This is an open-label, single-arm, phase I clinical trial with dose escalation designed to investigate the safety, tolerability, and pharmacokinetic properties of Human CD19-CD22 Targeted T Cells Infusion. The primary objectives are to preliminarily assess the impact of Human CD19-CD22 Targeted T Cells Infusion in patients with relapsed/refractory B-cell acute lymphoblastic leukemia and to explore the appropriate dose and reinfusion schedule for phase II.
Eligible participants, including those with Central Nervous System Lymphoma, B Cell Lymphoma (BCL), Acute Lymphocytic Leukemia (ALL), Acute Lymphoblastic Leukemia (ALL), B Acute Lymphoblastic Leukemia (B-ALL), Refractory Non-Hodgkin Lymphoma, Refractory Chronic Lymphocytic Leukemia (CLL), Refractory B Acute Lymphoblastic Leukemia (B-ALL), Diffuse Large B Cell Lymphoma, Lymphoid Leukemia, and MRD-positive cases, can participate. Eligibility will be determined through a comprehensive assessment, including disease evaluations, a physical examination, Electrocardiograph, Computed Tomography (CT), Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), and blood tests. Prior to the infusion of CD19-CD22 CAR+ T cells, participants will undergo chemotherapy. After the infusion, participants will be closely monitored for potential side effects and the effectiveness of CD19-CD22 CAR+ T cells. Certain study procedures may be conducted during hospitalization.
Diagnosis: ALL In view of the PI and the primary oncologist, there must be no available alternative curative therapies or subject has declined to pursue alternative therapy; and subjects must be either ineligible for allogeneic stem cell transplant (SCT), have refused SCT, recurred after SCT, or have disease activity that prohibits SCT at the time of enrollment.
Chemotherapy refractory disease in subjects with B-ALL is defined as progression or stable disease after two lines of therapies
Recurrence of disease after achieving a complete response (CR).
Subjects with persistent or relapsed minimal residual disease (MRD) (by flow cytometry, PCR, FISH, or next generation sequencing) require verification of MRD positivity on two occasions at least 4 weeks apart.
Recurrent or refractory ALL limited to isolated testicular.
Subjects with radiologically-detected CNS lymphoma or CNS 3 disease (presence of ≥ 5/µL WBCs in CSF and cytospin positive for blasts [in the absence of a traumatic lumbar puncture] and/or clinical signs of CNS leukemia).
Hyperleukocytosis (≥ 50,000 blasts/µL) or rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy.
History of malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease free for at least 3 years.
Single group
CD19/CD22-CAR T cells
Biological/VaccineThe intervention in this clinical trial involves a novel approach using CD19/CD22-Chimeric Antigen Receptor T (CAR T) cells combined with chemotherapy. The goal is to assess safety and efficacy in patients with specific hematologic malignancies. Treatment Regimen: Patients in the trial will undergo the following regimen: Fludarabine Phosphate (Days -4 to -2): IV administration of fludarabine phosphate over 30 minutes on days -4 to -2. It's part of the preparatory regimen to enhance the body's response to CAR T-cell therapy. Cyclophosphamide (Day -2): IV cyclophosphamide over 60 minutes on day -2. CD19/CD22-Chimeric Antigen Receptor T Cells (Day 0): IV administration of investigational therapy, CD19/CD22-CAR T cells, over 10-20 minutes on day 0. Additional Doses: Eligible patients responding well to the initial CD19/CD22-CAR T cell infusion without unacceptable side effects and sufficient CAR T cell availability may receive 2 or 3 additional doses.
Incidence and severity of dose limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD19/CD22 chimeric antigen receptor (CAR) T cells
Will be recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 at three dose levels until the maximum tolerated dose (MTD) is determined.
Rate of successful manufacture and expansion of the CD19/CD22 chimeric antigen receptor (CAR) T cells to satisfy the targeted dose level and meet the required release specifications outlined in the Certificate of Analysis (COA)
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