TCR Reserved and Power3 (SPPL3) Gene Knock-out Allogeneic CD19-targeting CAR-T Cell Therapy in r/r B-ALL

Launched by CHINESE PLA GENERAL HOSPITAL · Jun 27, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new type of treatment for patients with a specific kind of blood cancer called relapsed or refractory B-cell Acute Lymphoblastic Leukemia (B-ALL). The treatment involves using modified immune cells, known as CAR-T cells, which are designed to target and destroy cancer cells. In this study, researchers are focusing on a special version of these CAR-T cells that have had specific genes disabled to improve their effectiveness and reduce the risk of side effects, such as a condition called Graft-versus-Host Disease (GvHD).

To participate in this trial, patients need to be between 16 and 70 years old and have been diagnosed with this type of leukemia that has either returned after treatment or did not respond to previous therapies. Other key requirements include a stable recovery from any prior treatment side effects and good overall health, including proper kidney and liver function. Participants can expect to receive this innovative therapy and will be closely monitored by doctors throughout the process to ensure their safety and assess how well the treatment is working. This trial is currently recruiting participants, and those interested should discuss it with their healthcare provider.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Age 16-70 (inclusive).
• • 2. Patient with r/r CD19+ B-ALL, as per guidelines (NCCN, 2019)
• • morphologically confirmed with ≥ 5% leukaemic blasts in the bonemarrow;
• • or presenting a quantifiable MRD load of 1x10\^-3 , assessed by multiparameter flow cytometry and/or quantitative polymerase chain reaction, at the end of the last induction treatment.
• Relapsed disease is defined as:
• • second or subsequent bone marrow relapse or,
• • any bone marrow relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
• • Refractory disease is defined by not achieving an initial CR after 2 cycles of a standard chemotherapy regimen (primary refractory). Subjects who were refractory to subsequent chemotherapy regimens after an initial remission were considered chemorefractory.
• • 3. Those who relapsed 3 months post allo-HSCT or autologous CAR-T therapy can be enrolled.
• • 4. Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for hematological toxicities and clinically non-significant toxicities such as alopecia).
• • 5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• 6. Adequate renal, hepatic, pulmonary and cardiac function defined as:
• • Serum creatinine≤1.5 upper limit of normal (ULN) or creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min.
• • Serum alanine aminotransferase / aspartate aminotransferase (ALT/AST) ≤ 3 upper limit of normal (ULN); Total bilirubin ≤ 1.5 ULN, except in subjects with 3) Gilbert's syndrome.
• • Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings.
• • Coagulation Function: International Normalized Ratio (INR) ≤ 1.5 times the upper limit of normal (ULN), and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 times ULN.
• • Baseline oxygen saturation \>91% on room air.
• • 7. Subjects of both genders who are willing to practice birth control from the time of consent through 6 months after the completion of conditioning chemotherapy. Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential).
• • 8. Voluntarily participate in this clinical trial and sign an informed consent form.
• Exclusion Criteria:
• • 1. Expected survival time \< 3 months per Principal Investigator's opinion.
• • 2. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease free for at least 3 years.
• • 3. Patients who received any immunocellular therapy within 3 months before enrollment.
• • 4. Active central nervous system (CNS) leukaemia (CNS-3).
• • 5. Clinically active significant CNS dysfunction.
• • 6. Known history of irreversible severe neurological toxicity related to previous antileukaemic treatment leading to organic central nervous system lesions.
• • 7. Use of previous anti-leukemic therapy within 5 half-lives prior to allogeneic Power3 (SPPL3) knock-out CD19 CAR-T administration; participation in non-interventional registries or epidemiological studies is allowed.
• • 8. Radioimmunotherapy, radiotherapy, within 8 weeks (except prophylaxis of CNS involvement) before Inclusion.
• • 9. History of severe, immediate hypersensitivity reaction attributed to lymphodepletion drugs or any component of allogeneic Power3 (SPPL3) knock-out CD19 CAR-T.
• • 10. Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management.
• • 11. Uncontrolled or active infectious diseases, such as human immunodeficiency virus (HIV) infection, acute or chronic active hepatitis B or C, epstein-barr virus (EBV), and cytomegalovirus (CMV) infection.
• • 12. History or presence of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
• • 13. Subjects with cardiac atrial or cardiac ventricular lymphoma involvement.
• • 14. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment.
• • 15. Expected or possible requirement for urgent therapy within 6 weeks due to ongoing or impending oncologic emergency (eg, tumor mass effect, tumor lysis syndrome).
• • 16. Primary immunodeficiency.
• • 17. History of autoimmune disease (e.g. Crohn's, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years.
• • 18. History of symptomatic deep vein thrombosis or pulmonary embolism requiring systemic anticoagulation within 6 months of enrollment.
• • 19. Any medical condition likely to interfere with assessment of safety or efficacy of study treatment.
• • 20. History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• • 21. Vaccine ≤ 6 weeks prior to planned start of conditioning regimen.
• • 22. In the investigator's judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.