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

Recruiting now · Early Phase 1

Conditions studied: B Cell Malignancies

In brief

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.

Key facts

Study ID

NCT06375161

Run by

Shanghai Tongji Hospital, Tongji University School of Medicine

People needed

12

Starts

2023-12-11

Expected to finish

2039-12-10

Last updated by the study team

2024-04-19

Who can join

Age: 0 and older, up to 1. Sex: any. Healthy volunteers: not accepted.

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.
• Bone marrow smear reports showing tumor cells ≥5% in ALL patients.
• Patients with refractory or relapsed NHL meet one of the following subtypes:
• DLBCL-NOS. 2) Primary mediastinal large B-cell lymphoma (PMBCL). 3) Transformed follicular lymphoma (TFL), previously treated with follicular lymphoma chemotherapy, subsequently transformed into refractory disease after DLBCL.
• Mantle cell lymphoma. 5) High-grade B-cell lymphoma. 6) CLL/SLL.
• (6) ECOG performance status ≤2.
• (7) Estimated life expectancy of at least 12 weeks.
• (8) Adequate venous access (for single collection) and no other contraindications to blood cell separation.
• (9) Laboratory test results at screening must meet the following requirements, and subjects must not have received colony-stimulating factors (G-CSF/PEG-CSF) within 2 weeks prior to hematological assessment (except for low-dose steroids):
• Absolute neutrophil count ≥1.0×10\^9/L, ALL eligibility to be determined by the investigator.
• Hemoglobin ≥60 g/L (without red blood cell transfusion within 14 days). 3) Platelets ≥50×10\^9/L, ALL eligibility to be determined by the investigator. 4) Absolute lymphocyte count (ALC) ≥ 0.5×10\^9/L; if insufficient, and T-cell proportion is high in the lymphocyte subset, the investigator can discuss with the sponsor.

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.
• Donor lymphocyte infusion (DLI) within 28 days prior to enrollment.
• Any drugs used for GVHD treatment within 4 weeks prior to enrollment (such as calcineurin inhibitors, methotrexate, mycophenolate, rapamycin, or salidroside), or use of immunosuppressive antibodies (such as anti-CD20, anti-tumor necrosis factor, anti-interleukin-6, or anti-interleukin-6 receptor) within 4 weeks prior to enrollment.
• Immunostimulatory or immunosuppressive therapy within 4 weeks prior to enrollment (such as interferon-alpha, interferon-beta, IL-2, enoxaparin, efalizumab, alemtuzumab, tacrolimus, or mycophenolate).
• Any systemic inhibitory/stimulatory immune checkpoint molecule therapy within 4 weeks prior to enrollment (e.g., ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists, etc.).
• Use of systemic cytotoxic drugs within 2 weeks prior to enrollment, including daily or weekly low-dose maintenance chemotherapy (such as cyclophosphamide, ifosfamide, bendamustine, chlorambucil, or mephalan, vincristine, etc.).
• Long-acting growth factors within 14 days prior to single collection (such as pegfilgrastim) or short-acting growth factors within 5 days prior to single collection or drugs used for cell mobilization (such as G-CSF/PEG-CSF, plerixafor).
• Receipt of radiotherapy within 2 weeks prior to enrollment.
• Must avoid pharmacological doses of corticosteroids (>5 mg/day of prednisone or equivalent) and other immunosuppressive drugs within 7 days prior to single collection.
• Use of venetoclax (BCL-2 inhibitor) within 4 days prior to single collection.
• Short-acting targeted therapies (such as tyrosine kinase inhibitors) within 72 hours prior to single collection.

Where it is running

• Shanghai Tongji Hospital — Shanghai, Shanghai Municipality, China (enrolling)

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.