RECRUITING

CD19-Directed Chimeric Antigen Receptor Autologous T Cells (CART19) for Lupus

Conditions

SLE Systemic Lupus Erythematosus (SLE)CAR T Cell CART19 Cell Therapy Lupus Lupus Nephritis (LN)

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a single-center, single-arm, open-label phase 1/2 study of CART19 in children and young adults with refractory Systemic lupus erythematosus (SLE), including both patients diagnosed with lupus nephritis (LN) and patients with non-renal Systemic lupus erythematosus (SLE). Phase 1 will evaluate the safety of CART19 in 6-12 patients with Systemic lupus erythematosus (SLE). There is no planned dose escalation, but a dose de-escalation will be made based on the incidence of Dose Limiting Toxicities. Phase 2 will evaluate the efficacy and further evaluate the safety of CART19 in this population.

Official Title

CD19-Directed Chimeric Antigen Receptor Autologous T Cells (CART19) for Adolescents and Young Adults With Systemic Lupus Erythematosus (SLE)

Quick Facts

Study Start:2025-03-31

Study Completion:2030-02-28

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06839976

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:12 Years to 29 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
1. Signed informed consent form must be obtained prior to any study procedure. Labs or other procedures obtained during routine clinical care may be used for eligibility if obtained within the protocol required window. 2. Patient age must be 12-29 years, inclusive, at time of enrollment. 3. Meeting ACR/EULAR Classification Criteria for SLE 4. ANA positive \> 1:80 and/or double-stranded DNA (dsDNA) positive 5. Active (refractory) disease, despite at least three months of conventional therapy, defined as follows: 1. \> 1000mg/g creatinine 2. \> 500 mg/g creatinine associated with renal dysfunction or low albumin. 3. \> 500 mg/g creatinine in a patient with rising proteinuria after prior complete renal response b. Non-renal SLE subjects must meet either of the following criteria: i. SLEDAI-2K ≥ 8 and clinical SLEDAI-2K ≥ 6 ii. Inability to decrease prednisone ≤7.5mg/day or 0.15mg/kg/day, whichever is lower, due to active disease. 6. Patients must have had at least 3 months conventional therapy defined as: 1. Conventional induction immunosuppressive agent(s) (mycophenolate mofetil or cyclophosphamide), and 2. At least one additional therapy: 1. Renal: eGFR must be ≥30 and subject cannot be receiving dialysis. 2. Hepatic: Transaminases \< 5x upper limit of normal and serum conjugated (Direct) bilirubin \<1.5x upper limit of normal unless attributable to SLE. If attributable to autoimmune disease, Child-Pugh score must be class A or class B. Child-Pugh score cannot be class C. 3. Cardiac: Shortening fraction \> 28%, left ventricular ejection fraction \>45%, and no evidence of severe pulmonary hypertension 4. Pulmonary: Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and \<Grade 3 hypoxia; DLCO ≥40% (corrected for anemia and/or VA volume) if PFTs are clinically appropriate as determined by the treating investigator. 8. Subjects of reproductive potential must agree to use acceptable birth control methods.	1. Active, untreated infections 2. HIV infection 3. Active Hepatitis B 4. Hepatitis C 5. Patients with severe neuropsychiatric lupus or neurologic manifestations of SLE (e.g. stroke, seizure, psychosis, demyelinating syndromes, organic brain syndrome, or lupus related headaches) 6. Monogenic lupus (known) 7. Previous autologous or allogenic stem cell transplant 8. Previous kidney transplant 9. History of seizure disorder 'Patients who are on anti-epileptic therapy. 10. Participation in a clinical trial in which the patient receives an investigational drug within a time period equal or less than 5.5 half-lives of the investigational agent prior to study enrollment. 11. Use of concurrent immunosuppression 1. Given the potential risks of additive immunosuppression and potentially deleterious effects of steroids, DMARDs and other biologics on the CART product, these medications are standardly discontinued prior to any cellular therapy. Subjects should be on stable doses of DMARDs for at least two weeks prior to enrollment. Subjects who are unwilling or unable to discontinue disallowed immunosuppressive medications at the times of T cell collection and CART19 infusion will be excluded from the trial. 2. Disallowed immunosuppression includes any therapy (drugs, biologics or other treatments) clearly given for the purpose of treating the underlying autoimmune disease. This will include any FDA-approved or experimental agents not currently available but that become available during the period of the trial. Anti-malarial drugs for the treatment of SLE are permitted. The use of physiologic replacement hydrocortisone (or equivalent) or inhaled steroids is permitted. 3. Immunosuppression for SLE treatment at times other than cell collection or at the time of infusion are permitted. 12. Any comorbidity that in the opinion of the investigators would jeopardize the ability of the subject to tolerate therapy. 13. Pregnant patients. All participants of childbearing potential must have negative pregnancy test. 14. Lactating participants who want to continue breastfeeding. 15. Patients who are unwilling to consent to LTFU

Inclusion Criteria

Exclusion Criteria

1. Signed informed consent form must be obtained prior to any study procedure. Labs or other procedures obtained during routine clinical care may be used for eligibility if obtained within the protocol required window.
2. Patient age must be 12-29 years, inclusive, at time of enrollment.
3. Meeting ACR/EULAR Classification Criteria for SLE
4. ANA positive \> 1:80 and/or double-stranded DNA (dsDNA) positive
5. Active (refractory) disease, despite at least three months of conventional therapy, defined as follows:
1. \> 1000mg/g creatinine
2. \> 500 mg/g creatinine associated with renal dysfunction or low albumin.
3. \> 500 mg/g creatinine in a patient with rising proteinuria after prior complete renal response b. Non-renal SLE subjects must meet either of the following criteria: i. SLEDAI-2K ≥ 8 and clinical SLEDAI-2K ≥ 6 ii. Inability to decrease prednisone ≤7.5mg/day or 0.15mg/kg/day, whichever is lower, due to active disease.
6. Patients must have had at least 3 months conventional therapy defined as:
1. Conventional induction immunosuppressive agent(s) (mycophenolate mofetil or cyclophosphamide), and
2. At least one additional therapy:
1. Renal: eGFR must be ≥30 and subject cannot be receiving dialysis.
2. Hepatic: Transaminases \< 5x upper limit of normal and serum conjugated (Direct) bilirubin \<1.5x upper limit of normal unless attributable to SLE. If attributable to autoimmune disease, Child-Pugh score must be class A or class B. Child-Pugh score cannot be class C.
3. Cardiac: Shortening fraction \> 28%, left ventricular ejection fraction \>45%, and no evidence of severe pulmonary hypertension
4. Pulmonary: Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and \<Grade 3 hypoxia; DLCO ≥40% (corrected for anemia and/or VA volume) if PFTs are clinically appropriate as determined by the treating investigator.
8. Subjects of reproductive potential must agree to use acceptable birth control methods.

1. Active, untreated infections
2. HIV infection
3. Active Hepatitis B
4. Hepatitis C
5. Patients with severe neuropsychiatric lupus or neurologic manifestations of SLE (e.g. stroke, seizure, psychosis, demyelinating syndromes, organic brain syndrome, or lupus related headaches)
6. Monogenic lupus (known)
7. Previous autologous or allogenic stem cell transplant
8. Previous kidney transplant
9. History of seizure disorder 'Patients who are on anti-epileptic therapy.
10. Participation in a clinical trial in which the patient receives an investigational drug within a time period equal or less than 5.5 half-lives of the investigational agent prior to study enrollment.
11. Use of concurrent immunosuppression
1. Given the potential risks of additive immunosuppression and potentially deleterious effects of steroids, DMARDs and other biologics on the CART product, these medications are standardly discontinued prior to any cellular therapy. Subjects should be on stable doses of DMARDs for at least two weeks prior to enrollment. Subjects who are unwilling or unable to discontinue disallowed immunosuppressive medications at the times of T cell collection and CART19 infusion will be excluded from the trial.
2. Disallowed immunosuppression includes any therapy (drugs, biologics or other treatments) clearly given for the purpose of treating the underlying autoimmune disease. This will include any FDA-approved or experimental agents not currently available but that become available during the period of the trial. Anti-malarial drugs for the treatment of SLE are permitted. The use of physiologic replacement hydrocortisone (or equivalent) or inhaled steroids is permitted.
3. Immunosuppression for SLE treatment at times other than cell collection or at the time of infusion are permitted.
12. Any comorbidity that in the opinion of the investigators would jeopardize the ability of the subject to tolerate therapy.
13. Pregnant patients. All participants of childbearing potential must have negative pregnancy test.
14. Lactating participants who want to continue breastfeeding.
15. Patients who are unwilling to consent to LTFU

Contacts and Locations

Study Contact

Caitlin Elgarten, MD

CONTACT

267-425-7964

elgartenc@chop.edu

Melissa Varghese

CONTACT

845-553-5358

verghesem@chop.edu

Principal Investigator

Caitlin Elgarten, MD

PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Study Locations (Sites)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104

United States

Collaborators and Investigators

Sponsor: Children's Hospital of Philadelphia

Caitlin Elgarten, MD, PRINCIPAL_INVESTIGATOR, Children's Hospital of Philadelphia

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-03-31

Study Completion Date2030-02-28

Study Record Updates

Study Start Date2025-03-31

Study Completion Date2030-02-28

Terms related to this study

Additional Relevant MeSH Terms

SLE
Systemic Lupus Erythematosus (SLE)
CAR T Cell
CART19
Cell Therapy
Lupus
Lupus Nephritis (LN)