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The purpose of this study is to evaluate the safety and tolerability of P-CD19CD20-ALLO1 in participants with highly active, severe, refractory SLE with or without lupus nephritis (LN). This study includes a dose-escalation stage followed by an expansion stage. It will also evaluate the cellular kinetics (CK), pharmacodynamics (PD), and efficacy of P-CD19CD20-ALLO1.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose Escalation | Experimental | Participants with SLE (with or without LN) will receive the following interventions and dose escalated per protocol: Biological: P-CD19CD20-ALLO1 Drug: Cyclophosphamide Drug: Fludarabine Drug: Rimiducid |
|
| Dose Expansion (LN cohort) | Experimental | Participants with SLE (with LN) will receive the following interventions at or below the maximum tolerated dose (MTD), as determined in the dose escalation stage per protocol: Biological: P-CD19CD20-ALLO1 Drug: Cyclophosphamide Drug: Fludarabine Drug: Rimiducid |
|
| Dose Expansion (ERL cohort) | Experimental | Participants with SLE (with ERL) will receive the following interventions at or below the maximum tolerated dose (MTD), as determined in the dose escalation stage per protocol: Biological: P-CD19CD20-ALLO1 Drug: Cyclophosphamide Drug: Fludarabine Drug: Rimiducid |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| P-CD19CD20-ALLO1 Cells | Biological | P-CD19CD20-ALLO1 cells will be administered intravenously as per the schedule specified in the protocol. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Dose-limiting Toxicities (DLTs) at Each Dose Level of P-CD19CD20-ALLO1 | Day 1 up to Day 29 | |
| Number of Participants With Adverse Events (AEs) | Up to 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Chimeric Antigen Receptor (CAR) Transgene Copies in Blood Assessed by Droplet Digital Polymerase Chain Reaction (ddPCR) | Up to 5 years | |
| B-cell Levels in the Blood | Up to 5 years | |
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Key Inclusion criteria:
18-75 years old
SLE diagnosis per 2019 EULAR/ACR classification criteria ≥ 24 weeks
Autoantibody positive and low complement at screening
Treatment refractory: Failed ≥ 2 treatments for at least 3 months
Highly active disease:
SLEDAI-2K ≥ 8 (excluding alopecia, headache, and fever; additional protocol-specified requirements to enhance specificity of findings)
BILAG-2004 cat A in ≥ 1 organ system and/or cat B in ≥ 2 organ systems (excluding constitutional, musculoskeletal, and/or mucocutaneous organ systems for category B)
PGA score ≥ 1.0 on a 0 to 3 VAS
For patients with lupus nephritis:
Biopsy-proven Class III or IV (± Class V) active LN per 2018 ISN/RPS criteria within 12 months of screening
Modified NIH activity index ≥ 1/24
UPCR ≥ 1g/g
Key Exclusion criteria:
Participants who are pregnant, breastfeeding, or intend to become pregnant within the timeframe in which contraception is required
Prior treatment with CAR T-cell therapy, B-cell-targeting T-cell-dependent bispecific antibody, gene therapy product, total body irradiation, allograft organ transplant, or hematopoietic stem cell transplant
Significant organ impairment (renal, hepatic, cardiac, or pulmonary) or uncontrolled medical disease which, in the investigator's opinion would preclude patient participation or that may require treatment with systemic corticosteroids or immunosuppressants during the study
Active severe or unstable neuropsychiatric disease
Protocol-specified active or chronic infections, recent major episode of infection
High-risk medical conditions (e.g. high bleeding risk, history of cancer, recent major surgery, history of HLH/MAS, substance abuse within the previous year)
Other protocol-defined inclusion/exclusion criteria apply
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Reference Study ID Number: GA45767 https://forpatients.roche.com/ | Contact | 888-662-6728 (U.S.) | global-roche-genentech-trials@gene.com | |
| Fastest response: use the inquiry form. No email attachments https://www.gene.com/contact-us/submit-medical-inquiry | Contact |
| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Genentech, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham: The Kirklin Clinic | Birmingham | Alabama | 35233 | United States | ||
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| Label | URL |
|---|---|
| Please use this form to submit your questions for a faster response: https://www.gene.com/contact-us/submit-medical-inquiry. Do not include or attach any medical records when emailing or completing the form. A nurse will respond within 24 business hours. | View source |
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| Cyclophosphamide | Drug | Cyclophosphamide will be administered intravenously. |
|
| Fludarabine | Drug | Fludarabine will be administered intravenously. |
|
| Rimiducid | Drug | Rimiducid will be used as a rescue therapy in the event of the occurrence of severe or life-threatening adverse events. It will be administered intravenously. |
|
| Percentage of Participants who Achieve Sustained Drug-free Definition of Remission in SLE (DORIS) |
Drug-free DORIS is defined as a SLEDAI-2K = 0 and a PGA <0.5 (on a 3-point PGA-visual analog scale [VAS]), without corticosteroids or other immunosuppressants. |
| From Week 24 through Week 52 |
| Number of Participants With Anti-CAR T Antibodies | Up to 5 years |
| University of Iowa |
| Iowa City |
| Iowa |
| 52242 |
| United States |
| ID | Term |
|---|---|
| D008180 | Lupus Erythematosus, Systemic |
| D008181 | Lupus Nephritis |
| ID | Term |
|---|---|
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D005921 | Glomerulonephritis |
| D009393 | Nephritis |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
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| ID | Term |
|---|---|
| D003520 | Cyclophosphamide |
| C024352 | fludarabine |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
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