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

NCT07838714 | Recruiting Phase 1

• 1 other identifier: RJ-ALL 2026-B01
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

B-cell Acute Lymphoblastic Leukemia

Keywords

Relapsed/refractory B-cell acute lymphoblastic leukemia; CAR-T cell; Umbilical cord blood

Outcome Measures

Primary Outcomes (1)

• Incidence and Severity of Dose-Limiting Toxicity (DLT)

  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

Secondary Outcomes (10)

• Objective Response Rate (ORR)

  1 and 3 months post-infusion

• Minimal Residual Disease (MRD) Negativity Rate

  1 and 3 months post-infusion

• Complete Remission (CR) Rate

  1 and 3 months post-infusion

• Progression-Free Survival (PFS)

  From infusion up to 24 months

• Overall Survival (OS)

  From infusion up to 24 months

Study Arms (1)

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

EXPERIMENTAL

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.

Biological: Anti-CD19/CD22 Dual-Target Cord Blood CAR-T Cells; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

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

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.

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

Fludarabine DRUG

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

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

Cyclophosphamide DRUG

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

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

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.
• Hepatic function: ALT and AST ≤2.5× upper limit of normal (ULN); total bilirubin ≤1.5× ULN.
• Renal function: creatinine clearance (CrCl) ≥40 mL/min (by Cockcroft-Gault formula).
• Coagulation: fibrinogen ≥1.0 g/L; activated partial thromboplastin time (APTT) ≤1.5× ULN; prothrombin time (PT) ≤1.5× ULN.
• Oxygen saturation \>91%.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

RECRUITING

MeSH Terms

Conditions

Burkitt Lymphoma

Interventions

fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Central Study Contacts

Weiyang Liu

CONTACT

+86 13817506393; lwy21758760@sjtu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chief physician, MD, PhD

Study Record Dates

• First Submitted: June 26, 2026
• First Posted: September 24, 2026
• Study Start: May 13, 2026
• Primary Completion (Estimated): March 30, 2028
• Study Completion (Estimated): March 30, 2028
• Last Updated: September 25, 2026

Record last verified: 2026-09

Locations

CN (1)