JWCAR201 for the Treatment of Hematology Malignancy and Autoimmune Diseases
NCT Number: NCT06567080
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: B-cell Tumors|Autoimmune Diseases|Lupus Erythematosus, Systemic|Large B-cell Lymphoma
Interventions: BIOLOGICAL: JWCAR201
Sponsor: RenJi Hospital
Collaborators: Shanghai Ming Ju Biotechnology Co., Ltd.
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 15
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09
Completion Date: 2027-03
Locations: Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200001, China

Summary:
JWCAR201 is a CD19/CD20 CAR-T product. This trial is intended to evaluate the safety, PK/PD and efficacy of JWCAR201 in patients with B cell driven hematology malignancy and autoimmune diseases

Primary Outcome Measures: the rate of Dose Limiting Toxicity events, Dose-Limiting Toxicity (DLT) refers to a specific type of adverse effect or toxic reaction caused by a drug or treatment that is severe enough to prevent an increase in dose or continuation of treatment., 28 days|the rate of AE and SAE, any adverse event (AE) or serious adverse event (SAE) occurring after JWCAR201 administration, up to 2 years
Secondary Outcome Measures: the change of number of JWCAR201 cells by measuring the cell number and the number of transgene copies over time, to evaluate PK properties of JWCAR201, that is, how the human body processes the infused JWCAR201 cells, from baseline up to 2 years|the change of numbers of B cell subtypes (e.g., CD19+, CD20+ B cells) in the blood, these are parameters to evaluate PD properties of JWCAR201, from baseline up to 2 years|overall response rate (ORR) in subjects with hematology malignancy, ORR is the proportion of subjects who achieve positive response to the treatment. It includes complete response and partial response., from baseline up to 2 years|complete response rate (CRR) in subjects with hematology malignancy, CRR refers to the proportion of subjects whose cancer signs disappear, from baseline up to 2 years|duration of response in subjects with hematology malignancy, The duration of a subject staying in response state, from baseline up to 2 years|progression free survival in subjects with hematology malignancy, the length of time during and after treatment that a subject lives with the disease without the disease worsening or progressing, from baseline up to 2 years|Overall survival in subjects with hematology malignancy, the length of time from the start of treatment that patients are still alive, from baseline up to 2 years|the proportion of subjects achieving LLDAS in subjects with SLE, Lupus Low Disease Activity State (LLDAS) is a target for treatment, representing a state where the disease is under control to a degree that is considered acceptable for the patient's long-term health and well-being. It includes below requirements: (1) SLE Disease Activity Index (SLEDAI)-2K ≤4, with no activity in major organ systems (renal, central nervous system (CNS), cardiopulmonary, vasculitis, fever) and no haemolytic anaemia or gastrointestinal activity; (2) no new lupus disease activity compared with the previous assessment; (3) a Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI physician global assessment (scale 0-3) ≤1; (4) a current prednisolone (or equivalent) dose ≤7.5 mg daily; and (5) well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents., from baseline up to 2 years|the proportion of subjects achieving DORIS in subjects with SLE, Definitions of Remission in SLE (DORIS) is considered an optimal treatment goal, indicating that the disease is inactive and that the patient has minimal or no symptoms. DORIS includes below requirements: clinical systemic lupus erythematosus disease activity index (SLEDAI)-2K=0, Evaluator's Global Assessment \<0.5 (0-3), prednisolone 5 mg/day or less, and stable antimalarials, immunosuppressives, and biologics., from baseline up to 2 years|the proportion of subjects achieving SRI-4 in subjects with SLE, Systemic Lupus Erythematosus Responder Index-4 (SRI-4) is a composite index used in clinical trials to assess the effectiveness of treatments for SLE. To be considered a responder according to SRI-4, a patient must meet the following criteria:

1. Reduction in SLEDAI-2K Score by ≥ 4 Points:
2. No New BILAG A Scores, and No More Than 1 New BILAG B Score:
3. No Worsening in Physician's Global Assessment (PGA):, from baseline up to 2 years|the change of BILAG-2004 score in subjects with SLE, British Isles Lupus Assessment Group (BILAG)-2004 is a score designed to evaluate lupus disease activity across nine organ system. For each organ system, disease activity is assessed and categorized into one of five levels:

A (Severe Activity): High disease activity requiring significant treatment, such as starting or increasing high-dose immunosuppressive therapy or biologics.

B (Moderate Activity): Moderate disease activity that might require an increase in treatment, such as adding or increasing corticosteroids or other immunosuppressive drugs.

C (Mild Activity): Mild disease activity that might not require a change in current treatment.

D (No Current Activity but Presence of Past Disease): The patient has no current disease activity, but there is evidence of past disease involvement in that organ system.

E (No Current or Past Activity): The patient has no current or past disease activity in that organ system., from baseline up to 2 years|the change of Physician's global assessment (PGA) score in subjects with SLE, PGA is a subjective measure where the physician evaluates and rates the patient's disease activity based on their clinical judgment, considering all aspects of the disease, ranging from 0 to 3. The higher the score, the more severe the disease activity., from baseline up to 2 years|the change of SLE-DAS score in subjects with SLE, Systemic Lupus Erythematosus-Disease Activity Score (SLE-DAS) is a validated, continuous measure of disease activity in patients with Systemic Lupus Erythematosus, typically ranging from 0 to over 20. The higher the score, the more active the disease., from baseline up to 2 years|the proportion of subjects without other SLE therapies, If JWCAR201 works well, subjects would not need other SLE therapies, from baseline up to 2 years|The change of fatigue score in subjects with SLE, Fatigue is one of the common symptoms of SLE subjects. A numerical rating scale ranging from 0-10 will be used to assess fatigue, the higher the score, the more severe the fatigue., from baseline up to 2 years|The change from baseline in immunoglobulins (IgA, IgE, IgG, IgM), JWCAR201 can deplete B cells, thus decrease the concentration of immunoglobulins, which are produced by B cells., from baseline up to 2 years|the change from baseline in complements (C3, C4), Complement levels, C3 and C4, increase in active SLE and will decrease following effective treatment, from baseline up to 2 years|The change from baseline in auto-antibodies (anti-dsDNA antibody, ANA), anti-dsDNA and ANA antibodies are auto-reactive antibodies produced by pathogenic B cells. JWCAR201 can deplete pathogenic B cells and decrease concentration of the auto-antibodies, indicating the improvement of SLE., from baseline up to 2 years