Axicabtagene ciloleucel for adults with late-relapsing diffuse large B‑cell lymphoma

LATE-R Trial. A Phase II, Single-Arm, Open-Label, Multicenter Study to Evaluate the Efficacy of Axicabtagene Ciloleucel in Patients With Late Relapse of Diffuse Large B-Cell Lymphoma

This trial will try axicabtagene ciloleucel (a CD19 CAR‑T cell therapy) in adults with diffuse large B‑cell lymphoma who have a late relapse after initial treatment.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 45 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea (other)
• Drugs / interventions: rituximab, obinutuzumab, tocilizumab, CAR-T, CAR T, chemotherapy, immunotherapy, radiation, cyclophosphamide, fludarabine, chimeric antigen receptor
• Locations: 15 sites (A Coruña, A Coruña and 14 other locations)
• Trial ID: NCT07254754 on ClinicalTrials.gov

What this trial studies

This is a single‑arm, open‑label, multicenter phase II trial that plans to enroll about 45 patients over 24 months to receive a single infusion of axicabtagene ciloleucel and be followed for up to five years. Eligible patients must have PET‑positive relapsed or refractory aggressive B‑cell lymphoma (including DLBCL, high‑grade B‑cell lymphoma, or transformed follicular lymphoma Grade 3B), prior anti‑CD20 therapy and CHOP‑like chemotherapy, and meet other clinical criteria; primary mediastinal B‑cell lymphoma is excluded. The trial will be conducted at three university hospitals in Spain and will collect efficacy and safety outcomes over long‑term follow‑up, with a total study duration of about seven years. Axicabtagene ciloleucel is an anti‑CD19 CAR‑T therapy with prior evidence of durable responses in relapsed/refractory large B‑cell lymphoma.

Who should consider this trial

Good fit: Adults (≥18 years) with PET‑positive relapsed or refractory aggressive B‑cell lymphoma (DLBCL, HGBL, or transformed FL Grade 3B) who previously received an anti‑CD20 antibody and CHOP‑like chemotherapy and can attend a participating center are ideal candidates.

Not a fit: Patients with primary mediastinal B‑cell lymphoma, PET‑negative disease, inadequate prior therapy, or significant comorbidities that make CAR‑T therapy unsafe are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, this could provide a durable remission option for patients with late‑relapsing DLBCL who have limited standard treatments.

How similar studies have performed: Prior trials such as ZUMA‑7 and ALYCANTE have shown that axicabtagene ciloleucel can produce higher response rates and longer event‑free survival than standard care in certain relapsed/refractory large B‑cell lymphoma populations.

Eligibility criteria

Inclusion Criteria:

1. Signed written Informed Consent Form
2. Age \> 18 years
3. Patient who understands and speaks one of the country official languages
4. Histologically proven relapsed or refractory aggressive B-cell non-Hodgkin lymphoma (B-NHL) of the following histology at relapse: diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBL) and follicular lymphoma Grade 3B per WHO 2016 classification. Indolent B-NHL who transformed into aggressive B-NHL and were previously treated with R-CHOP-like after transformation are eligible. Primary mediastinal B-cell lymphoma are not eligible.
5. Positron-emission tomography (PET)-positive disease
6. Patients must have received adequate first-line therapy including at a minimum:

   * An anti-CD20 monoclonal antibody (rituximab or obinutuzumab), and
   * CHOP or CHOP-like chemotherapy Note: CHOP-like chemotherapy corresponds to ACVBP, EPOCH, or COPADEM. Dose-reduced CHOP (i.e., miniCHOP) is excluded except for dose-reductions of vincristine due to peripheral neuropathy. Patients who have received additional drugs in combination with CHOP or CHOP-like regimen are eligible.
7. Relapsed disease after first line chemo immunotherapy (full dose of R-CHOP or R-CHOP-like regimen), documented by PET-scan and biopsy:

   • Relapsed disease defined as complete remission to first-line therapy followed by biopsy-proven disease relapse after 12 months and up to 5 years from end of first-line therapy.
8. Patients must meet CAR-T-eligible criteria as defined by:

   * Patient deemed eligible for CAR T-cells therapy by the CAR-T physician
   * AND all the following criteria:

     * ECOG performance status of 0, 1 or 2
     * Adequate vascular access for leukapheresis procedure (either peripheral or central venous line)
     * Absolute neutrophil count (ANC) ≥ 1 x 109/L
     * Platelets ≥ 75 x 109/L
     * Absolute lymphocyte count ≥ 0.1 x 109/L
     * Creatinine clearance (CrCl) as estimated by Cockcroft Gault or MDRD ≥ 40 mL/min
     * Serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ≤ 2.5xULN
     * Total bilirubin \<1.5 mg/dL, except in patients with Gilbert's syndrome
     * Cardiac ejection fraction ≥ 45%
     * Baseline oxygen saturation ≥ 92% on room air
9. Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 12 months are not considered to be of childbearing potential).

Exclusion Criteria:

1. Patients who received more than one prior line of systemic therapy
2. Early relapsed disease defined as complete remission to first-line therapy followed by biopsy-proven disease relapse before 12 months from end of first-line therapy.
3. Refractory disease defined as:

   * Progressive disease (PD) during first-line therapy
   * Stable disease (SD) as best response after at least 4 cycles of first-line therapy (e.g., 4 cycles of R-CHOP)
   * Partial response (PR) as best response after at least 6 cycles, and biopsy-proven residual disease
4. Patients who received first line of R-CHOP or obinutuzumab-CHOP for an indolent B-NHL who relapse as transformed aggressive B-NHL after a year from the end of first-line therapy are NOT eligible.
5. Prior CD19 targeted therapy
6. Patients with cardiac atrial or cardiac ventricular lymphoma involvement
7. Requirement for urgent therapy due to tumor mass effects, such as bowel obstruction or blood vessel compression
8. Patient with clinically significant pleural effusion
9. History of another primary malignancy that has not been in remission for at least 3 years (except for nonmelanoma skin cancer or carcinoma in situ (eg, cervix, bladder, breast)). A maintenance treatment is not allowed.
10. Patients with detectable Central Nervous System (CNS) lymphoma. Patients with a history of CNS lymphoma but no active CNS disease (after systematic MRI and lumbar puncture) at the time of enrolment will be eligible.
11. Presence of CNS disorder such as dementia, autoimmune disease with CNS involvement, cerebral edema with confirmed structural defects by appropriate imaging, or seizure disorders requiring active anticonvulsive medication. History of stroke, transient ischemic attack, or posterior reversible encephalopathy syndrome (PRES) within 12 months prior to enrolment.
12. Presence of any indwelling line or drain (eg, percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter). Ommaya reservoirs and dedicated central venous access catheters, such as a Port-a-Cath or Hickman catheter, are permitted.
13. History of acute or chronic active hepatitis B or C infection (seropositivity). If there is a positive history of treated hepatitis B or hepatitis C (negative HBsAg and positive Anti-HBc/ positive anti-HCV), the viral load HBV DNA/ HCV RNA) must be undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing
14. Positive for human immunodeficiency virus (HIV) unless taking appropriate anti-HIV medications, with an undetectable viral load by PCR and with a CD4 count \> 200 cells/uL.
15. Uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antimicrobials or other treatment at the time of leukapheresis or axicabtagene ciloleucel administration
16. History of any one of the following cardiovascular conditions within the past 12 months: Class III or IV heart failure as defined by the New York Heart Association, cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease
17. Presence of primary immunodeficiency
18. History of any medical condition including but not limited to autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression and/or systemic disease modifying agents within the last year. Endocrine conditions that require maintenance with physiologic dose steroids are allowed.
19. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis per chest computed tomography (CT) scan at screening. History of radiation pneumonitis in the radiation field (fibrosis) is allowed.
20. History of severe immediate hypersensitivity reaction to tocilizumab or any of the agents used in this study
21. History of severe, immediate hypersensitivity reaction attributed to aminoglycosides, cyclophosphamide or fludarabine
22. Treatment with a live, attenuated vaccine within 6 weeks prior to initiation of study treatment or anticipation of need for such a vaccine during the study
23. Women of childbearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of lymphodepletion chemotherapy on the fetus or infant.
24. Patients of either sex who are not willing to practice birth control from the time of consent during treatment and for at least 12 months after conditioning chemotherapy dosing or axicabtagene ciloleucel dosing, whichever is later
25. In the investigator's judgment, the patient is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation
26. Adult person unable to provide informed consent because of intellectual impairment, any serious medical condition, laboratory abnormality or psychiatric illness.

Where this trial is running

A Coruña, A Coruña and 14 other locations

• Complejo Hospitalario Universitario A Coruña — A Coruña, A Coruña, Spain (RECRUITING)
• Hospital Universitario Son Espases — Palma de Mallorca, Balearic Islands, Spain (RECRUITING)
• Hospital Universitario Marqués de Valdecilla — Santander, Cantabria, Spain (RECRUITING)
• Hospital Universitario de Salamanca — Salamanca, Castille and León, Spain (RECRUITING)
• Hospital Universitari Vall d'Hebron — Barcelona, Catalonia, Spain (RECRUITING)
• Hospital Clinic i Provincial de Barcelona — Barcelona, Catalonia, Spain (RECRUITING)
• Institut Català d'oncologia de L'Hospitalet — L'Hospitalet de Llobregat, Catalonia, Spain (RECRUITING)
• Hospital Universitario Donostia — San Sebastián, Gipuzkoa, Spain (RECRUITING)
• Complejo Hospitalario Universitario de Gran Canaria Dr. Negrín — Las Palmas de Gran Canaria, Las Palmas, Spain (RECRUITING)
• Hospital General Universitario Gregorio Marañón — Madrid, Madrid, Spain (RECRUITING)
• Hospital Universitario 12 de Octubre — Madrid, Madrid, Spain (RECRUITING)
• Hospital General Universitario Morales Meseguer — Murcia, Murcia, Spain (RECRUITING)
• Clínica Universidad de Navarra — Pamplona, Navarre, Spain (RECRUITING)
• Hospital Universitario Virgen del Rocío — Seville, Sevilla, Spain (RECRUITING)
• Hospital Clínico Universitario de Valencia — Valencia, Valencia, Spain (RECRUITING)

Study contacts

• Principal investigator: Mariana Bastos-Oreiro — Hospital General Universitario Gregorio Marañón
• Study coordinator: Auxi Moreno

Conditions: DIFFUSE LARGE B-CELL LYMPHOMA, lymphoma, axicabtagene, geltamo, DLBCL, RELAPSE