Safety and Efficacy of Anti-CD20/CD30 CAR-T Cells in Subjects with Relapsed/Refractory Lymphoma

Last updated: September 4, 2024
Sponsor: Shanghai First Song Biotechnology Co., LTD
Overall Status: Active - Recruiting

Phase

1

Condition

Lymphoma

Treatment

anti-CD20/CD30-CAR-T cells

Cyclophosphamide

Fludarabine

Clinical Study ID

NCT06532643
CD20/CD30-CN-A1
  • Ages 14-70
  • All Genders

Study Summary

This study is an exploratory clinical trial of a single-center, open-label, single-dose treatment of anti-CD20/CD30-CAR-T cells in subjects with relapsed/refractory lymphoma.

Eligibility Criteria

Inclusion

Inclusion Criteria

  • Patients must meet all of the following criteria to be eligible for the study:
  1. Voluntarily participate in the clinical study. The individual or the legalguardian fully understands the study, sign the informed consent form (ICF), andis willing and able to follow and complete all trial procedures.

  2. Age ≥ 14 years and < 70 years.

  3. Subjects with refractory or relapsed disease after current standard treatments (including allogeneic or autologous hematopoietic stem cell transplantation)who are not suitable for other treatment options, such as a second stem celltransplant. The definitions of relapsed/refractory lymphoma include one of thefollowing situations:

  4. No response to first-line treatment (primary refractory disease, excludingparticipants intolerant to first-line treatments).

  • Disease progression (PD) as assessed after first-line treatment.
  • Best efficacy of first-line treatment (e.g., 4 cycles of RCHOP) asstable disease (SD), with the duration of SD not exceeding 6 monthsafter the last dose.
  1. No response to second-line or more treatments.
  • PD being the best response to the most recent treatment.
  • Best efficacy of the last line of treatment as SD after at least 2cycles, with the duration of SD not exceeding 6 months after the lastdose.
  1. Refractory after autologous stem cell transplant (ASCT).
  • Disease progression or relapse ≤ 12 months post-ASCT (relapsedpatients must have biopsy-proven relapse).
  • If salvage treatment is administered after ASCT, the subjects mustnot have had a response or relapse after the last line of treatment.
  • Relapsed or refractory disease after two or more lines of systemictreatment.
  1. Lymphoma patients must have target antigens meeting the following criteria:

  2. CD20/CD30 double-positive expressing lymphoma.

  3. Relapse after receiving anti-CD19-CAR-T cell therapy, with CD20 positivelymphoma.

  4. CD20 positive lymphoma that has not previously received anti-CD19-CAR-Tcell therapy.

  5. CD30 positive Hodgkin lymphoma.

  6. Subtypes of lymphoma included for enrollment are as follows:

  7. DLBCL-NOS (diffuse large B-cell Lymphoma, not otherwise specified)

  8. Primary mediastinal B-cell lymphoma (PMBCL)

  9. Transformed follicular lymphoma (TFL), previously treated for follicularlymphoma and then transformed to refractory DLBCL

  10. Mantle cell lymphoma

  11. High-grade B-cell lymphoma

  12. Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)

  13. Hodgkin lymphoma (HL)

  14. ECOG performance status ≤ 2.

  15. Expected survival of at least 12 weeks.

  16. Adequate venous access (for apheresis) and no other contraindications for bloodcell separation.

  17. Laboratory tests during screening must meet the following requirements, and thehematological assessment must not have received cell growth factors within 7days (long-acting colony-stimulating factors (G-CSF/PEG-CSF) require a 2-weekinterval) or platelet transfusions:

  18. Absolute neutrophil count ≥ 1.0×10^9/L.

  19. Hemoglobin ≥ 60 g/L (without red blood cell transfusion in the last 7days).

  20. Platelets ≥ 50×10^9/L (unrestricted for CLL indications).

  21. Total bilirubin ≤ 1.5× the upper limit of normal (ULN); or total bilirubin ≤ 3× ULN when the tumor invades liver tissue.

  22. Aspartate transaminase (AST), alanine transaminase (ALT) ≤ 2.5×ULN, withAST/ALT ≤ 5×ULN when the tumor invades liver tissue.

  23. Creatinine < 1.5× ULN and estimated creatinine clearance ≥ 60 mL/min.

  24. Ejection fraction ≥ 45%, with echocardiogram (ECHO) confirming no pericardialeffusion (excluding small or physiological amounts), and electrocardiogramresults with no clinical significance.

  25. Baseline oxygen saturation > 92% without supplemental oxygen.

  26. Women of childbearing potential must have a negative serum or urine pregnancytest result (women who have undergone surgical sterilization or have beenpostmenopausal for at least 2 years are not considered of childbearingpotential).

Exclusion

Exclusion Criteria:

  • Subjects are not eligible to participate in this study if they meet any of thefollowing criteria:
  1. MRI of the brain shows evidence of central nervous system lymphoma; activeprimary central nervous system DLBL, unless central nervous system involvementhas been effectively treated (i.e., participant is asymptomatic), and there hasbeen more than a 4-week gap since local treatment.

  2. Active central nervous system diseases, such as epilepsy, cerebrovascularischemia/hemorrhage, dementia, cerebellar diseases, or any autoimmune diseaseswith central nervous system involvement.

  3. History of or concurrent diagnosis of malignancies other than CD19+malignancies.

  4. Clinically significant heart disease or arrhythmias that cannot be controlledwith medication.

  5. Presence or suspicion of fungal, bacterial, viral, or other infections that areuncontrolled or require intravenous antibiotics for treatment; uncomplicatedurinary tract infections and uncomplicated bacterial pharyngitis are allowed.

  6. Positive for hepatitis B (HBsAg positive and HBV DNA >1000 copies/mL) andhepatitis C (positive for HCV antibodies); syphilis or human immunodeficiencyvirus (HIV) infection.

  7. Presence of any indwelling catheter or drainage tube (such as percutaneousnephrostomy, indwelling Foley catheter, bile drainage tube, orpleural/peritoneal/pericardial catheter); use of specialized central venousaccess devices like Port-A-Cath® or Hickman® catheters is allowed.

  8. History of using any of the following medications:

  9. Lenalidomide within 1 day before the apheresis.

  10. Idelalisib (oral PI3Kδ inhibitor) within 2 days before the apheresis.

  11. Short-acting targeted therapy (like tyrosine kinase inhibitors) within 72hours before the apheresis.

  12. Venetoclax (BCL-2 inhibitor) within 4 days before the apheresis.

  13. Long-acting growth factors (like pegylated filgrastim) within 14 daysbefore the apheresis, or short-acting growth factors or mobilizationagents (like G-CSF/filgrastim, plerixafor) within 5 days before theapheresis.

  14. Pharmacological doses of corticosteroids (>5mg/day of prednisone orequivalent doses of other corticosteroids) or other immunosuppressiveagents within 7 days before enrollment.

  15. Radiation therapy within 14 days before enrollment.

  16. Systemic cytotoxic drugs, including low-dose maintenance chemotherapy (cyclophosphamide, ifosfamide, bendamustine, methotrexate, ormercaptopurine, vincristine, etc.), within 14 days before enrollment. Ifbridging therapy is given after apheresis, there should be more than a 7-day gap between bridging therapy and CAR-T cell infusion.

  17. Anti-PD1 or anti-PDL1 within 4 weeks prior to enrollment.

  18. Live vaccines within 4 weeks prior to enrollment.

  19. Donor lymphocyte infusion (DLI) within 4 weeks prior to enrollment.

  20. Immune stimulation or immunosuppressive therapy (like interferon-α,interferon-β, IL-2, etanercept, infliximab, tacrolimus, cyclosporine, ormycophenolate mofetil) within 4 weeks prior to enrollment.

  21. Use of clofarabine or cladribine within 3 months prior to enrollment, oruse of PEG-asparaginase within 3 weeks prior to enrollment.

  22. Active graft-versus-host disease (GVHD) rated ≥2 on the CIBMTR acute GVHDgrading system or requires systemic steroids at doses greater thanphysiological levels.

  23. A history of autoimmune diseases in the past 2 years (like Crohn's disease,rheumatoid arthritis, or systemic lupus erythematosus) that has caused damageto end organs or requires systemic immunosuppression/systemic disease-modifyingagents.

  24. A history of myocardial infarction, cardiac angioplasty or stenting, unstableangina, or other clinically significant heart diseases within the 12 monthsprior to enrollment.

  25. A history of genetic syndromes associated with bone marrow failure, such asFanconi anemia, Kostmann syndrome, or Schwachman-Diamond syndrome.

  26. A history of symptomatic deep vein thrombosis or pulmonary embolism requiringsystemic anticoagulation in the 6 months before enrollment. Subjects need to beon preventive anticoagulant medication.

  27. A history of other malignancies (except for non-melanoma skin cancer, in situbreast/cervical cancer, and other malignant tumors that have been effectivelycontrolled without treatment in the past five years).

  28. Use of other investigational medicinal products within 30 days prior toscreening.

  29. Pregnant or breastfeeding women of childbearing age. Women who have undergonesurgical sterilization or are postmenopausal for at least 2 years are notconsidered of childbearing potential.

  30. Male and female subjects unwilling to practice contraception from the time theyagree to treatment until 12 months after completing the lymphodepletingchemotherapy or CAR-T infusion (whichever is longer).

  31. Any medical activities that could interfere with the safety or efficacyevaluation of the study treatment.

  32. In the judgment of the investigator, subjects are unlikely to complete allrequired study visits or procedures (including follow-ups) or to comply withthe study participation requirements.

Study Design

Total Participants: 9
Treatment Group(s): 3
Primary Treatment: anti-CD20/CD30-CAR-T cells
Phase: 1
Study Start date:
August 24, 2023
Estimated Completion Date:
September 01, 2026

Study Description

The study will enroll subjects with CD20 and CD30-positive lymphoma, CD20-positive lymphoma, or CD30-positive Hodgkin lymphoma. Subjects will receive a single infusion of anti-CD20/CD30-CAR-T cells after screening, PBMC collection, and lymphodepleting chemotherapy. Toxicity will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) from the National Cancer Institute. Safety of anti-CD20/CD30-CAR-T cell therapy will be evaluated through laboratory tests, including 12-lead electrocardiograms, vital sign checks, etc. Additionally, blood samples will be collected from subjects to study cellular pharmacokinetics and explore the effects of cell therapy on ferritin, C-reactive protein, and related cytokines.

Connect with a study center

  • The First Affiliated Hospital of Anhui Medical University

    Hefei, Anhui 230022
    China

    Active - Recruiting

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