An Exploratory Clinical Study Evaluating the Safety and Efficacy of Intravenous Anti-CD20/CD30-CAR-T Cell Infusion in Relapsed/Refractory Lymphoma Patients.

NCT06519344 | Not Yet Recruiting Early Phase 1 DMC

• 1 other identifier: CD20/CD30-CN-A2
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

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+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 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).

  Up to 28 days from CAR-T infusion

Study Arms (1)

anti-CD20/CD30-CAR-T Cells

EXPERIMENTAL

anti-CD20/CD30-CAR-T cell infusion.Infusion doses:The planned infusion doses are follows：the first dose group at 3E5 cells/kg; the second dose group at 1E6 cells/kg; the third dose group at 3E6 cells/kg. Infusion doses refer to the number of CAR-positive cells. Administration method: anti-CD20/CD30-CAR-T cells are administered intravenously via an infusion pump at approximately 2-5 mL/minute, with a recommended infusion duration of less than 30 minutes.

Biological: anti-CD20/CD30-CAR-T Cells

Interventions

anti-CD20/CD30-CAR-T Cells BIOLOGICAL

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.

anti-CD20/CD30-CAR-T Cells

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (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

You may not qualify if:

• 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:
• \) 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.
• \) 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.
• \) Pharmacologic doses of corticosteroid therapy (\>5 mg/day prednisone or equivalent) and other immunosuppressive drugs within 7 days before enrollment.
• \) 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.
• \) 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.

Sponsors & Collaborators

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

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: July 19, 2024
• First Posted: July 25, 2024
• Study Start: July 31, 2024
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): July 30, 2027
• Last Updated: July 25, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share