 2, 10 to 12 subjects will be enrolled and receive cell infusion at dose of RP2D, which will be determined based on the maximum tolerated dose (MTD), occurrence of DLT, the obtained efficacy results, pharmacokinetics/pharmacodynamics and other data according to the phase 1.
Objectives The primary objectives of the phase 1 were to evaluate the tolerability and safety of CAR19TIF cells in patients with r/r B-ALL, and determine RP2D. The primary purpose of the phase 2 study was to evaluate the efficacy of CAR19TIF cells n the above population.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CAR19TIF cells | Experimental | Biological: CAR19TIF cells, Drug: Fludarabine, Drug: CyclophosphamidePatients with r/r B-ALL A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, CAR19TIF cells. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Age 18-70 (inclusive),gender unrestricted.
- Patient with r/r CD19+ B-ALL, as per guidelines (NCCN, 2019)
- Refractory disease is defined by not achieving an initial complete response (CR) after 2 cycles of a standard chemotherapy regimen (primary refractory). Subjects who were refractory to subsequent chemotherapy regimens after an initial remission were considered chemorefractory.
- Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for hematological toxicities and clinically non-significant toxicities such as alopecia).
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
Key exclusion criteria (24 listed)
- Expected survival time < 3 months per Principal Investigator's opinion.
- Previous or concurrent cancer within 3 years prior to treatment start EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)].
- Prior CD19 targeted therapy
- Prior CAR-T therapy or other genetically modified T cell therapy.
- Active central nervous system (CNS) leukaemia (CNS-3).
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 |
|---|---|---|
| CAR19TIF cellsAlso: BCOR and ZC3H12 genes knock-out CD19 CAR T cellsPhase 1 dose escalation/decline (3+3) : starting dose: 5×10^5 cells/kg, According to effective expansion and clinical efficacy data, a descending dose escalation model will be adopted: such as 1×10^5 cells/kg, 5×10^4 cells/kg. If the 5×10^5 cells/kg dose group does not achieve efficient expansion and clinical benefit, an ascending dose escalation model will be adopted, such as 2×10^6 cells/kg, 6×10^6 cells/kg. Phase 2 : dose of RP2D. | Biological | CAR19TIF cells |
| FludarabineAlso: Fludarabine Phosphate for InjectionIntravenous fludarabine 25~30 mg/m^2/day on days -5, -4, and -3. | Drug | CAR19TIF cells |
| CyclophosphamideAlso: Cyclophosphamide for InjectionIntravenous cyclophosphamide 250~500 mg/m^2/day on days -5, -4, and -3. | Drug | CAR19TIF cells |
Primary outcome
Phase 1: Incidence of Adverse Events (AEs)
Time frame: Up to 12 months since the initiation of CAR-T cell therapy.
AE is defined as any adverse medical event from the date of randomization to 12 months after CAR T cells infusion. Among them, cytokine release syndrome(CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria. Other AEs were graded according to common terminology criteria for adverse events (CTCAE) v5.0.
Phase 1:Incidence of Incidence of Dose-Limiting Toxicities (DLTs)
Time frame: [Time Frame: Up to 28 days since the initiation of CAR-T cell therapy]
DLT is defined as any AE related to the investigational drug that occurs within 28 days after administration of the CAR19TIF cells and meets any one of the criteria listed in the DLT criteria: * Grade 3 CRS that does not resolve to grade 2 or lower within 2 weeks; * Grade 3 ICANS lasting for ≥ 7 days; * Any Grade ≥ 4 CRS or ICANS; * Any other Grade ≥ 4 and Grade 3 AEs related to the CAR19TIF cells that lasts for ≥ 14 days, except hematology toxicity.
Phase 1:RP2D
Time frame: 12 months
The recommended dose for phase 2 was determined through phase 1 study.
Phase 2:Objective response rate (ORR)
Time frame: 24 months
Objective response definition: a molecular response (MRD < 10^-4 post treatment) assessed by multiparameter flow cytometry and/or qPCR, or a morphologic complete response (CR), or a CR with incomplete blood count recovery (CRi). ORR is defined as the proportion of patients who have achieved objective response assessed by investigators.
Phase 2:Overall Survival (OS)
Time frame: 24 months
OS is defined as the time from CAR-T cells infusion to the date of death. Subjects who have not died by the analysis data cutoff date will be censored at the last contact date.
Phase 2: Progression Free Survival (PFS)
Time frame: 24 months
PFS is defined as the time from the CAR-T cells infusion date to the date of disease progression assessed by investigators, or death any cause. Participants not meeting the criteria for progression by the analysis data cutoff date were censored at the last evaluable disease assessment date.
2 secondary outcomes
Phase 1 and phase 2: Level of CAR-positive T cells circulating in blood over time
Time frame: 12 months
Phase 1 and phase 2: Level of CD19+ cells in peripheral blood
Time frame: 12 months
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 25 Jun 2025.
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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.
Weidong Han, Ph.D principal investigator
Biotherapeutic Department, Chinese PLA General Hospital
2 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 CAR19TIF cells, Fludarabine and Cyclophosphamide in people with Acute Lymphocytic Leukemia, run by Chinese PLA General Hospital at 2 sites 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 18 inclusion and 24 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: looking for participants now, as of the sponsor's last update on 25 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 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?
Contact Weidong Han, Ph.D (010-66937231 ext. +86, hanwdrsw@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: Incidence of Adverse Events (AEs) (time frame: Up to 12 months since the initiation of CAR-T cell therapy.). The study lists 6 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 25 Jun 2025.