Clinical trial NCT06631040: Cell Therapy with Anti-CD19 CAR-NK Cells in Patients with Relapsed or Resistant B-ALL
Official title: Cell Therapy with Anti-CD19 CAR-NK Cells in Patients with Relapsed or Resistant B-Acute Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Acute Lymphocytic Leukemia in Relapse
Keywords: CAR-NK Therapy
anti-CD19
Lead sponsor: Shahid Beheshti University of Medical Sciences
Sponsor class: OTHER
First posted: 2024-10-08
Enrollment: 10
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Incidence of dose-limiting toxicity (DLTs)
timeFrame: 4 weeks
measure: Assessment of Maximum Tolerated Dose (MTD)
timeFrame: 4 weeks
measure: Overall Remission Rate (ORR)
timeFrame: 8 weeks
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: 48 weeks
measure: Duration of Response (DOR)
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Tabriz
country: Iran, Islamic Republic of
facility: Shahid Ghazi Hospital, Tabriz university of medical sciences
Study officials:
References: