Status:
RECRUITING
Anti-CD19-CAR-T Cells in Subjects With Relapsed/Refractory B Cell Malignancies
Lead Sponsor:
Shanghai First Song Biotechnology Co., LTD
Collaborating Sponsors:
The First Affiliated Hospital of Anhui Medical University
Conditions:
B-Cell Malignancy
Eligibility:
All Genders
14-70 years
Phase:
EARLY_PHASE1
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 rel...
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 crite...
Eligibility Criteria
Inclusion
- 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.
- C. Relapsed/refractory B-cell non-Hodgkin lymphoma (NHL) is defined as one of the following:
- No response to first-line therapy (primary refractory disease, excluding subjects intolerant to first-line therapy):
- PD is the best response after first-line therapy.
- Best response after at least 4 cycles of first-line therapy (e.g., 4 cycles of R-CHOP) is stable disease (SD), with rapid progression in 6 months.
- No response to second or subsequent lines of therapy:
- PD is the best response to last regimen.
- Best response after at least 2 cycles of the last-line therapy is SD, with rapid progression in 6 months.
- Refractory post-autologous stem cell transplant (ASCT):
- Disease progression or relapse within 12 months (relapse must be biopsy-proven).
- If salvage therapy is given post-ASCT, the subject must have had no response to or relapsed after the last line of therapy
- Relapsed or refractory after two or more lines of systemic therapy.
- Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening
- Relapsed/refractory NHL as one of the following subtypes:
- A. DLBCL-NOS B. Primary mediastinal large B-cell lymphoma (PMBCL) C. Transformed follicular lymphoma (TFL) following prior chemotherapy for follicular lymphoma and subsequent transformation to DLBCL with refractory disease.
- D. Mantle cell lymphoma E. High-grade B-cell lymphoma F. CLL/SLL
- ECOG performance status ≤2.
- Life expectancy ≥ 12 weeks.
- Adequate venous access (for apheresis) and no other contraindications for blood cell separation.
- Subjects must meet the following laboratory criteria at screening, and they should not have received any growth factors within the 7 days prior to the hematologic assessment:
- A. Absolute neutrophil count ≥1.0×10\^9/L. For subjects with ALL, specific criteria will be determined by the investigator.
- B. Hemoglobin ≥60 g/L (without RBC transfusion within 14 days). C. Platelets ≥50×10\^9/L. For subjects with ALL, specific criteria will be determined by the investigator.
- D. Absolute lymphocyte count (ALC) ≥0.5×10\^9/L. If the total lymphocyte count is insufficient with a high proportion of T cells, the investigator may discuss with the sponsor.
- E. Total bilirubin \<1.5×ULN; if liver involved, total bilirubin \<3.0×ULN is allowed.
- F. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN; if liver involved, ALT/AST ≤5×ULN is allowed.
- G. Creatinine \<1.5×ULN and estimated creatinine clearance ≥60 mL/min.
- Cardiac ejection fraction (EF) ≥45% with no clinically significant findings on electrocardiogram.
- Baseline oxygen saturation \>92% on room air.
- Women of childbearing potential must have a negative serum or urine pregnancy test (women who have undergone surgical sterilization or have been postmenopausal for at least 2 years are not considered of childbearing potential).
Exclusion
- 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) /mm3.
- CNS-2, defined as detectable tumor cells in CSF with \<5 WBCs /mm3. 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.
- Hepatitis B (positive for hepatitis B surface antigen and hepatitis B DNA \>1000 copies/mL) and hepatitis C (positive for hepatitis C antibodies); syphilis, human immunodeficiency virus (HIV) infection.
- Presence of any indwelling or drainage catheter (e.g., percutaneous nephrostomy, indwelling Foley catheter, biliary drainage catheter, pleural/peritoneal/pericardial drainage catheter); the use of dedicated central venous access devices such as Port-A-Cath® or Hickman® catheters is allowed.
- Prior use of the following:
- CD19-targeted therapy.
- Chlorambucil or bendamustine within 3 months before enrollment, or PEG-asparaginase within 3 weeks before enrollment.
- live vaccines within 4 weeks before enrollment.
- Donor lymphocyte infusions (DLI) within 4 weeks before enrollment.
- Medications for graft-versus-host disease (GVHD) treatment within 4 weeks before enrollment, such as calcineurin inhibitors, methotrexate, mycophenolate, rapamycin, or siltuximab, or use of immunosuppressive antibodies (anti-CD20, anti-tumor necrosis factor, anti-interleukin 6, or anti-interleukin 6 receptor) within 4 weeks before enrollment.
- Immunostimulatory or immunosuppressive therapy within 4 weeks before enrollment, including interferon-α, interferon-β, IL-2, lenalidomide, efalizumab, alemtuzumab, tocilizumab, cyclosporine, or thalidomide.
- Anti-PD-1/anti-PD-L1 therapy within 4 weeks before enrollment.
- Systemic cytotoxic chemotherapy within 14 days before enrollment, including daily or weekly low-dose maintenance chemotherapy (e.g., cyclophosphamide, ifosfamide, bendamustine, chlorambucil, melphalan, or vincristine).
- Long-acting growth factors (e.g., pegfilgrastim) within 14 days before apheresis or short-acting growth factors within 5 days before apheresis or mobilization agents (e.g., filgrastim/pegfilgrastim, plerixafor) within 5 days before apheresis.
- Radiation therapy within 14 days before enrollment.
- Pharmacological doses of corticosteroids (\>5 mg/day prednisone or equivalent) or other immunosuppressive drugs within 7 days before enrollment.
- Venetoclax (BCL-2 inhibitor) within 4 days before apheresis.
- Short-acting targeted therapy (e.g., tyrosine kinase inhibitors) within 72 hours before apheresis.
- Idelalisib (oral PI3Kδ inhibitor) within 2 days before apheresis.
- Lenalidomide within 1 day before enrollment.
- ≥ Grade 2 graft-versus-host disease (GVHD) per the CIBMTR grading system or requiring systemic corticosteroid treatment exceeding physiological doses.
- A history of autoimmune diseases in the past 2 years, such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, leading to end-organ damage or requiring systemic immunosuppression or disease-modifying agents.
- A history of heart attack, cardiac catheterization or stent implantation, unstable angina, or other clinically significant heart diseases within 12 months before enrollment.
- A history of genetic syndrome with bone marrow failure, such as Fanconi anemia, Kostmann syndrome, Schwachman-Diamond syndrome, etc.
- Symptomatic deep vein thrombosis or pulmonary embolism requiring systemic anticoagulation within 6 months before enrollment. Subjects need to be on prophylactic anticoagulation.
- A history of or currently having other malignant tumors (excluding skin basal cell carcinoma, breast/cervical carcinoma in situ, and other malignant tumors that have not been treated in the past five years but are effectively controlled).
- Use of other investigational medicinal products within 30 days before screening.
- Pregnant, planning to become pregnant, or breastfeeding in reproductive-aged women. Women who have undergone surgical sterilization or have been postmenopausal for at least 2 years are not considered to be of reproductive potential.
- Male and female subjects unwilling to practice contraception from the time of agreeing to treatment until 12 months after completion of conditioning chemotherapy or CAR-T infusion.
- Any past medical history that may interfere with the safety of the study treatment or the evaluation of efficacy.
- Based on the investigator's judgment, subjects are unlikely to complete all the study visits or procedures required by the protocol.
- Previous use of any CAR-T cell product or other gene-modified T cell therapy.
Key Trial Info
Start Date :
August 24 2023
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
September 1 2026
Estimated Enrollment :
9 Patients enrolled
Trial Details
Trial ID
NCT06532630
Start Date
August 24 2023
End Date
September 1 2026
Last Update
February 28 2025
Active Locations (1)
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1
The First Affiliated Hospital of Anhui Medical University
Hefei, Anhui, China, 230022