Clinical trial NCT05932173: A Study of Novel Anti-CD19 CAR-T in Patients With r/r B-Cell Malignancies
Official title: An Open Label, Single-site, Dose-escalation Study Aiming to Evaluate the Efficacy and Safety of Anti-CD19 CAR-T Manufactured by OlyCAR Platform(OlyCAR-019) in the Treatment of Relapsed/ Refractory(r/r) B-Cell Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: B-Cell Leukemia
B-Cell Lymphoma
B-cell Tumors
Keywords: B Cell
CAR-T
CD19
Leukemia
Lymphoma
Lead sponsor: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
Sponsor class: OTHER
First posted: 2023-07-06
Enrollment: 60
Sex: ALL
Minimum age (years): 2
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Patients will receive one of the three doses of 0.5-2\*10\^6/kg, 3-4\*10\^6/kg, 5-6\*10\^6/kg.
Primary purpose: TREATMENT

Brief summary: It is a single-center, open-labeled, single-arm, non-randomized, investigator-initiated trial aiming to evaluate the efficacy and safety of anti-CD19 CAR-T manufactured by OlyCAR platform (OlyCAR-019) for CD19+ refractory/relapsed B-Cell malignancies.

Detailed description: OlyCAR is a novel CAR-T manufacturing system which allows to generate clinical-use CAR-T cells in short time. This study is going to evaluate the feasibility of CAR-T manufactured by OlyCAR platform in the treatment of B-Cell malignancies. The OlyCAR-019 cells will be infused by vein. Subjects will be followed for safety and efficacy up to 12 weeks. For those with a durable remission 12 weeks after infusion, the follow-up will last for at least 12 months for disease control.

Eligibility criteria: Key Inclusion Criteria:

1. A definite diagnosis of relapsed/refractory B-cell malignancies;
2. Male or female, aged 2-75 years;
3. Confirmed detectable disease；
4. Expected survival time \>12 weeks;
5. Eastern cooperative oncology group (ECOG) score is 0-2;
6. Adequate liver , kidney and cardiopulmonary function;
7. Women of childbearing age have negative blood pregnancy test before the start of the trial, and agree to take effective contraceptive measures during the trial until the last follow-up; male subjects with partners of childbearing potential agree to take effective contraceptive measures during the trial until the last follow-up;
8. Willingness to complete the informed consent process and to comply with study procedures and visit schedule.

Key Exclusion Criteria:

1. Presence of other concurrent active malignancy; People with severe mental disorders;
2. History of any of the following genetic disorders, such as Fanconi anemia, Schu-Day syndrome, Gerstmann syndrome, or any other known bone marrow failure syndrome;
3. Acute GVHD of grade II-IV or extensive chronic GVHD;
4. Grade III-IV heart failure or myocardial infarction, cardiac angioplasty or stenting, unstable angina pectoris, or other clinically prominent heart disease within one year prior to enrollment;
5. The presence of any indwelling catheter or drainage (e.g., percutaneous nephrostomy, indwelling catheter, bile drainage, or pleural/peritoneal/pericardial catheter), except for patients who are permitted to use dedicated central venous catheters;
6. Human immunodeficiency virus (HIV) seropositivity; Hepatitis B surface antigen positive or hepatitis B core antibody positive, and HBV-DNA positive; Patients with hepatitis C (HCV-RNA quantitative test results positive); Or the presence of other serious active viral or bacterial infections or uncontrolled systemic fungal infections; Patients with severe history of allergy or allergic constitution;
7. A history of autoimmune diseases (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) leading to end-organ damage or requiring systemic immunosuppressive/systemic disease modulating drugs within the past 2 years; Had or is suffering from interstitial lung disease (e.g., pneumonia, pulmonary fibrosis);
8. Had undergone other clinical trials in the 4 weeks prior to participating in this trial;
9. Poor compliance due to physiological, family, social, geographical and other factors, unable to cooperate with the study protocol and follow-up plan;
10. For patients contraindicated with cyclophosphamide and fludarabine chemotherapy;
11. Subjects requiring systemic corticosteroid therapy (prednisone ≥5mg/ day or equivalent dose of another corticosteroid) or other immunosuppressive agents within 1 month after UCAR-T cell reinfusion, except for adverse events;
12. Receiving donor lymphocyte infusion within 6 weeks before enrollment;
13. Pregnant and lactating women;
14. Subjects with any other condition which the investigator considers unsuitable for inclusion in the study.

Primary outcomes:
measure: Incidence of adverse events(AE) after infusion
timeFrame: Up to 12 months after infusion
measure: MTD
timeFrame: Up to 28 days after infusion
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 3 months after infusion
measure: Progression-free survival(PFS)
timeFrame: Up to 3 months after infusion
Other outcomes:
Locations:
city: Kunming
country: China
facility: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
state: Yunnan
Study officials:
affiliation: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
name: Sanbin Wang, Professor
role: PRINCIPAL_INVESTIGATOR
References: