Nanobody-Based Anti-CD5 CAR-T for Relapsed/Refractory T-ALL/NHL

NCT06874946 | Recruiting Phase 1

• 1 other identifier: 2025PHD001-001
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

To observe the safety and efficacy of Nanobody-Based CD5-targeted chimeric antigen receptor T cells in the treatment of refractory or relapsed T-ALL/NHL

Conditions

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; T - Cell Lymphoma; PTCL

Keywords

CD5; R/R T-ALL/LBL; R/R PTCL

Outcome Measures

Primary Outcomes (2)

• DLT (Dose-Limiting Toxicity)

  CRS and ICANS will be assessed per ASTCT (2019), while other AEs follow CTCAE v5.0. DLTs are CAR-T-related AEs 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 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 (SRC).

  Day28 after CAR-T cell infusion

• Overall Response Rate (ORR)

  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) per European LeukemiaNet (ELN) 2022 for T-ALL and Lugano/Lyric 2016 for T-NHL. CR: \<5% blasts in bone marrow, no circulating blasts/extramedullary disease, ANC \>1.0 × 10⁹/L, platelets \>100 × 10⁹/L, MRD-negative. CRi: Meets CR but lacks full hematologic recovery. MLFS: \<5% blasts, no hematologic recovery required. Lugano 2016 (T-NHL): CR = complete metabolic response on PET-CT; PR = ≥50% tumor reduction.

  Within 3 months after CAR-T cell infusion

Secondary Outcomes (2)

• Progression-Free Survival (PFS)

  Within 2-year after CAR-T cell infusion

• Overall Survival (OS)

  Within 2-year after CAR-T cell infusion

Study Arms (1)

CD5-targeted CAR-T cells

EXPERIMENTAL

Eligible patients will receive a single infusion of CD5-targeted CAR-T cells at 3+3 dose-escalation design. Phase II: Patients will receive CD5-targeted CAR-T cells at the RP2D.

Biological: CD5-targeted CAR-T cells

Interventions

CD5-targeted CAR-T cells BIOLOGICAL

Phase I: Eligible patients will receive a single infusion of CD5-targeted CAR-T cells at one of three dose levels (0.5 × 10⁶ cells/kg, 1.0 × 10⁶ cells/kg, or 2.0 × 10⁶ cells/kg) following fludarabine and cyclophosphamide (FC) lymphodepleting chemotherapy. A 3+3 dose-escalation design will be used to determine the recommended Phase II dose (RP2D) based on safety, dose-limiting toxicities (DLTs), and preliminary efficacy. Phase II: Patients will receive CD5-targeted CAR-T cells at the RP2D following FC lymphodepleting chemotherapy.

CD5-targeted CAR-T cells

Eligibility Criteria

• Age: 3 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject or guardian understands and voluntarily signs the informed consent form (ICF).
• Male or female, aged 3-70 years at the time of signing the ICF (inclusive).
• Expected survival of at least 12 weeks.
• ECOG performance status of 0-2 at the time of ICF signing.
• Diagnosis of relapsed/refractory T-cell lymphoblastic leukemia/lymphoma (R/R T-ALL/NHL) confirmed at screening and meeting at least one of the following criteria:
• Bone marrow involvement: Morphologic examination shows ≥5% lymphoblasts, and/or
• Cerebrospinal fluid (CSF) involvement: Tumor cells detected in CSF, and/or
• Extramedullary disease: Presence of measurable lesions (lymph node/mass ≥1.5 cm in axial diameter or extranodal lesion ≥1 cm in axial diameter).
• CD5 expression: Tumor cells in bone marrow, peripheral blood, or CSF are CD5-positive by flow cytometry, and/or lymph node/mass or extranodal lesions are CD5-positive by pathology.
• Adequate major organ function, defined as:
• AST and ALT ≤5× upper limit of normal (ULN).
• Total bilirubin ≤2× ULN.
• Renal function: Serum creatinine clearance ≥60 mL/min (Cockcroft-Gault formula) or creatinine ≤1.5× ULN.
• Blood oxygen saturation \>92%.
• Reproductive health requirements:

You may not qualify if:

• 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
• Inflammatory bowel disease (IBD)

Sponsors & Collaborators

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

Study Sites (1)

Peking University People's Hospital

Beijing, Beijing Municipality, 100044, China

RECRUITING

MeSH Terms

Conditions

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, T-Cell

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; Lymphoma, Non-Hodgkin; Lymphoma

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: Deputy Hospital Director

Model Details: anti CD5 CAR-T cells, eligible patients will be treated with CD5-targeted CAR-T cells.

Study Record Dates

• First Submitted: March 8, 2025
• First Posted: March 13, 2025
• Study Start: February 14, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: May 7, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)