T-ALL/Lymphoma
Conditions
Keywords
T-ALL, T-LBL, PTCL-NOS, AITL, ALCL, ENKL, T-PLL, ATLL, MF/SS
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.
Detailed description
This study is a single-arm, open-label, dose-finding and expansion clinical trial aimed at evaluating the safety and efficacy of anti-CD5 CAR-NK therapy for the treatment of patients with relapsed/refractory T-Cell hematologic malignancies. The goal is to determine the recommended dose of CAR-NK cell therapy for these conditions. The study includes three dose groups: 1×10⁷ CAR-positive cells/kg, 3×10⁷ CAR-positive cells/kg, and 5×10⁷ CAR-positive cells/kg. 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. The investigaors have the flexibility to adjust the second infusion dose based on the subject's condition.
Interventions
BIOLOGICALAnti-CD5 CAR NK cells
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.
Sponsors
Chongqing Precision Biotech Co., Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
\- 1.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: 1. 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: 1. Refractory to ≥2 cycles of standard induction chemotherapy (failure to achieve CR). 2. Relapsed within 12 months after achieving CR with first-line induction therapy. 3. Failure to achieve CR or relapse after ≥2 lines of chemotherapy. 4. Relapse after hematopoietic stem cell transplantation (HSCT). 2. 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: 1. 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. 2. Refractory to ≥2 lines of chemotherapy, primary resistance, or relapse post-HSCT. 3.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). 4.ECOG Performance Status: 0-2 . 5.Life Expectancy: ≥12 weeks. 6.Organ Function: <!-- --> 1. Cardiac: Left ventricular ejection fraction (LVEF) ≥50% by echocardiography; no significant ECG abnormalities. 2. Renal: Serum creatinine ≤2.0×ULN. 3. Hepatic: ALT/AST ≤3.0×ULN (≤5.0×ULN if liver involvement); total bilirubin ≤2.0×ULN. 4. Pulmonary: Oxygen saturation ≥92% (room air). 7.No Contraindications: To leukapheresis, venipuncture, or cell collection. 8.No Severe Psychiatric Disorders. 9.Contraception: Agreement to use effective contraception from informed consent until 1 year post-CAR-NK infusion (for patients of childbearing potential). 10.Informed Consent: Signed by the patient or legal guardian, confirming understanding of the trial's purpose and procedures.
Exclusion criteria
1. Prior CAR-NK therapy or genetically modified cell therapy. 2. Active CNS involvement at screening (prior CNS involvement with resolved status post-treatment is allowed). 3. Recent Anticancer Therapy: 1. Chemotherapy, targeted therapy, or investigational drugs within 2 weeks or 5 half-lives prior to screening. 2. Radiotherapy within 2 weeks prior to screening. 4. Active/Uncontrolled Infection: Within 1 week prior to screening. 5. Cerebrovascular Event or Seizure: Within 6 months prior to screening. 6. Viral Infections: 1. HBV DNA \> ULN (if HBsAg+ or HBcAb+). 2. HCV RNA \> ULN (if HCV Ab+). 3. HIV+, syphilis+, or active tuberculosis. 7. Cardiac Disease: 1. NYHA Class III/IV congestive heart failure. 2. Myocardial infarction or CABG ≤6 months prior. 3. Clinically significant ventricular arrhythmia or unexplained syncope (excluding vasovagal/dehydration-related). 4. Severe cardiomyopathy. 8. Active/Uncontrolled Autoimmune Disease. 9. Prior Malignancy: Within 5 years, except for cured cervical carcinoma in situ, basal/squamous skin cancer, localized prostate cancer, or ductal carcinoma in situ. 10. Live Vaccination: Within 4 weeks prior to screening. 11. Pregnancy/Lactation: Pregnant, breastfeeding, or planning pregnancy within 1 year post-CAR-NK infusion. 12. Other: Investigator-determined ineligibility.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free-Survival (PFS) after CAR-NK infusion | 2 years | PFS is the time from CAR-NK cell infusion to disease progression or death from any cause, capturing both tumor control and survival outcomes |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | 28 dyas | The incidence of adverse events after CAR-NK cell infusion was assessed by CTCAE, version 5.0. |
| Objective response rate (ORR) | 1month, 2 months, 3 months | 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). |
| Overall survival (OS) after CAR-NK infusion | 2 years | 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. |
| Duration of response (DOR) after CAR-NK infusion | 2 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To obtain the cytodynamics data of CAR-NK cells in vivo【pharmacodynamics】 | 3months | The content of free IL-6 in peripheral blood at each time point after transfusion was determined by immunohistochemical method |
| To obtain the cytodynamics data of CAR-NK cells in vivo【pharmacokinetics】 | 3months | Cmax:The highest concentration of CAR T cells amplified in peripheral blood after reinfusion |
Countries
China
Contacts
Primary ContactJia Wei, MD
Outcome results
None listed