- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT07696481
Clinical Study on the Safety and Efficacy of PID23 Injection in Patients With Relapsed/Refractory Acute Leukemia (R/R AL)
A Single-center, Single-arm, Open-label Clinical Study on the Safety and Efficacy of PID23 Injection in Treating Patients With Relapsed/Refractory Acute Leukemia
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Type d'étude
Inscription (Estimé)
Phase
- Première phase 1
Contacts et emplacements
Coordonnées de l'étude
- Nom: Yuhua Li, PhD
- Numéro de téléphone: +86-020-61643188
- E-mail: liyuhua2011gz@163.com
Lieux d'étude
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Guangdong
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Guangzhou, Guangdong, Chine, 510282
- Department of Hematology, Zhujiang Hospital, Southern Medical University
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Contact:
- Yuhua Li, PhD
- Numéro de téléphone: +86-020-62782316
- E-mail: liyuhua2011gz@163.com
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Contact:
- E-mail: zhoulijanice@foxmail.com
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
- Enfant
- Adulte
- Adulte plus âgé
Accepte les volontaires sains
La description
Inclusion Criteria:
- Patient or legal guardian voluntarily signs the informed consent form (ICF), demonstrating understanding of the study purpose and procedures, and willingness to participate.
- Age 3 to 75 years, inclusive, male or female.
- 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:
- Cardiac: left ventricular ejection fraction (LVEF) ≥40% by echocardiogram;
- Renal: serum creatinine ≤2.0× upper limit of normal (ULN), or creatinine clearance ≥50 mL/min (Cockcroft-Gault formula);
- 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);
- Pulmonary: oxygen saturation ≥92% on room air;
- 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:
- Prior treatment with CAR-T or other genetically modified cell therapies, unless the investigator determines that safety risks have been adequately excluded.
- 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.
- 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.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Expérimental: PID23 Injection (Dose Escalation)
Participants receive a single intravenous infusion of PID23 Injection at one of three dose levels (0.8×10⁹, 2×10⁹, or 4×10⁹ TU) according to a rapid titration + standard 3+3 dose-escalation design.
The starting dose is 0.8×10⁹ TU, with escalation to higher dose levels guided by safety and pharmacokinetic assessments.
All subjects are hospitalized for observation for at least 3 weeks post-infusion and followed for up to 2 years.
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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
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Incidence of Dose-Limiting Toxicities (DLTs)
Délai: Up to 21 days post-PID23 infusion
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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.
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Up to 21 days post-PID23 infusion
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Incidence and Severity of Treatment-Emergent Adverse Events
Délai: Up to 2 years post-PID23 infusion
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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.
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Up to 2 years post-PID23 infusion
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Objective Response Rate at 3 Months
Délai: At 3 months post-infusion
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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.
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At 3 months post-infusion
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Duration of Remission (DOR)
Délai: Up to 2 years post-infusion
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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.
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Up to 2 years post-infusion
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Progression-Free Survival (PFS)
Délai: Up to 2 years post-infusion
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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.
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Up to 2 years post-infusion
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Overall Survival (OS)
Délai: Up to 2 years post-infusion
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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.
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Up to 2 years post-infusion
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Change from Baseline in Bone Marrow Blast Percentage
Délai: Baseline through 2 years post-infusion
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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.
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Baseline through 2 years post-infusion
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Maximum Concentration (Cmax) of CAR-T Cells in Peripheral Blood
Délai: Day 0 through 2 years post-infusion
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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.
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Day 0 through 2 years post-infusion
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Time to Maximum Concentration (Tmax) of CAR-T Cells
Délai: Day 0 through 2 years post-infusion
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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.
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Day 0 through 2 years post-infusion
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Area Under the Curve (AUC0-28d) of CAR-T Cells
Délai: Day 0 through Day 28
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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.
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Day 0 through Day 28
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Change from Baseline in Serum Cytokine Levels
Délai: Baseline through Month 1
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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.
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Baseline through Month 1
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Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Viral Clearance from Body Fluids
Délai: Day 0 through Month 1 or until two consecutive negatives, whichever came first
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Detection of viral vector sequences in body fluid samples including blood, saliva, urine, and stool.
Viral clearance is defined as two consecutive negative results.
Samples collected at protocol-specified time points: 0h, 30min, 2h, 6h, 12h, D2, D4, D7, D10, D14, D21, and M1.
Samples may be stored at -80°C and shipped in batches to the technology partner for analysis.
Viral clearance assessed until two consecutive negative results are obtained.
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Day 0 through Month 1 or until two consecutive negatives, whichever came first
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Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Estimé)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Processus pathologiques
- Tumeurs
- Attributs de la maladie
- Maladies du système immunitaire
- Tumeurs par type histologique
- Maladies hématologiques
- Maladies lymphatiques
- Troubles lymphoprolifératifs
- Troubles immunoprolifératifs
- Leucémie myéloïde
- Leucémie, Lymphoïde
- Leucémie
- Conditions pathologiques, signes et symptômes
- Maladies hémiques et lymphatiques
- Récurrence
- Leucémie, myéloïde, aiguë
- Leucémie-lymphome lymphoblastique à cellules précurseurs
Autres numéros d'identification d'étude
- 2026-KY-163-01
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Description du régime IPD
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Étudie un produit d'appareil réglementé par la FDA américaine
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