An Exploratory Clinical Study Evaluating the Safety and Efficacy of Anti-CD19-CAR-T Cell Therapy in Subjects with Relapsed/Refractory B Cell Malignancies
Overview
- Phase
- Early Phase 1
- Intervention
- Anti-CD19-CAR-T cells
- Conditions
- B-Cell Malignancy
- Sponsor
- Shanghai First Song Biotechnology Co., LTD
- Enrollment
- 9
- Locations
- 1
- Primary Endpoint
- Manufacturing feasibility
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
This is a single-center, single-arm, open-label, exploratory study to determine the safety, tolerability, feasibility, and preliminary anti-tumor activity of anti-CD19-CAR-T cells in subjects with relapsed/refractory (r/r) B-cell malignancies.
This study plans to enroll patients with relapsed/refractory CD19-positive B-cell malignancies, who will receive a single infusion of anti-CD19-CAR-T cells after screening, PBMC collection, and lymphodepleting chemotherapy.
Detailed Description
This study will enroll subjects with CD19-positive relapsed/refractory B-cell malignancies. The effectiveness assessments for anti-CD19-CAR-T cell therapy is evaluated according to international criteria including the 2018 Lugano Classification. Toxicity is evaluated based on the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) from the National Cancer Institute. The safety of anti-CD19-CAR-T cell therapy will be evaluated through laboratory tests, 12-lead EKGs, and vital signs monitoring. Additionally, blood samples from subjects will be collected to study cellular metabolism and explore the effects of cell therapy on ferritin, C-reactive protein, and related cytokines.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects must meet all of the following criteria for inclusion in the study:
- •Patient able to provide written informed consent; parent or guardian of minor patient able to provide written informed consent; ability and willingness to adhere to the study visit schedule and all protocol requirements.
- •14 - 70 years old.
- •Relapsed/refractory disease after standard treatment (including allogeneic/autologous hematopoietic stem cell transplantation) and not eligible for other treatment options such as a second hematopoietic stem cell transplant.
- •A. Relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) is defined as one of the following:
- •Primary refractory disease.
- •Relapsed within 12 months after first remission.
- •Relapsed or refractory after two or more lines of systemic therapy.
- •Relapsed or refractory post allogeneic SCT. i. more than 100 days from the transplantation at the time of enrollment. ii. not receiving immunosuppressive drugs for 4 weeks prior to enrollment (≤5 mg prednisone or equivalent is allowed).
- •B. Ph+ B-cell ALL are eligible if they are intolerant or ineligible for tyrosine kinase inhibitor (TKI) therapy or have relapse/refractory disease after at least two different TKI treatments.
Exclusion Criteria
- •If patients meet any of the following conditions, they cannot participate in this trial:
- •Central nervous system (CNS) involvement in ALL and clinically significant neurological changes (CNS-2 and CNS-3):
- •CNS-3, defined as detectable tumor cells in cerebrospinal fluid (CSF) with ≥ 5 white blood cells (WBCs) /mm
- •CNS-2, defined as detectable tumor cells in CSF with \<5 WBCs /mm
- •Note: Subjects with CNS-1 (no detectable tumor cells in CSF) or CNS-2 without evidence of clinically significant neurological changes are eligible for this study.
- •CNS lymphoma confirmed by MRI; active CNS DLBL unless CNS involvement has been effectively treated (i.e., asymptomatic) and a local treatment interval of \> 4 weeks prior to enrollment.
- •Active CNS diseases such as epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disorders, or any autoimmune diseases involving the central nervous system.
- •Any malignancies other than CD19+ malignancies.
- •Clinically significant heart disease or arrhythmias not controlled by medication.
- •Ongoing or suspected fungal, bacterial, viral, or other infections that are uncontrolled or require intravenous antibiotic therapy; simple urinary tract infections and simple bacterial pharyngitis are allowed.
Arms & Interventions
Anti-CD19-CAR-T cell therapy
Investigational product: anti-CD19-CAR-T cells. Route of administration: Intravenous injection. Lymphodepleting chemotherapy regimen: A combination of fludarabine and cyclophosphamide will be administered prior to anti-CD19-CAR-T cells infusion.
Intervention: Anti-CD19-CAR-T cells
Anti-CD19-CAR-T cell therapy
Investigational product: anti-CD19-CAR-T cells. Route of administration: Intravenous injection. Lymphodepleting chemotherapy regimen: A combination of fludarabine and cyclophosphamide will be administered prior to anti-CD19-CAR-T cells infusion.
Intervention: Fludarabine
Anti-CD19-CAR-T cell therapy
Investigational product: anti-CD19-CAR-T cells. Route of administration: Intravenous injection. Lymphodepleting chemotherapy regimen: A combination of fludarabine and cyclophosphamide will be administered prior to anti-CD19-CAR-T cells infusion.
Intervention: Cyclophosphamide
Outcomes
Primary Outcomes
Manufacturing feasibility
Time Frame: 1 year
Percentage of subjects for whom the required dose of anti-CD19-CAR-T cells can be successfully manufactured.
Safety and tolerance
Time Frame: 28 days after anti-CD19-CAR-T cells infusion
Incidence of dose-limiting toxicity (DLT)