Study to Evaluate the Efficacy of Axicabtagene Ciloleucel in Patients With Late Relapse of Diffuse Large B-Cell Lymphoma

NCT ID: NCT07254754

Last Updated: 2025-11-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

45 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-11-20

Study Completion Date

2031-12-31

Brief Summary

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Single-arm, open-label, multicenter, phase II trial aiming to include approximately 45 patients over 24 months. Patients will receive axicabtagene ciloleucel infusion and will be followed up to 5 years.

The total duration of the study is therefore of 7 years.

Detailed Description

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Axicabtagene Ciloleucel , an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, demonstrated a high rate of durable responses with a manageable safety profile, in patients with relapsed or refractory large B-cell lymphoma (LBCL) after two or more previous therapies. Recently, axicabtagene ciloleucel as demonstrated superior efficacy compared to standard of care (SOC) in 2nd line LBCL patients considered eligible for autologous stem-cell transplantation (ASCT) with primary refractory disease or early relapse (ZUMA-7). In this study, after a median follow-up of 24.9 months, the median event-free survival was 8.3 months in the axicabtagene ciloleucel group and 2.0 months in the standard-care group, and the 24-month event-free survival was 41% and 16%, respectively (hazard ratio, \[HR\] for event or death, 0.40; 95% confidence interval, 0.31 to 0.51; p\<0.001). Some response occurred in 83% of the patients in the axicabtagene ciloleucel group and in 50% of those in the SOC group (with a complete response \[CR\] in 65% and 32% of the patients, respectively). These data led to the approval of axicabtagene ciloleucel by the American and European regulatory agencies, for patients with LBCL refractory to first-line or relapsing within the first year after completion of induction immunochemotherapy.

More recently, the open-label phase 2 ALYCANTE trial assessed the safety and efficacy of axicabtagene ciloleucel as second-line therapy in patients with primary refractory or early relapsed aggressive B-cell lymphoma who were not deemed candidates for ASCT. Treatment with axicabtagene ciloleucel resulted in high response rates (best overall response 92.5%, best CR = 80.0%) and durable remissions (median PFS, 11 months, median overall survival \[OS\], not reached), with an acceptable safety profile in this population of patients considered unfit for ASCT.

The above-mentioned trials included only patients who were primary refractory or had relapsed within a year of completing first-line treatment. However, no data are available on the efficacy of axicabtagene ciloleucel in second line for patients relapsing more than one year after completion of induction. Although it is generally assumed that the outcome of these patients is better than that of patients showing early failure, still the outcome is not optimal at all, with at least half of the patients dying from the lymphoma in the next months. The current proposal is aimed at studying a possible role of axicabtagene ciloleucel in this subset of cases.

Conditions

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DIFFUSE LARGE B-CELL LYMPHOMA

Keywords

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lymphoma axicabtagene geltamo DIFFUSE LARGE B-CELL LYMPHOMA DLBCL RELAPSE

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Axicabtagene ciloleucel

Treatment consists of a single dose for infusion containing a dispersion for infusion of CAR-positive viable T cells in one infusion bag. The target dose is 2 × 106 CAR-positive viable T cells per kg of body weight (within a range of 1 × 10E6 - 2 × 10E6 cells/kg), with a maximum of 2 × 10E8 CAR-positive viable T cells for patients 100 kg and above.

Group Type EXPERIMENTAL

Axicabtagene Ciloleucel

Intervention Type DRUG

Treatment consists of a single dose for infusion containing a dispersion for infusion of CAR-positive viable T cells in one infusion bag. The target dose is 2 × 106 CAR-positive viable T cells per kg of body weight (within a range of 1 × 106 - 2 × 106 cells/kg), with a maximum of 2 × 108 CAR-positive viable T cells for patients 100 kg and above.

Interventions

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Axicabtagene Ciloleucel

Treatment consists of a single dose for infusion containing a dispersion for infusion of CAR-positive viable T cells in one infusion bag. The target dose is 2 × 106 CAR-positive viable T cells per kg of body weight (within a range of 1 × 106 - 2 × 106 cells/kg), with a maximum of 2 × 108 CAR-positive viable T cells for patients 100 kg and above.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Kite, A Gilead Company

INDUSTRY

Sponsor Role collaborator

Evidenze Health España (CRO)

UNKNOWN

Sponsor Role collaborator

Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mariana Bastos-Oreiro

Role: PRINCIPAL_INVESTIGATOR

Hospital General Universitario Gregorio Marañón

Alejandro Martín García-Sancho

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario Salamanca

Armando López-Guillermo

Role: PRINCIPAL_INVESTIGATOR

Hospital Clinic of Barcelona

Locations

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Complejo Hospitalario Universitario A Coruña

A Coruña, A Coruña, Spain

Site Status RECRUITING

Hospital Universitario Son Espases

Palma de Mallorca, Balearic Islands, Spain

Site Status RECRUITING

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, Spain

Site Status RECRUITING

Hospital Universitario de Salamanca

Salamanca, Castille and León, Spain

Site Status RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, Catalonia, Spain

Site Status RECRUITING

Hospital Clinic i Provincial de Barcelona

Barcelona, Catalonia, Spain

Site Status RECRUITING

Institut Català d'oncologia de L'Hospitalet

L'Hospitalet de Llobregat, Catalonia, Spain

Site Status RECRUITING

Hospital Universitario Donostia

San Sebastián, Gipuzkoa, Spain

Site Status RECRUITING

Complejo Hospitalario Universitario de Gran Canaria Dr. Negrín

Las Palmas de Gran Canaria, Las Palmas, Spain

Site Status RECRUITING

Hospital General Universitario Gregorio Marañón

Madrid, Madrid, Spain

Site Status RECRUITING

Hospital Universitario 12 de Octubre

Madrid, Madrid, Spain

Site Status RECRUITING

Hospital General Universitario Morales Meseguer

Murcia, Murcia, Spain

Site Status RECRUITING

Clínica Universidad de Navarra

Pamplona, Navarre, Spain

Site Status RECRUITING

Hospital Universitario Virgen del Rocío

Seville, Sevilla, Spain

Site Status RECRUITING

Hospital Clínico Universitario de Valencia

Valencia, Valencia, Spain

Site Status RECRUITING

Countries

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Spain

Central Contacts

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Auxi Moreno

Role: CONTACT

Phone: +34 683636850

Email: [email protected]

Ana María Méndez

Role: CONTACT

Email: [email protected]

Facility Contacts

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Sandra García Doval

Role: primary

Almudena Pérez Rodriguez

Role: backup

Mª Teresa Ros Matheu

Role: primary

Silvia Roig Juan

Role: backup

Alba del Río Manzano

Role: primary

Pilar González Echezarreta

Role: backup

Andrea Torices

Role: primary

Manuel Delgado

Role: backup

Alicia Nogueroles Olivares

Role: primary

Julia Sedó

Role: backup

Veronica Martil

Role: primary

Cecilia Vilas

Role: backup

Lydia Guillem

Role: primary

Mariona Guillamet

Role: backup

Nerea Castroagudín Romero

Role: primary

María Aurora Barbero Martínez

Role: backup

Elizabeth Alfonso Bermejo

Role: primary

Julia Wiedermann

Role: backup

Soraya Oviedo

Role: primary

Ana García

Role: backup

Alba Gutiérrez de la Peña

Role: primary

Paula Garcés

Role: backup

José Navarro Fernández

Role: primary

Josefa Gálvez Martínez

Role: backup

Andoni Urrutia

Role: primary

Sara Morales Espinosa

Role: backup

Rocío Jiménez

Role: primary

Estefanía Menéndez Pedregal

Role: backup

María Mercedes Bou Moreno

Role: primary

Carmen Hurtado Fontelles

Role: backup

Related Links

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Other Identifiers

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LATE-R-GEL-23

Identifier Type: -

Identifier Source: org_study_id