JWCAR201 for the Treatment of Hematology Malignancy and Autoimmune Diseases

An Open Label, Single Arm Study to Evaluate JWCAR201 Treating B Cell Driven Hematology Malignancy and Autoimmune Diseases

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

Study Overview

• Status: Not yet recruiting
• Conditions: Autoimmune Diseases; Lupus Erythematosus, Systemic; Large B-cell Lymphoma; B-cell Tumors
• Intervention / Treatment: Biological: JWCAR201

Detailed Description

JWCAR201 is a CD19/CD20 CAR-T product. By targeting both CD19 and CD20, it is expected to overcome some limitations with CD19 or CD20 single target products. In this study, patients with B cell driven hematology malignancy and autoimmune diseases will be enrolled to receive JWCAR201. PK/PD properties and preliminary efficacy and safety will be evaluated. Each subject will receive JWCAR201 once and is followed up for up to 2 years.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Liangjing Lu; Phone Number: 86-13661472001; Email: Lu_liangjing@163.com
• Study Contact Backup: Name: medical JW JW; Phone Number: +86 21 50464201; Email: Relma-celMedical@jwtherapeutics.com

Study Locations

• China
  • Shanghai, China, 200001
    • Renji Hospital, Shanghai Jiaotong University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

For subjects with B cell driven malignancy (relapsed/refractory large B cell lymphoma)

1. aged >= 18 years
2. willing to sign ICF
3. with histologically confirmed large B cell lymphoma and immunohistochemically positive CD20
4. The subject must have previously been treated with an anthracycline and rituximab (or another CD20-targeted therapy), and must have relapsed, not achieved remission, or experienced disease progression after receiving at least two lines of therapy, including autologous hematopoietic stem cell transplantation (autoHSCT)
5. The subject must have CT measurable lesions and PET evaluable lesions as determined by the Lugano criteria.
6. The subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

For subjects with SLE:

1. Voluntarily sign the informed consent form (ICF).
2. At the time of signing the ICF, be between 18 and 70 years old (inclusive of 18 and 70 years), with no restriction on gender.
3. Have been diagnosed with SLE (Systemic Lupus Erythematosus) for ≥ 6 months before screening, according to the 2019 EULAR/ACR revised criteria
4. Have previously required treatment with corticosteroids combined with immunosuppressants and biologics, with the treatment regimen stable for >2 months and the dose stable for >2 weeks before screening, yet the disease remains active.
5. At the time of screening, positive for antinuclear antibodies (ANA), and/or anti-dsDNA antibodies, and/or anti-Smith antibodies.

6. SLEDAI-2K score ≥ 7 points during the screening period.

   Exclusion Criteria:

   For subjects with B cell driven malignancy (relapsed/refractory large B cell lymphoma)

1. Primary central nervous system (CNS) lymphoma (subjects with secondary CNS lymphoma are allowed to enroll).

2. A history of another malignancy that has not been in complete remission for at least 2 years (the following conditions are exempt from the 2-year restriction: non-melanoma skin cancer, completely resected stage I tumors with a low likelihood of recurrence, treated localized prostate cancer, biopsy-confirmed in situ cervical cancer, or squamous intraepithelial lesions identified on a PAP smear).

3. At the time of screening, the subject has:

1. Hepatitis B surface antigen (HBsAg) positivity (regardless of whether or not there is an increase in hepatitis B virus DNA copies).
2. Hepatitis B core antibody (HBcAb) positivity with an increase in hepatitis B virus DNA copies.
3. Hepatitis C, HIV, or syphilis infection. 4. The subject has had active deep vein thrombosis (DVT) (tumor thrombus or blood clot) or pulmonary embolism (PE) within 3 months prior to signing the informed consent form.

5. The subject has been undergoing anticoagulant therapy for active DVT or PE within 3 months prior to signing the informed consent form (prophylactic treatment is excluded).

6. Uncontrolled systemic fungal, bacterial, viral, or other infections. 7. Acute or chronic graft-versus-host disease (GvHD). 8. History of any of the following cardiovascular diseases within the past 6 months: New York Heart Association (NYHA) Class III or IV heart failure, cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant heart diseases.

9. Clinically significant CNS diseases within the past 6 months or at the time of screening, such as epilepsy, seizures, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychiatric disorders.

10. Pregnant or breastfeeding women. Women of childbearing potential must have a negative serum pregnancy test within 48 hours prior to the start of lymphodepleting chemotherapy.

11. The investigator determines that the subject has any factors that could affect compliance with the protocol, including uncontrolled medical, psychological, familial, sociological, or geographical conditions; or the subject is unwilling or unable to comply with the procedures required by the study protocol.

12. The subject has previously received CAR-T cell therapy or other gene-modified T cell therapy.

For subjects with SLE:

1. Severe lupus nephritis requiring hemodialysis within 2 months before screening, or treatment with prednisone ≥ 100 mg/day or equivalent corticosteroids for ≥ 14 days.
2. Lupus crisis within 1 month before screening, deemed unsuitable for participation in this study by the investigator.
3. Clinically significant central nervous system disease or pathological changes not caused by lupus before screening, including but not limited to: cerebrovascular accident, aneurysm, epilepsy, seizures/convulsions, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis. Central nervous system manifestations caused by lupus before screening, including but not limited to lupus headache, seizures, cognitive impairment, intellectual disability, visual impairment, etc.
4. Concurrent other autoimmune diseases requiring systemic treatment.
5. History of major organ transplantation (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/bone marrow transplantation.
6. At the time of screening:

1)Active hepatitis B. 2)Hepatitis C, HIV, or syphilis infection. 7. History of any of the following cardiovascular diseases within 6 months before screening: New York Heart Association (NYHA) Class III or IV heart failure, myocardial infarction, unstable angina, uncontrolled or symptomatic atrial arrhythmias, any ventricular arrhythmias, or other clinically significant heart diseases.

8. Use of any other investigational drug for SLE within 1 month before screening. However, if the investigational treatment was ineffective or the disease relapsed during the study treatment period, and at least 3 half-lives of the drug have passed before screening, the patient may be eligible for enrollment.

9. Previous treatment with CAR-T cells or other gene-modified T cell therapies. 10. History of ≥ Grade 2 bleeding within 30 days before screening, or the need for long-term continuous use of anticoagulant medications (such as warfarin, low molecular weight heparin, or factor Xa inhibitors).

11. Undergoing plasmapheresis, plasma exchange, or hemodialysis within 14 days before screening.

12. Use of any live vaccines for infectious diseases within 1 month before screening.

13. Known life-threatening allergic reaction, hypersensitivity, or intolerance to JWCAR201 cell product or its excipients (including dimethyl sulfoxide (DMSO)).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JWCAR201 arm; Subjects in this arm will receive intervention with JWCAR201	Biological: JWCAR201; JWCAR201 is a autologous CAR-T targeting CD19/CD20

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Outcome Measure	Measure Description	Time Frame
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: Reduction in SLEDAI-2K Score by ≥ 4 Points:; No New BILAG A Scores, and No More Than 1 New BILAG B Score:; 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

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Collaborators: Shanghai Ming Ju Biotechnology Co., Ltd.
• Investigators: Principal Investigator: Liangjing Lu, Renji Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: August 15, 2024
• First Submitted That Met QC Criteria: August 19, 2024
• First Posted (Actual): August 22, 2024

Study Record Updates

• Last Update Posted (Actual): August 22, 2024
• Last Update Submitted That Met QC Criteria: August 19, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Autoimmune Diseases
• Other Study ID Numbers: JWCAR201001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No