Nanobody-Based CD19/CD22 Tandem Dual CAR-T Therapy for R/R B-ALL

NCT06880913 | Recruiting Phase 1

• 1 other identifier: 2024PHD024-001
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the efficacy and safety of Nanobody-Based CD19/CD22 Tandem Dual Chimeric Antigen Receptor (CAR) T-cell therapy in patients with relapsed or refractory B-ALL

Conditions

Precursor B-Cell Lymphoblastic Leukemia-Lymphoma

Keywords

R/R B-ALL

Outcome Measures

Primary Outcomes (2)

• Dose-Limiting Toxicity (DLT)

  CRS and ICANS will be assessed per ASTCT (2019), while other AEs follow CTCAE v5.0. DLTs are CAR-T-related AEs (possibly, likely, or definitely related) that occur within 28 days post-infusion and meet the following criteria: Grade 4+ CRS, or Grade 3 CRS unresolved to ≤ Grade 2 within 7 days. Grade 3+ non-hematologic toxicity unresolved to ≤ Grade 2 within 7 days. Grade 4+ ICANS, or Grade 3 ICANS unresolved to ≤ Grade 2 within 3 days. Grade 4+ hematologic toxicity (excluding lymphopenia) lasting \>28 days. Grade 3+ hypersensitivity reaction. Any unexpected toxicity requiring study discontinuation. Exemptions: Rapid hypersensitivity resolving to ≤ Grade 2 in 2 hours. Reversible Grade 3 AEs lasting ≤7 days. Transient CRS-related organ dysfunction, resolving in ≤7 days per SRC. All DLTs are reviewed by the Safety Review Committee.

  Day28 after CAR-T cell infusion

• Overall Response Rate (ORR)

  Time Frame: Within 3 months after CAR-T cell infusion Definition: ORR is defined as the proportion of patients achieving complete remission (CR), complete remission with incomplete hematologic recovery (CRi), or morphologic leukemia-free state (MLFS), as per European LeukemiaNet (ELN) 2022 criteria. Response Criteria (ELN 2022): Complete Remission (CR): \<5% bone marrow blasts Absolute neutrophil count (ANC) ≥1.0 × 10⁹/L Platelet count ≥100 × 10⁹/L No evidence of extramedullary disease Full hematologic recovery Complete Remission with Incomplete Hematologic Recovery (CRi): \<5% bone marrow blasts ANC \<1.0 × 10⁹/L and/or platelet count \<100 × 10⁹/L No evidence of extramedullary disease Morphologic Leukemia-Free State (MLFS): \<5% bone marrow blasts No hematologic recovery required (ANC and platelet counts may remain low) No extramedullary leukemia

  Within 3 months after CAR-T cell infusion

Secondary Outcomes (2)

• Disease-Free Survival (DFS)

  2-year

• Overall Survival (OS)

  2-year

Study Arms (1)

CD19/CD22 Tandem Dual CAR-T

EXPERIMENTAL

Eligible patients will be treated with Nanobody-Based CD19/CD22 Tandem Dual CAR-T

Biological: Nanobody-Based CD19/CD22 Tandem Dual CAR-T

Interventions

Nanobody-Based CD19/CD22 Tandem Dual CAR-T BIOLOGICAL

Phase I: Patients will receive a single infusion of autologous CD19/CD22 dual CAR-T cells at one of three dose levels (0.3 × 10⁶ cells/kg, 1.0 × 10⁶ cells/kg, or 2.0 × 10⁶ cells/kg) following fludarabine (25-30mg/m2\*3d) and cyclophosphamide (250-300mg/m2\*3d) (FC) lymphodepleting chemotherapy. Phase II: Patients will receive autologous CD19/CD22 dual CAR-T cells at the RP2D following FC lymphodepleting chemotherapy.

CD19/CD22 Tandem Dual CAR-T

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject or their legally authorized representative (guardian) understands the study and voluntarily signs the informed consent form (ICF).
• Male or female, aged 12 to 65 years at the time of signing the ICF (inclusive of the cutoff values).
• Expected survival of at least 12 weeks. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at the time of signing the ICF.
• At the time of signing the ICF, the patient must be diagnosed with R/R B-ALL and meet the following criteria:
• Bone marrow morphological examination at screening shows \>5% blasts in the bone marrow, and/or cerebrospinal fluid (CSF) analysis detects leukemic cells, and/or the presence of measurable extramedullary lesions, defined as:
• Any lymph node or mass with an axial diameter \>1.5 cm Any extranodal lesion with an axial diameter \>1.0 cm
• Flow cytometry confirms CD19 or CD22 positivity in tumor cells from bone marrow, peripheral blood, or cerebrospinal fluid, or pathology confirms CD19 or CD22 positivity in lymph nodes/masses or extranodal lesions.
• Eligibility for Phase II (RP2D) is restricted to patients with R/R B-ALL who have failed prior immunotherapies, including blinatumomab, inotuzumab ozogamicin, or prior single-target CAR-T therapy.
• Adequate organ function, meeting the following laboratory criteria:
• Liver function:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5× upper limit of normal (ULN) Total bilirubin ≤2× ULN
• Renal function:
• Adults: Serum creatinine clearance ≥60 mL/min (using the Cockcroft-Gault formula) or creatinine ≤1.5× ULN
• Children: Serum creatinine levels must not exceed the following values:
• years: ≤1.2 mg/dL Males 13-16 years: ≤1.5 mg/dL Females ≥13 years: ≤1.4 mg/dL Males ≥16 years: ≤1.7 mg/dL Blood oxygen saturation (SpO₂) \>92% on room air. Fertile male and female subjects of reproductive potential must agree to use effective contraception from the time of informed consent until 2 years after administration of the study drug.

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from the study:
• History of central nervous system (CNS) diseases, including but not limited to:
• Epilepsy
• Paralysis
• Aphasia
• Stroke
• Severe brain injury
• Dementia
• Parkinson's disease
• Neuropathy
• History of autoimmune diseases requiring systemic immunosuppressive therapy within 2 years prior to signing the ICF, including but not limited to:
• Crohn's disease
• Rheumatoid arthritis
• Systemic lupus erythematosus (SLE)
• Systemic sclerosis

Sponsors & Collaborators

• Peking University People's Hospital: lead
• Hebei Senlang Biotechnology Inc., Ltd.: collaborator

Study Sites (1)

Deparment of Hematology, Peking University People's Hospital

Beijing, Beijing Municipality, 100044, China

RECRUITING

MeSH Terms

Conditions

Precursor B-Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Xiao-jun Huang, MD

  Peking University People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

MENG LV, MD, PhD

CONTACT

+861088324637; drlvmeng@bjmu.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: Director of Peking University Institute of Hematology

Model Details: Phase I, a traditional 3+3 dose-escalation design and determine the recommended Phase II dose; Phase II, a single-arm, open-label study design.

Study Record Dates

• First Submitted: March 8, 2025
• First Posted: March 18, 2025
• Study Start: November 14, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: March 30, 2026

Record last verified: 2026-03

Locations

CN (1)