Study of Axicabtagene Ciloleucel Versus Standard of Care Therapy as First-line in Subjects With High-Risk Large B-Cell Lymphoma

JRCT ID: jRCT2023240034

Registered date:17/10/2024

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: High-Risk Large B-Cell Lymphoma
• Date of first enrollment: 01/11/2024
• Target sample size: 300
• Countries of recruitment: North America,Japan,EU,Japan,Australia,Japan
• Study type: Interventional

Intervention(s)

Subjects in the axicabtagene ciloleucel treatment arm will receive a single infusion of axicabtagene ciloleucel.
Subjects in the SOCT arm will receive the investigator's choice of either rituximab plus CHOP, or dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab

Outcome(s)

• Primary Outcome: Event Free Survival (EFS) by blinded central assessment

Secondary Outcome

- Progression Free survival (PFS) by blinded central assessment
- Overall survival (OS)
- PFS by investigator assessment
- Complete remission (CR) rate by blinded central assessment
- Incidence of AEs, SAEs, deaths, and clinically significant changes in safety laboratory values
- Patient reported quality of life (PRO-QOL) as measured by EORTC QLQ-C30, EORTC QLQ-NHL-HG29, and EQ-5D-5L

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable

Include criteria

1) High-risk disease defined as an International prognostic index (IPI) score of 4 or 5 at initial diagnosis
2) Histologically confirmed large B-cell Lymphoma (LBCL) based on 2016 World Health Organization (WHO) classification by local pathology lab assessment, including one of the following:
a.Diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS)
b.High-grade B-cell lymphoma (HGBL) (including HGBL with MYC and BCL2 and/or BCL6 rearrangements (DHL/THL) based on FISH analysis, and HGBL-NOS). Please note that FISH testing must be performed for all potential patients.
Note: Transformed DLBCL from follicular lymphoma or from marginal zone lymphoma is eligible if the subject has not received treatment with an anthracycline-containing regimen
3) Have received only 1 cycle of R-chemoimmunotherapy
4) Age >= 18
5) ECOG 0-2 at the time of randomization (ECOG >2 at the time of diagnosis is acceptable)
6) Ann Arbor Stage III or IV disease
7) Adequate organ and bone marrow function

Exclude criteria

1) The following WHO 2016 subcategories by local assessment
a.T-cell/histiocyte-rich LBCL
b.Primary DLBCL of the Central Nervous system (CNS)
c.Primary mediastinal (thymic) LBCL
d.B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma
e.Burkitt lymphoma
f.History of Richter's transformation of chronic lymphocytic leukemia
2) CNS or cardiac involvement with lymphoma
3) Any prior treatment for LBCL other than the 1 cycle of R-chemoimmunotherapy
4) Active infection with Hepatitis B or Hepatitis C (history of infection is acceptable as long as viral load is undetectable)
5) Positive for human immunodeficiency virus (HIV) unless taking appropriate anti-HIV medications, with an undetectable viral load by Polymerase chain reaction (PCR) and with a CD4 count > 200 cells/uL
6) Any medical condition requiring maintenance systemic immunosuppression and/or systemic disease-modifying agents within the last 2 years (endocrine conditions that require maintenance with physiologic dose steroids are allowed).
7) CNS disorder, including stroke or transient ischemic attacks, within 12 months
8) Clinically significant cardiac disorder, including myocardial infarction or unstable angina, within 12 months
9) Non-line associated, Grade 2 or greater, deep vein thrombosis or pulmonary embolism requiring therapeutic anticoagulation within 6 months of randomization
10) Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Simple bacterial infections are permitted if responding to treatment. Discussion with Kite medical monitor is encouraged
11) Any medical condition or residual toxicities from prior therapies per investigator assessment likely to interfere with assessment of safety or efficacy of treatment
12) History of malignancy other than non-melanoma skin cancer or carcinoma in situ (eg. cervix, bladder, breast) unless disease free for at least 3 years
13) History of autologous or allogenic stem cell transplant (SCT)

Related Information

• Primary Sponsor: Asou Hiroya
• Secondary ID(s): NCT05605899,2022-501489-24-00