An Exploratory Clinical Study of CD19 CAR NK Cell Injection for the Treatment of Relapsed/Refractory Autoimmune Diseases

Launched by CHANGHAI HOSPITAL · Jun 13, 2024

Keywords

ClinConnect Summary

This clinical trial is looking at a new treatment called CD19 CAR NK cell injection for people with autoimmune diseases that have not responded well to traditional therapies. The study aims to find out how safe and effective this treatment is by enrolling between 36 to 72 participants aged 18 to 65. To qualify, individuals must have specific autoimmune conditions, such as rheumatoid arthritis or systemic sclerosis, and their disease must still be active despite previous treatments.

Participants in the trial will receive the CD19 CAR NK cell injection, and researchers will closely monitor their health to see how well the treatment works and whether it causes any side effects. It’s important for potential participants to understand that they need to give their consent to join the study and will be required to follow certain guidelines, including using contraception if they are of childbearing age. This trial is currently recruiting, which means people can still sign up to participate if they meet the eligibility criteria.

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Eligibility criteria

• Common inclusion criteria:
• • 1. Age: ≥ 18 years old and ≤ 65 years old, male or female;
• 2. The functions of important organs meet the following requirements:
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• • 1. Bone marrow hematopoietic function needs to meet: a. White blood cell count ≥ 3 x 10\^9/L b. Neutrophil count ≥ 1 x 10\^9/L (no colony-stimulating factor treatment within 2 weeks before examination); c. Hemoglobin ≥60g/L;
• • 2. Liver function:ALT ≤ 3 x ULN,AST≤3 x ULN, TBIL≤1.5 x ULN(excluding Gilbert syndrome, total bilirubin ≤ 3.0 x ULN) (No requirements for conditions caused by the disease itself);
• • 3. Renal function: creatinine clearance rate (CrCl) ≥ 60 ml/minute(Cockcroft/Fault formula);
• • 4. Coagulation function: International standardized ratio (INR) \< 1.5 x ULN,prothrombin time(PT) \< 1.5 x ULN;
• • 5. Cardiac function: Good hemodynamic stability. 3. Female subjects of childbearing potential and male subjects whose partner is a female of childbearing potential are required to use medically approved contraception or abstain from sex for at least 6 months during and at least 6 months after the end of the study treatment period; female subjects of childbearing potential have had a negative serum HCG test within 7 days prior to study enrollment and are not lactating; 4. Voluntarily participate in this clinical study, sign an informed consent form, have good compliance, and cooperate with follow-up.
• Inclusion Criteria for Relapsing refractory dry syndrome:
• • 1. Meets 2002 AECG criteria or 2016 ACR/EULAR classification criteria for primary dry syndrome (pSS);
• • 2. Definition of disease activity: investigator-assessed disease ESSDAI score of 5 or higher;
• • 3. Ineffective conventional treatment or relapse of disease activity after remission. Definition of routine treatment: Use of glucocorticoids (above 1mg/Kg/d) and cyclophosphamide, as well as any of the following immunomodulatory drugs for more than 6 months: antimalarials, methotrexate, leflunomide, cyclophosphamide, azathioprine, mertiomate, tacrolimus, cyclosporine, and biologics, including rituximab, belimumab and tetracycline;
• Inclusion criteria for Systemic Sclerosis:
• • 1. Meets 2013 ACR classification criteria for systemic sclerosis;
• • 2. If combined with interstitial pneumonia, interstitial changes suggestive of ground-glass exudates on chest HRCT and FVC or DLCO \<70% predictive value on pulmonary function tests;
• • 3. Ineffective conventional treatment or relapse of disease activity after remission. Definition of routine treatment: Use of glucocorticoids (above 1mg/Kg/d) and cyclophosphamide, as well as any of the following immunomodulatory drugs for more than 6 months: antimalarials, methotrexate, leflunomide, cyclophosphamide, azathioprine, mertiomate, tacrolimus, cyclosporine, and biologics, including rituximab, belimumab and tetracycline;
• • 4. Definition of progressiveness; 1) Definition of cutaneous progression: increase in mRSS \>10%; 2) Definition of lung disease progression: 10% decrease in FVC or 5% decrease in FVC with 15% decrease in DLCO (OMERACT progression).
• Inclusion criteria for Recurrent refractory idiopathic inflammatory myopathy:
• • 1. Classification criteria for inflammatory myopathy in accordance with 2017 EULAR/ACR (including DM, PM, ASS, and NM);
• • 2. For those with muscle involvement, the MMT-8 score is lower than 142 and at least two abnormalities are found in the following five core measurements (PhGA, PtGA, or extramuscular disease activity score ≥ 2 points; total HAQ score ≥ 0.25; muscle enzyme levels are 1.5 times the upper limit of the normal range);
• • 3. Positive myositis antibodies;
• • 4. Ineffective conventional treatment or relapse of disease activity after remission. Definition of routine treatment: Use of glucocorticoids (above 1mg/Kg/d) and cyclophosphamide, as well as any of the following immunomodulatory drugs for more than 6 months: antimalarials, methotrexate, leflunomide, cyclophosphamide, azathioprine, mertiomate, tacrolimus, cyclosporine, and biologics, including rituximab, belimumab and tetracycline.
• Inclusion criteria for relapsing refractory rheumatoid arthritis:
• • 1. Meets the diagnostic criteria of the 2010 ACR/EULAR classification. Diagnosis of moderately or severely active rheumatoid arthritis with a previous diagnosis of rheumatoid arthritis ≥ 6 months;
• • 2. A swollen joint count of ≥ 6 (based on 66 joint counts) and a tender joint count of ≥ 6 (based on 68 joint counts) during the Screening Period;
• • 3. C-reactive protein (CRP) ≥ 10 mg/L or erythrocyte sedimentation rate (ESR) ≥ 28 mm/h during the Screening Period;
• 4. EULAR definition of refractory rheumatoid arthritis:
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• • 1. Failure of treatment according to EULAR recommended guidelines and failure of treatment with ≥2 b/tsDMARDs despite failure of treatment with csDMARDs. (i) unless treatment with bDMARDs/tsDMARDs is limited due to socioeconomic factors; and (ii) if treatment with csDMARDs is contraindicated, then failure of treatment with ≥2 b/tsDMARDs of different mechanisms also fulfills the condition);
• • 2. Symptom management of RA is considered problematic by both the patient and the physician;
• • 3. Signs suggestive of active or progressive disease if at least 1 of the following 5 items is met
• • 1. At least moderate disease activity (DAS28-ESR \>3.2 or CDAI \>10);
• • 2. Signs and/or symptoms suggestive of active disease;
• • 3. Inability to reduce glucocorticoids to less than 7.5 mg/day prednisone or equivalent;
• • 4. Rapid imaging progression (1-year increase of ≥5 points in van der Heijde modified Sharp score);
• • 5. Decreased quality of life due to RA, although RA is well controlled;
• • 6. Refractory rheumatoid arthritis is diagnosed if three of the above criteria are met.
• Common exclusion criteria:
• • 1. Subjects with known severe allergic reactions, hypersensitivity, contraindication to any medications during the trial (cyclophosphamide, fludarabine, tozumabs), or subjects with a history of severe allergic reactions; 2. Existence or suspicion of uncontrollable or treatable fungal, bacterial, viral or other infections; 3. Subjects with central nervous system disorders due to autoimmune diseases or non-autoimmune diseases(including epilepsy, psychosis, organic encephalopathy syndromes, cerebrovascular accidents, encephalitis, central nervous system vasculitis); 4. Subjects with relatively serious heart diseases, such as angina pectoris, myocardial infarction, heart failure, and arrhythmia; 5. Subjects with congenital immunodeficiency diseases; 6. Subjects with malignant tumors (except for non-melanoma skin cancer and in situ cervical, bladder, and breast cancers that have been disease-free for more than 5 years); 7. Subjects with end-stage renal failure; 8. Subjects with positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and HBV DNA titer in peripheral blood higher than the upper limit of detection; Patients with positive hepatitis C virus (HCV) antibodies and positive peripheral blood HCV RNA; People who are positive for human immunodeficiency virus (HIV) antibodies; Those who have tested positive for syphilis; 9. Subjects with mental illness and severe cognitive impairment; 10. Subjects who have received other clinical trial treatment within 3 months; 11. Pregnant or intending to conceive women; 12. In the opinion of the investigator, there are other reasons why subjects cannot be included in this study.
• Exclusion criteria for relapsing refractory dry syndrome:
• • 1. Combined cirrhosis of the liver;
• • 2. Combination of aplastic anemia (AA), myelodysplastic syndrome (MDS), or other myeloproliferative disease (MPD).
• Exclusion criteria for recurrent refractory idiopathic inflammatory myopathies:
• • 1. Drug-induced myositis;
• • 2. Inclusion body myositis;
• • 3. Tumor-associated myositis (myositis occurring within 2 years of tumor diagnosis).
• Exclusion criteria for relapsed refractory rheumatoid arthritis:
• • Functional status of rheumatoid arthritis graded at level 4 according to ACR.