Status:
NOT_YET_RECRUITING
An Exploratory Clinical Study Evaluating the Safety and Efficacy of Intravenous Anti-CD20/CD30-CAR-T Cell Infusion in Relapsed/Refractory Lymphoma Patients.
Lead Sponsor:
Shanghai Tongji Hospital, Tongji University School of Medicine
Conditions:
B Cell Malignancies
Eligibility:
All Genders
18-70 years
Phase:
EARLY_PHASE1
Brief Summary
This study is a single-center,open-label,single-dose clinical trial of anti-CD20/CD30-CAR-T cell therapy in relapsed/refractory B-cell tumor patients after lymphocyte depletion pre-treatment. In this...
Detailed Description
This study is a single-center, open-label, single-dose clinical trial of anti-CD20/CD30-CAR-T cell therapy in relapsed/refractory lymphoma patients after lymphocyte depletion pre-treatment. The study...
Eligibility Criteria
Inclusion
- (1) Voluntary participation in the clinical study; complete understanding by self or legally authorized guardian, informed of the study, and signing the Informed Consent Form (ICF); willing and able to comply with all trial procedures.
- (2) Age between 18 and 70 years.
- (3) Patients refractory or relapsed after current standard treatments (including allogeneic or autologous hematopoietic stem cell transplantation), and unsuitable for other treatment options such as second hematopoietic stem cell transplantation. Refractory/relapsed lymphoma is defined as:
- No response to first-line therapy (primary refractory disease, excluding subjects intolerant to first-line therapy):
- \- Progression of Disease (PD) assessment after first-line treatment
- Best response of Stable Disease (SD) after at least 4 cycles of first-line treatment (e.g., 4 cycles of RCHOP), with SD maintenance duration not exceeding 6 months after the last dose.
- No response to second-line or subsequent therapies:
- PD as best response to the most recent treatment regimen
- Best response of SD after at least 2 cycles of last-line treatment, with SD maintenance duration not exceeding 6 months after the last dose.
- Refractory post autologous stem cell transplantation (ASCT):
- Disease progression or relapse ≤12 months after ASCT (relapsing subjects must have biopsy-proven relapse)
- If salvage therapy is performed post-ASCT, subjects must have had no response or relapse after the last-line treatment.
- Relapsed or refractory disease after two or more lines of systemic therapy.
- (4) Lymphoma patients with target antigens meeting the following criteria:
- CD20/CD30 double-positive lymphomas
- Relapse after anti-CD19-CAR-T cell therapy, and CD20-positive lymphomas
- Never received anti-CD19-CAR-T cell therapy, CD20-positive lymphomas
- CD30-positive Hodgkin lymphoma.
- (5) Included lymphoma subtypes:
- DLBCL-NOS (Diffuse Large B-Cell Lymphoma, not otherwise specified)
- Primary mediastinal large B-cell lymphoma (PMBCL)
- Transformed follicular lymphoma (TFL), previously treated with follicular lymphoma chemotherapy, subsequently transformed into DLBCL, refractory disease
- Mantle cell lymphoma
- High-grade B-cell lymphoma
- Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
- Hodgkin lymphoma (HL).
- (6) ECOG performance status ≤2.
- (7) Expected survival of at least 12 weeks.
- (8) Adequate venous access (for single collection), and no other contraindications for blood cell separation.
- (9) Laboratory requirements at screening, with no hematologic evaluation within 7 days of receiving growth factors (long-acting granulocyte colony-stimulating factor (G-CSF/PEG-CSF) requires a 2-week interval):
- Absolute neutrophil count ≥1.0×10\^9/L;
- Hemoglobin ≥60 g/L (without red blood cell transfusion within 7 days);
- Platelets ≥50×10\^9/L (CLL indication unrestricted);
- Serum total bilirubin ≤1.5× upper limit of normal (ULN); or ≤3× ULN if liver tissue invasion by tumor;
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤2.5× ULN, AST/ALT ≤5× ULN if liver tissue invasion by tumor;
- Creatinine \<1.5× ULN and estimated glomerular filtration rate ≥60 mL/minute.
- (10) Left ventricular ejection fraction ≥45%, echocardiogram (ECHO) showing no clinically significant pericardial effusion (excluding minimal or physiological effusions), and no clinically significant findings on electrocardiogram.
- (11) Baseline oxygen saturation \>92% without supplemental oxygen.
- (12) Women of childbearing potential must have a negative serum or urine pregnancy test result (women who have undergone surgical sterilization or who are at least 2 years postmenopausal are not considered of childbearing potential).
Exclusion
- Here is the translation of the exclusion criteria for participants in a clinical study:
- Evidence of central nervous system lymphoma on brain MRI; active primary central nervous system DLBCL, unless CNS involvement has been effectively treated (i.e., participant is asymptomatic) and there has been a local treatment interval of \>4 weeks prior to enrollment.
- Active central nervous system diseases such as epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar diseases, or any autoimmune diseases with central nervous system involvement.
- History of or concurrent malignancies other than CD19+ malignancies.
- Clinically significant cardiac disease, or arrhythmias not controlled by medication.
- Presence or suspicion of uncontrolled fungal, bacterial, viral, or other infections requiring intravenous antibiotics; simple urinary tract infections and uncomplicated bacterial pharyngitis are allowed.
- Hepatitis B (positive hepatitis B surface antigen and hepatitis B DNA \>1000 copies/mL) and hepatitis C (positive hepatitis C antibody).
- Presence of any indwelling catheters or drainage tubes (e.g., percutaneous nephrostomy tube, Foley catheter, bile drainage tube, pleural/peritoneal/pericardial catheter); specialized central venous access devices like Port-A-Cath® or Hickman® catheters are allowed.
- Use of the following medications prior to:
- 1\) Ibrutinib within 1 day before apheresis. 2) Idelalisib (oral PI3Kδ inhibitor) within 2 days before apheresis. 3) Short-acting targeted therapy (such as tyrosine kinase inhibitors) within 72 hours before apheresis.
- 4\) Venetoclax (BCL-2 inhibitor) within 4 days before apheresis. 5) Long-acting growth factors (such as pegfilgrastim) within 14 days before apheresis, or short-acting growth factors or mobilizing agents (such as granulocyte colony-stimulating factor (G-CSF)/filgrastim) within 5 days before apheresis.
- 6\) Pharmacologic doses of corticosteroid therapy (\>5 mg/day prednisone or equivalent) and other immunosuppressive drugs within 7 days before enrollment.
- 7\) Radiotherapy within 14 days before enrollment. 8) Systemic cytotoxic drugs within 14 days before enrollment, including daily or weekly low-dose maintenance chemotherapy (e.g., cyclophosphamide, fludarabine, bendamustine, chlorambucil, methotrexate, vinblastine).
- If bridging therapy is administered post-apheresis, there must be at least a 7-day interval between bridging therapy and CAR-T cell infusion.
- 9\) Anti-PD1 or anti-PDL1 therapy within 4 weeks before enrollment. 10) Vaccination within 4 weeks before enrollment. 11) Donor lymphocyte infusion (DLI) within 4 weeks before enrollment. 12) Immunostimulatory or immunosuppressive therapy within 3 months before enrollment (such as interferon-α, interferon-β, IL-2, lenalidomide, efalizumab, alemtuzumab, cyclosporine, or methotrexate).
- (9) Active graft-versus-host disease (GVHD) using the CIBMTR acute GVHD grading system ≥ grade 2 or requiring systemic steroids greater than physiological doses.
- (10) History in the past 2 years of autoimmune diseases causing end-organ damage or requiring systemic immunosuppressive/disease-modifying agents, such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus.
- (11) History in the past 12 months of myocardial infarction, cardiac vascular procedures or stent implantation, unstable angina, or other clinically significant cardiac diseases.
- (12) History of genetic syndromes with bone marrow failure, such as Fanconi anemia, Costello syndrome, Shwachman-Diamond syndrome.
- (13) Symptomatic deep vein thrombosis or pulmonary embolism requiring systemic anticoagulation therapy within 6 months before enrollment. Subjects requiring prophylactic anticoagulation are allowed.
- (14) History of concurrent or prior malignancies (excluding basal cell carcinoma of the skin, in situ carcinoma of the breast/cervix, and other malignancies effectively controlled without treatment within the past five years).
- (15) Use of other investigational medicinal products within 30 days before screening.
- (16) Pregnant or lactating women of childbearing potential. Women who have undergone surgical sterilization or who are at least 2 years postmenopausal are not considered of childbearing potential.
- (17) Participants unwilling to use contraception from agreeing to treatment until completion of lymphocyte depletion chemotherapy or CAR-T cell infusion within 12 months (whichever is longer).
- (18) Any medical activities that could potentially interfere with the safety or efficacy evaluation of the study treatment.
- (19) According to the investigator's judgment, participants who are unlikely to complete all study visits or procedures required by the protocol (including follow-ups), or comply with the requirements of participating in the study.
Key Trial Info
Start Date :
July 31 2024
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
July 30 2027
Estimated Enrollment :
12 Patients enrolled
Trial Details
Trial ID
NCT06519344
Start Date
July 31 2024
End Date
July 30 2027
Last Update
July 25 2024
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