B Cell Malignancies
Conditions
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 study phase,a traditional 3+3trial design is employed for dose escalation.
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 aims to include patients with CD20/CD30 double-positive relapsed/refractory lymphomas, CD20-positive relapsed/refractory B-cell lymphomas (including patients who have relapsed after anti-CD19-CAR-T cell therapy), and CD30-positive Hodgkin lymphoma. Participants will undergo screening, peripheral blood mononuclear cell (PBMC) collection, and lymphocyte depletion pre-treatment before receiving a single infusion of anti-CD20/CD30-CAR-T cells. Throughout the study, efficacy assessments will occur at baseline and at 4 weeks post-treatment, and subsequently at 3 months, 6 months, 9 months, and 12 months, until disease progression (PD), relapse, change of treatment regimen, death, intolerable toxicity, investigator decision, or voluntary withdrawal (whichever comes first). Safety evaluations of anti-CD20/CD30-CAR-T cell therapy will be conducted according to the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) by laboratory tests, 12-lead electrocardiograms, vital signs, and physical examinations. Additionally, blood samples will be collected to assess cellular pharmacokinetics and explore the effects of cellular therapy on ferritin, C-reactive protein, and related cytokines. The study is designed as an exploratory research project, subject to implementation conditions at the research center. Dose escalation during this study phase will follow a traditional 3+3 trial design.
Interventions
BIOLOGICALanti-CD20/CD30-CAR-T Cells
Before cell infusion,researchers 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-CD20/CD30-CAR-T cell infusion,including blood transfusions and blood products, antibiotic therapy, antiemetics, antidiarrheals, analgesice,etc.
Sponsors
Shanghai Tongji Hospital, Tongji University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
(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: 1. 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. 2. 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. 3. 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 criteria
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Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose-limiting toxicity | Up to 28 days from CAR-T infusion | The proportion of patients receiving CAR-T cells who encounter dose-limiting toxicities(DLTs). Safety evlauations 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). |
Contacts
Primary ContactAibin Liang
Backup ContactPing LI
Outcome results
None listed