Cell Therapy with Anti-CD19 CAR-NK Cells in Patients with Relapsed or Resistant B-ALL

Trial Title: Cell Therapy with Anti-CD19 CAR-NK Cells in Patients with Relapsed or Resistant B-ALL

NCT ID: NCT06631040

Condition: Acute Lymphocytic Leukemia in Relapse

Conditions: Official terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma

Conditions: Keywords:
CAR-NK Therapy
anti-CD19

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Biological
Intervention name: anti CD19 CAR NK cells
Description: Ten eligible patients with relapsed Acute Lymphoblastic Leukemia will be enrolled based on inclusion criteria and informed consent. After conditioning with Fludarabine and Cyclophosphamide, patients will receive a single infusion of anti-CD19 CAR NK cells with close monitoring using one of the following dose levels: • Dose Level 1: 1×10^7/Kg • Dose Level 2: 5×10^7/Kg • Dose Level 3: 1×10^8/Kg Safety Assessment: Adverse events will be recorded and graded. Laboratory parameters and cytokine release syndrome (CRS) markers will be closely monitored. Efficacy Evaluation: Response assessments will follow International Lymphoma Party (LWP) Group guidelines, including complete response (CR), partial response (PR), stable disease (SD), and progressive disease.
Arm group label: Acute lymphocytic leukemia, in relapse

Summary: Immunotherapy has shown promise in treating hematological malignancies, including resistant B-ALL. One approach is CAR-NK cell therapy, which involves genetically modifying natural killer (NK) cells to target specific cancer antigens. While CAR-NK therapy offers advantages over CAR-T therapy, such as reduced immune system reactions and lower production time and cost, challenges remain regarding antitumor efficacy and the tumor microenvironment. Preclinical and early clinical studies have targeted various antigens, including CD19, with CAR-NK cells in resistant B-ALL. To further investigate the potential of anti-CD19 CAR-NK cell therapy, this study aims to evaluate its safety and determine the maximum tolerated dose (MTD) in patients who have not responded to standard treatment.

Criteria for eligibility:
Criteria:
Inclusion Criteria: Eligible diseases: Acute lymphocytic leukemia (ALL CD19+). Patients 3 years of age or older, and must have a life expectancy > 12 weeks. Eastern cooperative oncology group (ECOG) performance status of 0-2 or karnofsky performance status (KPS) score is higher than 60. Females of child-bearing potential must have a negative pregnancy test and all subjects must agree to use an effective method of contraception for up to two weeks after the last infusion of CAR NK cells. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements: White blood cell count (WBC) ≥ 2500c/ml, Platelets ≥ 50×10^9/L, Hb ≥ 9.0g/dL, lymphocyte (LY) ≥ 0.7×10^9/L, LY% ≥ 15%, Alb ≥ 2.8g/dL, serum lipase and amylase < 1.5×upper limit of normal, serum creatinine ≤ 2.5mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5×upper limit of normal, serum total bilirubin ≤ 2.0mg/dL. These tests must be conducted within 7 days prior to registration. Ability to give informed consent. Exclusion Criteria: Pregnant or nursing women may not participate. Active HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at the time of screening. Serious illness or medical condition which would not permit the patient to be managed according to the protocol, including active uncontrolled infection, major cardiovascular, coagulation disorders, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive/restrictive pulmonary disease, or psychiatric or emotional disorders. History of severe immediate hypersensitivity to any of the agents including cyclophosphamide, fludarabine, or aldesleukin. Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary. The existence of unstable or active ulcers or gastrointestinal bleeding. Patients need anticoagulant therapy (such as warfarin or heparin). Patients need long-term antiplatelet therapy (aspirin at a dose > 300mg/d; clopidogrel at a dose > 75mg/d). Patients using fludarabine or cladribine chemotherapy within 3 months prior to leukapheresis.

Gender: All

Minimum age: 3 Years

Maximum age: N/A

Healthy volunteers: Accepts Healthy Volunteers

Locations:

Facility:
Name: Shahid Ghazi Hospital, Tabriz university of medical sciences

Address:
City: Tabriz
Country: Iran, Islamic Republic of

Contact:
Last name: Masoud Soleimani

Phone: 09122875993
Email: soleimani.masoud@gmail.com

Start date: December 19, 2024

Completion date: December 30, 2026

Lead sponsor:
Agency: Shahid Beheshti University of Medical Sciences
Agency class: Other

Source: Shahid Beheshti University of Medical Sciences

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06631040