A Phase 1/2 Open-Label Study to Evaluate the Safety and Efficacy of Autologous CD19-specific Chimeric Antigen Receptor T cells (CABA-201) in Subjects with Active Systemic Lupus Erythematosus
ESTADO CLÍNICO
Reclutando
FASE/S DEL ENSAYO
Fase I-II
PATOLOGÍA
Leucemia linfática crónica y otros SLPC, Leucemia linfoblástica aguda, Leucemia mieloide aguda, Terapia celular y T-CARs, Trasplante de progenitores hematopoyéticos, Linfoma
FECHA DE APERTURA
Septiembre, 2024
FECHA DE CIERRE
,
CRITERIOS DE INCLUSIÓN
Able to provide informed consent.
Diagnosed with active SLE. Subjects with either LN or without LN will be eligible, if they meet the following criteria: - For LN subjects: urine protein-to-creatinine ratio (UPCR) 1 mg/mg despite prior or current treatment with standard of care therapy
Adequate renal function
Adequate hepatic function
Have received all recommended vaccinations, including against COVID-19/severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), per the Centers for Disease Control and Prevention (CDC) or local/institutional guidelines for immunocompromised individuals before or during Screening. o Live vaccines must be administered at least 30 days prior to the Pre-Infusion Visit. o Non-live vaccines should be administered to subjects at least 2 weeks prior to the start of study drug infusion. If possible, non-live vaccines should also be administered at least 2 weeks prior to Leukapheresis.
Clinical stability by vital signs assessment at the time of screening
Women of reproductive potential (Section 9.4) who are sexually active must agree to use 1 highly effective method of contraception
Age 18 to 65 years.
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
A clinical diagnosis of SLE, based on the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for adult SLE.
Positive antinuclear antibody (ANA) titer or positive anti-dsDNA antibody at Screening.
Diagnosed with active SLE. Subjects with either LN or without LN will be eligible, if they meet the following criteria: - For LN subjects: urine protein-to-creatinine ratio (UPCR) 1 mg/mg despite prior or current treatment with standard of care therapy
Adequate renal function
Adequate hepatic function
Have received all recommended vaccinations, including against COVID-19/severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), per the Centers for Disease Control and Prevention (CDC) or local/institutional guidelines for immunocompromised individuals before or during Screening. o Live vaccines must be administered at least 30 days prior to the Pre-Infusion Visit. o Non-live vaccines should be administered to subjects at least 2 weeks prior to the start of study drug infusion. If possible, non-live vaccines should also be administered at least 2 weeks prior to Leukapheresis.
Clinical stability by vital signs assessment at the time of screening
Women of reproductive potential (Section 9.4) who are sexually active must agree to use 1 highly effective method of contraception
Age 18 to 65 years.
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
A clinical diagnosis of SLE, based on the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for adult SLE.
Positive antinuclear antibody (ANA) titer or positive anti-dsDNA antibody at Screening.
CRITERIOS DE EXCLUSIÓN
Treatment with rituximab or other B cell-depleting agent within 26 weeks prior to Screening
Previous CAR T cell therapy.
Prior solid organ (heart, liver, kidney, lung) transplant or hematopoietic cell transplant.
For LN subjects only: Evidence of severe chronicity on kidney biopsy, defined as a modified National Institute of Health chronicity index score of 3+ for any of the following individual biopsy features: total glomerulosclerosis score, fibrous crescents, tubular atrophy, or interstitial fibrosis.
Pregnant or lactating woman, or plan to become pregnant within 52 weeks following CABA-201 infusion.
Men of reproductive potential (see Section 9.4) who plan to father a child in the 52 weeks following CABA-201 infusion.
Unable or unwilling to comply with protocol.
Treatment with any investigational agent within 4 weeks or 5 half-lives, whichever is longer. Note: Subjects who had received a C5 inhibitor (e.g., eculizumab, ravulizumab) may be eligible earlier than 5 half-lives after the last C5 inhibitor administration if, at Screening, they have evidence of complement lab testing (i.e., total hemolytic complement [CH50] measurement) that has normalized or returned to pre-treatment levels.
Diagnosis of cancer, except basal or squamous cell skin cancer or carcinoma in situ of the cervix that has been excised and cured and at least 5 years since excision.
Planned major surgery (including joint surgery) within 52 weeks following the CABA-201 infusion.
Contraindication to Leukapheresis.
Active infection requiring medical intervention at Screening.
History of anaphylactic or severe systemic reaction to FLU, CY, any of their metabolites
A diagnosis of antiphospholipid antibody syndrome
Positive human immunodeficiency virus (HIV), hepatitis C antibody, or hepatitis B surface antigen test, or evidence of active or chronic tuberculosis at Screening.
Autoimmune disorder other than SLE requiring immunosuppressive therapies.
The presence of kidney disease other than active lupus nephritis
Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, psychiatric, cardiac, neurological, or cerebral disease, including severe and uncontrolled infections, such as sepsis and opportunistic infections.
Concomitant medical conditions that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study, interfere with the assessment of the effects or safety of the investigational product or with the study procedures.
The presence of severe edema or anasarca at Screening
Moderate-to-severe chronic pulmonary disease
Impaired cardiac function or clinically significant cardiac disease, including: a. Unstable angina or myocardial infarction or coronary artery bypass graft within 26 weeks prior to Leukapheresis. b. New York Heart Association stage III or IV congestive heart failure. c. History of clinically significant cardiac arrhythmia (e.g., ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular block d. History of severe non-ischemic cardiomyopathy. e. Left ventricular ejection fraction <45% as assessed by echocardiogram or multi-gated acquisition scan (if performed) 8 weeks of Leukapheresis. f. Active, severe cardiac manifestations of SLE, including constrictive pericarditis, hemodynamically significant pericardial effusions, and myocarditis at the time of screening.
Previous CAR T cell therapy.
Prior solid organ (heart, liver, kidney, lung) transplant or hematopoietic cell transplant.
For LN subjects only: Evidence of severe chronicity on kidney biopsy, defined as a modified National Institute of Health chronicity index score of 3+ for any of the following individual biopsy features: total glomerulosclerosis score, fibrous crescents, tubular atrophy, or interstitial fibrosis.
Pregnant or lactating woman, or plan to become pregnant within 52 weeks following CABA-201 infusion.
Men of reproductive potential (see Section 9.4) who plan to father a child in the 52 weeks following CABA-201 infusion.
Unable or unwilling to comply with protocol.
Treatment with any investigational agent within 4 weeks or 5 half-lives, whichever is longer. Note: Subjects who had received a C5 inhibitor (e.g., eculizumab, ravulizumab) may be eligible earlier than 5 half-lives after the last C5 inhibitor administration if, at Screening, they have evidence of complement lab testing (i.e., total hemolytic complement [CH50] measurement) that has normalized or returned to pre-treatment levels.
Diagnosis of cancer, except basal or squamous cell skin cancer or carcinoma in situ of the cervix that has been excised and cured and at least 5 years since excision.
Planned major surgery (including joint surgery) within 52 weeks following the CABA-201 infusion.
Contraindication to Leukapheresis.
Active infection requiring medical intervention at Screening.
History of anaphylactic or severe systemic reaction to FLU, CY, any of their metabolites
A diagnosis of antiphospholipid antibody syndrome
Positive human immunodeficiency virus (HIV), hepatitis C antibody, or hepatitis B surface antigen test, or evidence of active or chronic tuberculosis at Screening.
Autoimmune disorder other than SLE requiring immunosuppressive therapies.
The presence of kidney disease other than active lupus nephritis
Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, psychiatric, cardiac, neurological, or cerebral disease, including severe and uncontrolled infections, such as sepsis and opportunistic infections.
Concomitant medical conditions that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study, interfere with the assessment of the effects or safety of the investigational product or with the study procedures.
The presence of severe edema or anasarca at Screening
Moderate-to-severe chronic pulmonary disease
Impaired cardiac function or clinically significant cardiac disease, including: a. Unstable angina or myocardial infarction or coronary artery bypass graft within 26 weeks prior to Leukapheresis. b. New York Heart Association stage III or IV congestive heart failure. c. History of clinically significant cardiac arrhythmia (e.g., ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular block d. History of severe non-ischemic cardiomyopathy. e. Left ventricular ejection fraction <45% as assessed by echocardiogram or multi-gated acquisition scan (if performed) 8 weeks of Leukapheresis. f. Active, severe cardiac manifestations of SLE, including constrictive pericarditis, hemodynamically significant pericardial effusions, and myocarditis at the time of screening.
DESCRIPCIÓN
To evaluate the safety and tolerability of CABA-201 in subjects with active SLE over 28 days
PALABRAS CLAVE
acute lymphoblastic leukemia, acute myeloid leukemia, autologous, cd19, cord blood, leucemia linfocítica crónica (llc / cll), ph + acute lymphoblastic leukemia, philadelphia positive acute lymphoblastic leukemia, stem cell, umbilical cord blood
