Safety and Efficacy of Early Second Infusion of Axi-cel Based on ctDNA for R/R Large B - Cell Lymphoma

Launched by ZHUJIANG HOSPITAL · Mar 24, 2025

Keywords

ClinConnect Summary

This clinical trial is looking at a new treatment approach for adults with a type of blood cancer called relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The study aims to find out if giving a second infusion of CAR T-cell therapy, which is a special treatment that uses the body’s own T-cells to fight cancer, can help patients achieve a complete remission (meaning no signs of cancer) faster and improve their long-term survival. Researchers will monitor the patients closely using blood tests and scans to check for cancer markers and assess their health during and after treatment.

To be eligible for this trial, participants need to be at least 18 years old and have been diagnosed with DLBCL or similar types of lymphoma that have not responded well to previous treatments. They should have a reasonable life expectancy and meet specific health criteria. If participants join the trial, they will receive treatment that includes collecting their T-cells, some chemotherapy to prepare their body, and potentially two infusions of CAR T-cells based on their test results. Throughout the study, participants will be monitored in the hospital for any side effects and will have regular follow-up appointments to ensure their safety and health.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Age ≥18 years, regardless of gender.
• • 2. Life expectancy \>12 weeks.
• • 3. ECOG performance status 0-2.
• 4. Histologically or cytologically confirmed B-cell non-Hodgkin lymphoma per WHO 2016 classification, including:
• • Diffuse large B-cell lymphoma (DLBCL) Primary mediastinal large B-cell lymphoma (PMBCL) Transformed follicular lymphoma (TFL) High-grade B-cell lymphoma (HGBCL).
• 5. Relapsed/refractory disease, defined as:
• • ≥1 prior relapse, Failure to achieve partial response (PR) after 2-3 cycles of first-line therapy, Failure to achieve complete response (CR) after 4-6 cycles of first-line therapy, Primary refractory disease, Secondary refractory disease, Disease progression following last line of therapy.
• 6. Adequate venous access for leukapheresis, with:
• • Hemoglobin ≥80 g/L, Absolute neutrophil count ≥1.0 ×10⁹/L, Platelet count ≥75 ×10⁹/L, OR parameters not meeting above thresholds but deemed acceptable for mononuclear cell collection per investigator's judgment.
• • 7. ≥1 measurable lesion per Lugano 2014 response criteria.
• 8. Organ function requirements:
• • Renal: Serum creatinine ≤2×ULN OR creatinine clearance ≥40 mL/min (Cockcroft-Gault formula).
• Cardiopulmonary:
• • Left ventricular ejection fraction (LVEF) \>50%, Baseline oxygen saturation \>92% on room air.
• Hepatic:
• • Total bilirubin ≤2×ULN (≤5×ULN in Gilbert syndrome), ALT/AST ≤3×ULN (≤5×ULN in patients with hepatic involvement).
• • 9. Negative serum pregnancy test for women of childbearing potential (WOCBP). Postmenopausal (≥2 years since last menses) or surgically sterilized women are exempt.
• 10. Within 60 days post-axi-cel:
• • Persistent ctDNA(+) or ctDNA(-→+) under CR or PET/CT-confirmed PR
• Exclusion Criteria:
• 1. History of malignancies other than DLBCL, PMBCL, TFL, or HGBCL within 5 years prior to screening, except:
• • Adequately treated carcinoma in situ of the cervix, Basal cell or squamous cell carcinoma of the skin, Localized prostate cancer after definitive resection, Ductal carcinoma in situ of the breast after curative surgery, Thyroid cancer after radical treatment.
• 2. Unstable systemic diseases, including but not limited to:
• • Active infections (excluding localized infections), Unstable angina, Cerebrovascular accident or transient ischemic attack (within 6 months prior to screening), Myocardial infarction (within 6 months prior to screening), Congestive heart failure (NYHA Class ≥III), Severe arrhythmia requiring pharmacologic management, Hepatic, renal, or metabolic disorders.
• 3. Conditions affecting informed consent or protocol compliance:
• • Physical or psychological disorders impairing the ability to provide written informed consent, Inability or unwillingness to comply with study requirements.
• • 4. Grade ≥3 cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) following prior axi-cel therapy.
• • 5. Active, uncontrolled serious infections.
• • 6. Uncontrolled active comorbidities that preclude study participation.
• • 7. Other conditions deemed by the investigator to confer unacceptable risk or render the patient ineligible.