Anti-CD19-CAR-T Cells in Relapsed/Refractory B-cell Tumor Patients.

NCT06375161 | Recruiting Early Phase 1 DMC

• 1 other identifier: CD19-CN-A6
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-center, open-label, single-dose clinical trial of anti-CD19-CAR-T cell therapy in relapsed/refractory B-cell tumor patients after Qinglin pre-treatment. In this study phase, a traditional "3+3" trial design is employed for dose escalation.

Conditions

B Cell Malignancies

Outcome Measures

Primary Outcomes (1)

• Incidence of dose-limiting toxicity

  The proportion of patients receiving CAR-T cells who encounter dose-limiting toxicities (DLTs). Safety evaluations are performed in accordance with the NCI-CTCAE version 5.0 standards (Cytokine Release Syndrome and neurotoxicity will be graded based on ASTCT/ASBMT grading criteria).

  Up to 28 days from CAR-T infusion

Study Arms (1)

anti-CD19-CAR-T Cells

EXPERIMENTAL

anti-CD19-CAR-T cell infusion. Infusion doses: The planned infusion doses are as follows: the first dose group at 1×10\^5 cells/kg; the second dose group at 3×10\^5 cells/kg; the third dose group at 1×10\^6 cells/kg. Infusion doses refer to the number of CAR-positive cells. Administration route: anti-CD19-CAR-T cells are administered via intravenous drip at a rate of approximately 2 to 5 mL/minute using an infusion pump, with a recommended infusion time of less than 30 minutes.

Biological: anti-CD19-CAR-T cells

Interventions

anti-CD19-CAR-T cells BIOLOGICAL

Before cell infusion, Investigator may decide, based on necessity, whether to administer prophylactic medication, which may include options such as acetaminophen and diphenhydramine, or H1 antihistamines, among others. Subjects are allowed to receive adequate supportive care after anti-CD19-CAR-T cell infusion, including blood transfusions and blood products, antibiotic therapy, antiemetics, antidiarrheals, analgesics, etc.

anti-CD19-CAR-T Cells

Eligibility Criteria

• Age: 18 Weeks - 70 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Voluntary participation in the clinical trial; the individual or legal guardian fully understands and consents to the study by signing the Informed Consent Form (ICF); willing and able to comply with all trial procedures.
• Age between 18-70 years.
• Patients who are refractory or relapsed after current standard treatments (including allogeneic or autologous hematopoietic stem cell transplantation), and not suitable for other treatment options such as a second hematopoietic stem cell transplantation.
• Relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) is defined as one of the following:
• \- Primary refractory disease
• \- First relapse if the first remission was ≤12 months
• Relapse or refractory disease after two or more lines of systemic therapy
• Relapse or refractory disease after allogeneic transplantation, provided that at least 100 days have elapsed since transplantation at the time of enrollment, and no immunosuppressive drugs have been used for at least 4 weeks prior to enrollment, except for low-dose steroids (≤5 mg prednisone or equivalent).
• Subjects with Ph+ B-cell ALL who are intolerant or ineligible for treatment with tyrosine kinase inhibitors (TKIs), or have relapsed/refractory disease after receiving at least two different TKI treatments, are eligible.
• Relapsed/refractory B-cell non-Hodgkin lymphoma (NHL) is defined as one of the following:
• No response to first-line treatment (primary refractory disease); excluding subjects intolerant to first-line chemotherapy - PD as the best response to first-line treatment - Best response after at least 4 cycles of first-line treatment (such as 4 cycles of RCHOP) is SD, and the duration of SD after the last dose does not exceed 6 months.
• No response to second-line or subsequent treatments - PD as the best response to the most recent treatment regimen - Best response after at least 2 cycles of last-line treatment is SD, and the duration of SD after the last dose does not exceed 6 months.
• Refractory after ASCT
• \- Disease progression or relapse ≤12 months post-ASCT (relapse must be confirmed by biopsy).
• If salvage therapy is given post-ASCT, subjects must have had no response or relapse after the last-line treatment.

You may not qualify if:

• (1) ALL with central nervous system abnormalities, excluding clinically evident neurological changes CNS-2 and CNS-3.
• \) CNS-3 disease, defined as detectable tumor cells in the cerebrospinal fluid (CSF), with ≥5 WBCs per mm3, with or without neurological changes.
• \) CNS-2 disease, defined as detectable tumor cells in the CSF, with \<5 WBCs per mm3, and neurological changes.
• Note: Subjects with CNS-1 (no tumor cells detected in CSF) and CNS-2 with no clinically evident neurological changes are eligible for this study.
• (2) Evidence of central nervous system lymphoma on brain MRI; active primary central nervous system DLBCL, unless the central nervous system involvement has been effectively treated (i.e., participants are asymptomatic), and \>4 weeks have elapsed since local treatment before enrollment.
• (3) Active central nervous system diseases such as epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar diseases, or any autoimmune diseases involving the central nervous system.
• (4) History of or concurrent malignancies other than CD19+ malignancies.
• (5) Clinically significant cardiac diseases, or arrhythmias not controlled by medication.
• (6) Presence or suspicion of uncontrolled fungal, bacterial, viral, or other infections, or requiring intravenous antibiotic therapy; simple urinary tract infections and uncomplicated bacterial pharyngitis are allowed if responsive to treatment and after consultation with the sponsor's medical monitor.
• (7) Hepatitis B (positive for hepatitis B surface antigen and/or positive for hepatitis B core antibody with hepatitis B DNA \>1000 copies/ml) and hepatitis C (positive for hepatitis C antibody); syphilis, human immunodeficiency virus (HIV) infection.
• (8) Presence of any indwelling catheter or drainage tube (such as percutaneous nephrostomy tube, indwelling Foley catheter, bile drainage tube, or pleural/peritoneal/pericardial catheter); use of dedicated central venous access devices such as Port-A-Cath® or Hickman® catheters is allowed.
• (9) Prior medication:
• CD19-targeted therapy.
• Use of chlorambucil or cladribine within 3 months prior to enrollment, or use of PEG-asparaginase within 3 weeks prior to enrollment.
• Injection of live vaccines within 4 weeks prior to enrollment.

Sponsors & Collaborators

• Shanghai Tongji Hospital, Tongji University School of Medicine: lead

Study Sites (1)

Shanghai Tongji Hospital

Shanghai, Shanghai Municipality, 200333, China

RECRUITING

Study Officials

• Aibin Liang

  Shanghai Tongji Hospital, Tongji University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aibin Liang

CONTACT

+86 21 6611 1019; lab7182@tongji.edu.cn

Ping LI

CONTACT

+86 135 6418 1131; lilyforever@126.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor,Chief Physician,Vice President of Tongji Hospital, Tongji University School of Medicine etc.

Study Record Dates

• First Submitted: April 16, 2024
• First Posted: April 19, 2024
• Study Start: December 11, 2023
• Primary Completion: December 10, 2025
• Study Completion (Estimated): December 10, 2039
• Last Updated: April 19, 2024

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)