Clinical Trial of CD5-targeted CAR-NK Therapy for Relapse/Refractory T-Cell Hematologic Malignancies

NCT06909474 | Recruiting Phase 1

• 1 other identifier: PBC083
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is a clincal trial initiated by investigator to evaluate the safety and efficacy of anti-CD5 CAR-NK in the treatment of patients with relapsed/refractory T-Cell hematologic malignancies.

Conditions

T-ALL/Lymphoma

Keywords

T-ALL; T-LBL; PTCL-NOS; AITL; ALCL; ENKL; T-PLL; ATLL; MF/SS

Outcome Measures

Primary Outcomes (5)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  The incidence of adverse events after CAR-NK cell infusion was assessed by CTCAE, version 5.0.

  28 dyas

• Objective response rate (ORR)

  Objective Response Rate (ORR) within 3 Months: 1. For patients with T-cell lymphoma, ORR includes complete response (CR) and partial response (PR); 2. For patients with T-cell acute lymphoblastic leukemia (T-ALL), ORR includes CR, CR with partial hematologic recovery (CRh), CR with incomplete hematologic recovery (CRi), and morphologic leukemia-free state (MLFS).

  1month, 2 months, 3 months

• Overall survival (OS) after CAR-NK infusion

  OS is defined as the time from CAR-NK cell infusion to death from any cause, reflecting the long-term survival benefit of the therapy.

  2 years

• Duration of response (DOR) after CAR-NK infusion

  DOR measures the time from the first achievement of objective response to disease progression or death, evaluating the durability of treatment efficacy in responding patients.

  2 years

• Progression-Free-Survival (PFS) after CAR-NK infusion

  PFS is the time from CAR-NK cell infusion to disease progression or death from any cause, capturing both tumor control and survival outcomes

  2 years

Secondary Outcomes (3)

• To obtain the cytodynamics data of CAR-NK cells in vivo【pharmacokinetics】

  3months

• To obtain the cytodynamics data of CAR-NK cells in vivo【pharmacokinetics】

  3months

• To obtain the cytodynamics data of CAR-NK cells in vivo【pharmacodynamics】

  3months

Study Arms (1)

CD5 CAR-NK cells

EXPERIMENTAL

Biological: Anti-CD5 CAR NK cells

Interventions

Anti-CD5 CAR NK cells BIOLOGICAL

Each patient will initially receive a single infusion of CAR-NK cells on Day 0. If a suboptimal response is observed after the first infusion (assessed by Day 28) and the safety profile remains acceptable, a second infusion may be administered as a remedial dose after Day 28. CAR-NK cells need to be controlled within 70 minutes from thawing to infusion completion.

CD5 CAR-NK 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:

• Gender and Age: No gender restriction; age 18-75 years (inclusive). 2.Diagnosis: Confirmed diagnosis of T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoma, including:
• T-ALL Patients: Bone marrow morphology during screening shows ≥5% blasts/immature lymphocytes and/or flow cytometry confirms minimal residual disease (MRD)+, and meets any of the following:
• Refractory to ≥2 cycles of standard induction chemotherapy (failure to achieve CR).
• Relapsed within 12 months after achieving CR with first-line induction therapy.
• Failure to achieve CR or relapse after ≥2 lines of chemotherapy.
• Relapse after hematopoietic stem cell transplantation (HSCT).
• T-cell Lymphoma Patients: Confirmed diagnosis of T-lymphoblastic lymphoma (T-LBL) or T-cell non-Hodgkin lymphoma (including but not limited to: peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL), extranodal NK/T-cell lymphoma (ENKL), T-cell prolymphocytic leukemia (T-PLL), adult T-cell leukemia/lymphoma (ATLL), mycosis fungoides/Sézary syndrome (MF/SS) stage IIB or higher), and meets both:
• At least one bidimensionally measurable lesion per Lugano 2014 criteria: nodal lesions \>1.5 cm in long axis; extranodal lesions \>1.0 cm in long axis.
• Refractory to ≥2 lines of chemotherapy, primary resistance, or relapse post-HSCT.
• CD5 Positivity: Confirmed by flow cytometry (≥80% tumor cells express CD5 with mean fluorescence intensity \[MFI\] equivalent to normal T cells; Dim defined as MFI ≥1 log lower than normal T cells; partial positivity defined as 20-80% tumor cells expressing CD5) or immunohistochemistry (\>30% tumor cells express CD5).
• ECOG Performance Status: 0-2 . 5.Life Expectancy: ≥12 weeks. 6.Organ Function:
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• Cardiac: Left ventricular ejection fraction (LVEF) ≥50% by echocardiography; no significant ECG abnormalities.
• Renal: Serum creatinine ≤2.0×ULN.
• Hepatic: ALT/AST ≤3.0×ULN (≤5.0×ULN if liver involvement); total bilirubin ≤2.0×ULN.

You may not qualify if:

• Prior CAR-NK therapy or genetically modified cell therapy.
• Active CNS involvement at screening (prior CNS involvement with resolved status post-treatment is allowed).
• Recent Anticancer Therapy:
• Chemotherapy, targeted therapy, or investigational drugs within 2 weeks or 5 half-lives prior to screening.
• Radiotherapy within 2 weeks prior to screening.
• Active/Uncontrolled Infection: Within 1 week prior to screening.
• Cerebrovascular Event or Seizure: Within 6 months prior to screening.
• Viral Infections:
• HBV DNA \> ULN (if HBsAg+ or HBcAb+).
• HCV RNA \> ULN (if HCV Ab+).
• HIV+, syphilis+, or active tuberculosis.
• Cardiac Disease:
• NYHA Class III/IV congestive heart failure.
• Myocardial infarction or CABG ≤6 months prior.
• Clinically significant ventricular arrhythmia or unexplained syncope (excluding vasovagal/dehydration-related).

Sponsors & Collaborators

• Chongqing Precision Biotech Co., Ltd: lead

Study Sites (1)

Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology

Wuhan, Hubei, 430030, China

RECRUITING

MeSH Terms

Conditions

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

Central Study Contacts

Jia Wei, MD

CONTACT

+86 13986102084; jiawei@tjh.tjmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2025
• First Posted: April 3, 2025
• Study Start: March 27, 2025
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2028
• Last Updated: April 3, 2025

Record last verified: 2025-03

Locations

CN (1)