Evaluating early second infusion of CAR T-cell therapy for lymphoma

A Prospective, Single - Arm Clinical Study on the Safety and Efficacy of Early Second Infusion of CD19 CAR - T Based on ctDNA Monitoring in the Treatment of Relapsed/Refractory Large B - Cell Lymphoma

This study is testing if giving a second dose of CAR T-cell therapy earlier can help adults with tough-to-treat lymphoma feel better and live longer.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Zhujiang Hospital (Academic / other)
• Drugs / interventions: CAR T, CAR-T, chemotherapy, cyclophosphamide, fludarabine
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06902012 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to assess the safety and efficacy of an early secondary infusion of CD19 CAR T-cell therapy in adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), using ctDNA monitoring to guide treatment decisions. Participants will undergo leukapheresis to collect T cells, followed by preconditioning chemotherapy and two CAR T infusions if ctDNA remains positive. The study will monitor the participants for adverse events and measure outcomes such as complete remission rates and long-term survival. It is a single-arm, single-center, prospective study enrolling 15 eligible patients.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with relapsed or refractory DLBCL who have failed prior therapies.

Not a fit: Patients with non-B-cell lymphomas or those who are not eligible for CAR T-cell therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to improved remission rates and survival outcomes for patients with relapsed/refractory DLBCL.

How similar studies have performed: Other studies have shown promising results with CAR T-cell therapies in similar patient populations, indicating potential for success with this approach.

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.

Where this trial is running

Guangzhou, Guangdong

• Zhujiang Hospital — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: Sanfang Tu, Doctor

Conditions Relapsed/Refractory Diffuse Large B-cell Lymphoma; CAR-T; LYMPHOMA; SENCOND INFUSION