Relapsed or Refractory Acute Leukemia, Relapsed or Refractory Acute Lymphoblastic Leukemia, Relapsed or Refractory Acute Myeloid Leukemia (AML)
Conditions
Keywords
PID23, In vivo CAR-T, Acute Leukemia, Relapsed, Refractory, AML, B-ALL, Acute Myeloid Leukemia, Acute lymphoblastic leukemia
Brief summary
Relapsed or refractory acute leukemia (R/R AL) is a life-threatening blood cancer with poor outcomes and limited treatment options. PID23 Injection is an innovative in vivo CAR-T therapy that delivers a viral vector encoding three targets (CD19, BCMA, and CD70) directly into patients, enabling their own T cells to generate functional CAR-T cells against leukemia cells. This single-center, single-arm, open-label, dose-escalation study (3 dose levels: 0.8×10⁹, 2×10⁹, and 4×10⁹ TU) plans to enroll 3-18 patients with R/R AL aged 3-75 years, ECOG 0-2, and positive for at least one target. The primary objective is to evaluate safety, tolerability, and determine the recommended dose. Secondary objectives include preliminary efficacy (remission, survival), pharmacokinetics (CAR-T expansion), pharmacodynamics (cytokine changes), and exploratory viral clearance. After a single intravenous infusion, patients are hospitalized for ≥3 weeks, followed by monthly visits for 3 months, then every 3 months for up to 2 years. Enrollment is from May 2026 to May 2027, with follow-up through May 2029. The study is conducted at Zhujiang Hospital of Southern Medical University (PI: Prof. Li Yuhua).
Interventions
BIOLOGICALPID23 Injection
PID23 is an in vivo CAR-T product, a lentiviral vector encoding CD19, BCMA, and CD70 chimeric antigen receptors, administered as a single intravenous infusion
Sponsors
Zhujiang Hospital
Chongqing Precision Biotech Co., Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single-arm, open-label, dose-escalation study using rapid titration + standard 3+3 design at 3 dose levels (0.8, 2, 4 ×10⁹ TU). Each level enrolls 1 sentinel subject; after 21 days (DL1) or 14 days (DL2/3) observation, PK and safety data guide decision: escalate to next dose if no DLT, or switch to 3+3 if DLT observed. Under 3+3: 0/3 DLT → escalate; 1/3 → expand to 6; ≥2/3 or ≥2/6 → stop escalation. MTD defined as highest dose with ≤1/6 DLT, but optimal dose determined by integrating safety, efficacy, and PK/PD, not solely MTD. If CAR-T expansion is suboptimal (Cmax \<1/10 of prior mean \ 10,000 copies/μg) at day 21 with no DLT and no blast reduction, a second identical dose may be considered after investigator evaluation.
Eligibility
Sex/Gender
ALL
Age
3 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Patient or legal guardian voluntarily signs the informed consent form (ICF), demonstrating understanding of the study purpose and procedures, and willingness to participate. 2. Age 3 to 75 years, inclusive, male or female. 3. Diagnosis of relapsed or refractory acute leukemia per guideline criteria: Relapsed: reappearance of leukemic cells in peripheral blood or bone marrow blasts ≥5% after achieving complete remission (CR); Refractory: failure to achieve CR after 2 courses of standard induction chemotherapy; relapse within 12 months after consolidation/intensification therapy; relapse after 12 months with no response to conventional chemotherapy; 2 or more relapses; extramedullary leukemia relapse or persistence; relapse after allogeneic hematopoietic stem cell transplantation. 4.Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. 5.Life expectancy ≥12 weeks. 6.Bone marrow morphology showing ≥5% primitive/immature lymphocytes (blasts). 7.Tumor cells positive for CD19, BCMA, or CD70 expression by flow cytometry. 8.Adequate major organ function, defined as: 1. Cardiac: left ventricular ejection fraction (LVEF) ≥40% by echocardiogram; 2. Renal: serum creatinine ≤2.0× upper limit of normal (ULN), or creatinine clearance ≥50 mL/min (Cockcroft-Gault formula); 3. Hepatic: ALT and AST ≤3.0×ULN (≤5.0×ULN if with liver involvement); total bilirubin ≤2.0×ULN (≤3.0×ULN for Gilbert's syndrome); 4. Pulmonary: oxygen saturation ≥92% on room air; 5. Hematologic: absolute neutrophil count (ANC) ≥1.0×10⁹/L, platelets ≥50×10⁹/L, hemoglobin ≥80 g/L (with bone marrow involvement, ANC ≥0.5×10⁹/L, platelets ≥20×10⁹/L permitted) - assessments allowed after transfusion or hematopoietic growth factor support. 9\. For women of childbearing potential, negative serum pregnancy test; all participants agree to use reliable (non-rhythm) contraceptive methods from ICF signing through 1 year post-PID23 infusion.
Exclusion criteria
1. Prior treatment with CAR-T or other genetically modified cell therapies, unless the investigator determines that safety risks have been adequately excluded. 2. Received the following anti-tumor therapies prior to PID23 infusion: Chemotherapy or molecular targeted therapy within 14 days or 5 half-lives (whichever is longer) (excluding conditioning chemotherapy and intrathecal chemotherapy; intrathecal therapy must be stopped ≥1 week prior to PID23 infusion); Radiotherapy to non-hematopoietic sites within 7 days; Radiotherapy to hematopoietic sites within 14 days. 3. Any of the following cardiac conditions: (1) New York Heart Association (NYHA) Class III or IV congestive heart failure; (2) Myocardial infarction or coronary artery bypass grafting (CABG) within 6 months prior to enrollment; (3) Clinically significant ventricular arrhythmia, or unexplained syncope (excluding vasovagal or dehydration-related); (3) History of severe non-ischemic cardiomyopathy. 4.Active or uncontrolled infection requiring systemic therapy within 1 week prior to screening. 5.Grade 2-4 acute graft-versus-host disease (GVHD) or moderate-to-severe chronic GVHD within 4 weeks prior to screening. 6.Cerebrovascular accident or seizure within 6 months prior to screening. 7.Deep vein or arterial thrombosis event within 6 months prior to screening. 8.Active malignancy other than acute leukemia (excluding: inactive disease with treatment completed \>2 years; adequately treated cervical carcinoma in situ, basal/squamous cell skin carcinoma, localized prostate cancer post-curative surgery, ductal carcinoma in situ post-curative surgery). 9.Received (attenuated) live vaccine within 4 weeks prior to screening. 10.Any other condition that, in the investigator's judgment, makes the patient unsuitable for participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose-Limiting Toxicities (DLTs) | Up to 21 days post-PID23 infusion | Number of participants experiencing DLTs during the DLT observation period. DLT is defined as any treatment-emergent adverse event meeting protocol-specified severity criteria assessed per CTCAE v6.0 and ASTCT criteria for CRS/ICANS. |
| Incidence and Severity of Treatment-Emergent Adverse Events | Up to 2 years post-PID23 infusion | Number and percentage of participants experiencing adverse events (AEs), graded per CTCAE v6.0. Includes all AEs, serious AEs (SAEs), and AEs of special interest (CRS, ICANS, HLH/MAS). Causality assessment performed by the investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate at 3 Months | At 3 months post-infusion | Proportion of participants achieving complete remission (CR) or CR with incomplete blood count recovery (CRi) at 3 months post-infusion. CR defined as bone marrow blasts \<5%, no peripheral blasts, ANC ≥1.0×10⁹/L, platelets ≥100×10⁹/L, no extramedullary disease. CRi defined as meeting all CR criteria except platelet \<100×10⁹/L and/or ANC \<1.0×10⁹/L. |
| Duration of Remission (DOR) | Up to 2 years post-infusion | Time from first documented CR or CRi to first documented disease progression (PD) or death from any cause, whichever occurs first. Participants who do not achieve CR/CRi are not applicable for this analysis. Assessed per protocol until 2 years post-infusion. |
| Progression-Free Survival (PFS) | Up to 2 years post-infusion | Time from PID23 infusion to first documented disease progression (PD) or death from any cause, whichever occurs first. Participants alive without progression are censored at the date of last disease assessment. Assessed per protocol through 2 years post-infusion or until event. |
| Overall Survival (OS) | Up to 2 years post-infusion | Time from PID23 infusion to death from any cause. Participants alive at the end of follow-up are censored at the date of last known survival status. Assessed through 2 years post-infusion or until death, whichever occurs first. |
| Change from Baseline in Bone Marrow Blast Percentage | Baseline through 2 years post-infusion | Change from baseline in percentage of bone marrow blasts assessed by bone marrow morphology. Measured at screening and at protocol-specified follow-up time points (M1, M2, M3, and every 3 months thereafter). Assessed per protocol schedule. |
| Maximum Concentration (Cmax) of CAR-T Cells in Peripheral Blood | Day 0 through 2 years post-infusion | Maximum concentration (Cmax) of CAR-T cells in peripheral blood, measured as CAR DNA copy number by quantitative PCR (copies/μg DNA) and/or percentage of CAR+ cells by flow cytometry. Blood samples collected at protocol-specified time points: 0h, 30min, 2h, 6h, 12h, D2, D4, D7, D10, D14, D21, M1, M2, M3, and long-term follow-up. Samples analyzed by the technology partner. |
| Time to Maximum Concentration (Tmax) of CAR-T Cells | Day 0 through 2 years post-infusion | Time to reach maximum concentration (Tmax) of CAR-T cells in peripheral blood, measured as CAR DNA copy number by quantitative PCR. Blood samples collected at protocol-specified time points from immediately post-infusion through long-term follow-up. Tmax determined from the concentration-time profile. |
| Area Under the Curve (AUC0-28d) of CAR-T Cells | Day 0 through Day 28 | Area under the concentration-time curve from Day 0 to Day 28 (AUC0-28d) of CAR-T cells in peripheral blood, measured as CAR DNA copy number by quantitative PCR. Calculated using the linear trapezoidal rule. Blood samples collected at protocol-specified time points through Day 28. |
| Change from Baseline in Serum Cytokine Levels | Baseline through Month 1 | Change from baseline in serum cytokine concentrations, including but not limited to IL-6, IL-1β, IL-2/IL-2R, IL-8, IL-10, TNF-α, IFN-γ, CRP, and ferritin. Blood samples collected at protocol-specified time points: screening, D0 (pre-infusion), D2, D4, D7, D10, D14, and M1. |
Countries
China
Contacts
CONTACTYuhua Li, PhD
Outcome results
None listed