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

NCT06902012 | Recruiting Phase 1

• 1 other identifier: 2024-KY-343-01
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate the efficacy and safety of early secondary infusion of CD19 CAR T-cell therapy in adults with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), guided by ctDNA monitoring. The main questions it aims to answer are:

• Leukapheresis to collect T cells for CAR-T manufacturing.
• Preconditioning chemotherapy (fludarabine and cyclophosphamide) to prepare the body for CAR-T infusion.
• Two CD19 CAR-T infusions: The first infusion (2×10⁶ cells/kg) followed by a second infusion (same dose) if ctDNA remains positive when PET/CT shows CR or PET/CT shows PR within 60 days post-first infusion. Participants will undergo:
• Frequent hospital monitoring for ≥14 days post-infusion to manage potential toxicities.
• Regular follow-ups (e.g., blood tests, ctDNA analysis, PET/CT scans) at scheduled intervals up to 12 months.
• Continuous safety assessments, including CRS grading, neurological evaluations, and infection monitoring.

Conditions

Relapsed/Refractory Diffuse Large B-cell Lymphoma

Keywords

CAR-T; LYMPHOMA; SENCOND INFUSION

Outcome Measures

Primary Outcomes (1)

• complete response rate

  the proportion of subjects achieving CR as assessed by the Lugano 2014 criteria (Cheson et al., 2014).

  3 months after CAR-T infusion

Study Arms (1)

Single-Arm Group

EXPERIMENTAL

All participants receive early second CAR-T infusion based on ctDNA monitoring.

Drug: Infusion of Axicabtagene Ciloleucel

Interventions

Infusion of Axicabtagene Ciloleucel DRUG

Drug: Axicabtagene Ciloleucel (CD19 CAR-T cells), 2×106 cells/kg, IV infusion at Day 0 and 30-90 days post-first infusion. Drug: Cyclophosphamide (500 mg/m²) + Fludarabine (30 mg/m²), IV on Days -5, -4, -3. Procedure: ctDNA monitoring via liquid biopsy at pre-lymphodepletion and Months 1, 2, 3, 6, 9, 12 post-infusion.

Single-Arm Group

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years, regardless of gender.
• Life expectancy \>12 weeks.
• ECOG performance status 0-2.
• 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).
• 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.
• 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.
• ≥1 measurable lesion per Lugano 2014 response criteria.
• 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:

You may not qualify if:

• 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.
• 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.
• 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.
• Grade ≥3 cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) following prior axi-cel therapy.
• Active, uncontrolled serious infections.
• Uncontrolled active comorbidities that preclude study participation.
• Other conditions deemed by the investigator to confer unacceptable risk or render the patient ineligible.

Sponsors & Collaborators

• Zhujiang Hospital: lead

Study Sites (1)

Zhujiang Hospital

Guangzhou, Guangdong, 510282, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Sanfang Tu, Doctor

CONTACT

86 13430200803; doctortutu@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2025
• First Posted: March 30, 2025
• Study Start (Estimated): February 1, 2027
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: March 30, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

CN (1)