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

NCT ID: NCT06631040

Last Updated: 2024-10-08

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-19
• Study Completion Date: 2026-12-30

Brief 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.

Conditions

Acute Lymphocytic Leukemia in Relapse

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Acute lymphocytic leukemia, in relapse

Group Type: EXPERIMENTAL

anti CD19 CAR NK cells

Intervention Type: BIOLOGICAL

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.

Interventions

anti CD19 CAR NK cells

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.

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 3 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Shahid Beheshti University of Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

Masoud Soleimani

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Shahid Ghazi Hospital, Tabriz university of medical sciences

Tabriz, , Iran

Countries

Iran

Facility Contacts

Masoud Soleimani

Role: primary

soleimani.masoud@gmail.com

09122875993

Other Identifiers

75358

Identifier Type: -

Identifier Source: org_study_id