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Dual-Targeted Umbilical Cord Blood CAR-T Cells Against CD19 and CD22 for the Treatment of Relapsed or Refractory Acute B-Cell Lymphoblastic Leukemia

24 septembre 2026 mis à jour par: Jin Wang, Ruijin Hospital

A Single-Center Phase I Clinical Trial of Dual-Targeted Umbilical Cord Blood CAR-T Cells Against CD19 and CD22 for the Treatment of Relapsed or Refractory Acute B-Cell Lymphoblastic Leukemia

This investigator-initiated, prospective, single-arm, phase I dose-escalation trial aims to evaluate the safety and tolerability of anti-CD19/CD22 dual-target cord blood-derived CAR-T cells in adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia who have failed prior therapies, with the goal of reducing antigen-escape relapse and overcoming poor autologous T-cell fitness through the use of universally available umbilical cord blood T cells.

Aperçu de l'étude

Statut

Recrutement

Les conditions

Intervention / Traitement

Description détaillée

Patients with relapsed/refractory B-cell acute lymphoblastic leukemia who meet eligibility criteria will receive fludarabine (30 mg/m²/d) and cyclophosphamide (300 mg/m²/d) for three consecutive days as lymphodepleting conditioning, followed by a single intravenous infusion of anti-CD19/CD22 dual-target cord blood-derived CAR-T cells. Dose assignment follows a "3+3" escalation design across three dose levels (4×10⁶, 8×10⁶, and 12×10⁶ CAR-T/kg, ±20%). Dose-limiting toxicity will be assessed during the first 14 days post-infusion to determine the maximum tolerated dose. After CAR-T infusion, patients will be monitored for safety and efficacy at protocol-specified time points through 3 months, with long-term follow-up continuing up to 15 years post-infusion. A total of 18 patients will be enrolled.

Type d'étude

Interventionnel

Inscription (Estimé)

18

Phase

  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Lieux d'étude

  • Chine
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, Chine, 200025
        • Recrutement
        • Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
        • Contact:

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 75 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  • The patient or their legally authorized guardian has signed the informed consent form (ICF), indicating understanding of the purpose and procedures of this clinical trial and willingness to participate.

  • Age between 18 and 75 years, male or female.

  • Diagnosis of relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) according to the Chinese Guidelines for Diagnosis and Treatment of Adult Acute Lymphoblastic Leukemia (2024 edition).

  • Leukemic cells confirmed to express CD19 and/or CD22 by flow cytometry.

  • ECOG performance status 0-2.

  • Life expectancy ≥12 weeks.

  • Adequate organ function at screening, meeting all of the following laboratory criteria:

    1. Hematology: absolute neutrophil count (ANC) ≥1×10⁹/L; absolute lymphocyte count (ALC) ≥0.3×10⁹/L; platelet count ≥20×10⁹/L; hemoglobin ≥60 g/L.
    2. Hepatic function: ALT and AST ≤2.5× upper limit of normal (ULN); total bilirubin ≤1.5× ULN.
    3. Renal function: creatinine clearance (CrCl) ≥40 mL/min (by Cockcroft-Gault formula).
    4. Coagulation: fibrinogen ≥1.0 g/L; activated partial thromboplastin time (APTT) ≤1.5× ULN; prothrombin time (PT) ≤1.5× ULN.
    5. Oxygen saturation >91%.
    6. Left ventricular ejection fraction (LVEF) ≥50%.

  • The subject and their spouse agree to use effective contraceptive measures (excluding rhythm method) from ICF signing through 1 year after CAR-T cell infusion.

Exclusion Criteria:

  • Active graft-versus-host disease (GVHD) or autoimmune disease requiring long-term immunosuppressive therapy.
  • Use of therapeutic doses of corticosteroids (defined as prednisone or equivalent >20 mg/day) within 7 days prior to screening. Physiologic replacement, topical, and inhaled steroids are permitted.
  • Hypertension not controllable with medication.
  • Severe cardiac disease, including but not limited to: unstable angina, myocardial infarction (within 6 months prior to screening), congestive heart failure (NYHA class ≥III), or severe arrhythmia.
  • Unstable systemic disease as judged by the investigator, including but not limited to: severe hepatic, renal, or metabolic disease requiring medication.
  • Malignancy other than B-ALL within 5 years prior to screening, except for adequately treated carcinoma in situ of the cervix, basal cell or squamous cell skin cancer, localized prostate cancer after radical surgery, or ductal carcinoma in situ of the breast after radical surgery.
  • History of solid organ transplantation.
  • Planned surgery within 2 weeks after study treatment (subjects scheduled for local anesthesia surgery may participate).
  • Receipt of other interventional investigational drugs within 1 month prior to ICF signing.
  • Uncontrolled active infection.
  • Positive for HBsAg, or positive for HBcAb with detectable HBV DNA in peripheral blood; positive for HCV antibody with detectable HCV RNA; positive for HIV antibody; positive for CMV DNA; positive for syphilis serology.
  • Pregnant or breastfeeding women.
  • Psychiatric illness, consciousness disorder, or central nervous system disease.
  • Other conditions deemed unsuitable for enrollment by the investigator.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

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
Expérimental: Anti-CD19/CD22 Dual-Target Cord Blood CAR-T Cells

A single intravenous infusion of anti-CD19/CD22 dual-target umbilical cord blood-derived CAR-T cells administered on Day 0, following lymphodepleting chemotherapy with fludarabine (30 mg/m²/day) and cyclophosphamide (300 mg/m²/day) for three consecutive days. Dose escalation follows a 3+3 design across three dose levels (4.0×10⁶, 8.0×10⁶, and 12.0×10⁶ CAR-T/kg, ±20%). All subjects receive the same investigational product; no comparator arm is included.
Biologique: Anti-CD19/CD22 Dual-Target Cord Blood CAR-T Cells

Genetically modified umbilical cord blood-derived T cells expressing chimeric antigen receptors targeting both CD19 and CD22. Administered as a single intravenous infusion on Day 0 following lymphodepleting chemotherapy. Dose levels: 4.0×10⁶, 8.0×10⁶, and 12.0×10⁶ CAR-T/kg (±20%) according to 3+3 dose escalation design.

Médicament: Fludarabine

30 mg/m² intravenous infusion over 30 minutes once daily for 3 consecutive days as lymphodepleting preconditioning prior to CAR-T cell infusion.

Médicament: Cyclophosphamide

300 mg/m² intravenous infusion over 30 minutes once daily for 3 consecutive days as lymphodepleting preconditioning prior to CAR-T cell infusion.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Incidence and Severity of Dose-Limiting Toxicity (DLT)
Délai: Within 14 days after CAR-T cell infusion

DLT is defined as treatment-related adverse events occurring within 14 days post-infusion. Non-hematologic DLT: Grade ≥3 toxicity not reducible to ≤ Grade 1 within 72 hours. Hematologic DLT: Grade 4 toxicity (excluding lymphopenia) persisting >21 days, not attributable to underlying disease. Predefined exclusion criteria include tumor lysis syndrome, electrolyte disturbances, hypogammaglobulinemia, transient laboratory abnormalities, febrile neutropenia, and others per protocol. CRS/ICANS graded per ASTCT 2019, aGVHD per modified Glucksberg, other AEs per CTCAE v5.0.
Within 14 days after CAR-T cell infusion

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Objective Response Rate (ORR)
Délai: 1 and 3 months post-infusion

ORR is the proportion of subjects achieving CR/CRi at 1 and 3 months post-infusion. Efficacy assessed by bone marrow examination per international acute leukemia response criteria.
1 and 3 months post-infusion
Minimal Residual Disease (MRD) Negativity Rate
Délai: 1 and 3 months post-infusion

MRD negativity rate is the proportion of subjects achieving MRD-negative status by flow cytometry at 1 and 3 months post-infusion.
1 and 3 months post-infusion
Complete Remission (CR) Rate
Délai: 1 and 3 months post-infusion

CR rate is the proportion achieving CR. Efficacy assessed by bone marrow examination per international acute leukemia response criteria.
1 and 3 months post-infusion
Progression-Free Survival (PFS)
Délai: From infusion up to 24 months

PFS is defined as time from infusion to disease progression, relapse, or death. Median PFS and 12-/24-month PFS rates will be estimated by Kaplan-Meier method.
From infusion up to 24 months
Overall Survival (OS)
Délai: From infusion up to 24 months

OS is defined as time from infusion to death from any cause. Median OS and 12-/24-month OS rates will be estimated by Kaplan-Meier method.
From infusion up to 24 months
CAR-T Cell Expansion and Persistence
Délai: Up to 90 days post-infusion

CAR-T cell levels and vector copy number (VCN) in peripheral blood will be measured.
Up to 90 days post-infusion
CAR-T Cell Expansion and Persistence
Délai: Up to 90 days post-infusion

PK parameters: Cmax(Peak Plasma Concentration)
Up to 90 days post-infusion
CAR-T Cell Expansion and Persistence
Délai: Up to 90 days post-infusion

PK parameters: Tmax
Up to 90 days post-infusion
CAR-T Cell Expansion and Persistence
Délai: Up to 90 days post-infusion

PK parameters: AUC₀-₂₈d, AUC₀-₉₀d.
Up to 90 days post-infusion
CAR-T Cell Expansion and Persistence
Délai: At 3 and 6 months

Proportion of subjects with detectable CAR-T cells at 3 and 6 months, and duration of persistence will be recorded.
At 3 and 6 months

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Ruijin Hospital

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

13 mai 2026

Achèvement primaire (Estimé)

30 mars 2028

Achèvement de l'étude (Estimé)

30 mars 2028

Dates d'inscription aux études

Première soumission

26 juin 2026

Première soumission répondant aux critères de contrôle qualité

17 septembre 2026

Première publication (Réel)

24 septembre 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

25 septembre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

24 septembre 2026

Dernière vérification

1 septembre 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • RJ-ALL 2026-B01

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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