Study to Compare Axicabtagene Ciloleucel With Standard of Care Therapy as First-line Treatment in Participants With High-risk Large B-cell Lymphoma (ZUMA-23)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Kite Pharma Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

28 Mar 2025 → ongoing

Decision date (initial)

2023-09-04

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Kite Pharma, Inc. United States

External identifiers

EU CT number

2022-501489-24-00

ClinicalTrials.gov

NCT05605899

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy, Pharmacodynamic

To compare the efficacy of axicabtagene ciloleucel versus standard of care therapy (SOCT), as measured by event-free survival (EFS).

Secondary objectives 4

1. To compare the efficacy of axicabtagene ciloleucel versus SOCT, as measured by progression-free survival (PFS) and overall survival (OS).
2. To compare the efficacy of axicabtagene ciloleucel versus SOCT, as measured by PFS and complete remission (CR) rate.
3. To compare the safety of axicabtagene ciloleucel versus SOCT.
4. To compare quality of life (QOL) of axicabtagene ciloleucel versus SOCT.

Conditions and MedDRA coding

First-line treatment of adult subjects with high-risk large B-cell lymphoma (LBCL) including diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) and high-grade B-cell lymphoma (HGBL).

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. High-risk disease defined as an IPI score of 4 or 5 at initial diagnosis
2. Histologically confirmed 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, 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) Note: Transformed DLBCL from follicular lymphoma or from marginal zone lymphoma is eligible if no prior treatment with anthracycline-containing regimen.
3. Ann Arbor Stage III or IV disease.
4. Have received only 1 cycle of R-chemotherapy
5. At least 1 measurable lesion per the Lugano Classification {Cheson 2014} on anatomical imaging such as computed tomography (CT) imaging (functional imaging such as PET may not be used to identify a measurable lesion). A measurable lesion is defined as greater than 1.5 cm LDi for lymph node and greater than 1.0 cm LDi for extranodal lesion
6. Adequate tumor biopsy specimen available for central pathology review (detailed sample collection requirement is in central pathology laboratory manual).
7. Age 18 years or older.
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at the time of randomization. Note: ECOG > 12 at diagnosis is acceptable.
9. Adequate bone marrow, renal, hepatic, pulmonary, and cardiac function as indicated by: a) Absolute neutrophil count (ANC) ≥ 1000/μL b) Platelet count ≥ 75,000/μL c) Absolute lymphocyte count ≥ 100/μL d) Creatinine clearance (as estimated by any local institutional method) ≥ 60 mL/minute e) Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels ≤ 2.5 × upper limit of normal (ULN) or ≤ 5 x ULN if documented liver involvement of lymphoma f) Total bilirubin ≤ 1.5 mg/dL, except in subjects with Gilbert’s Syndrome or documented LBCL liver or pancreatic involvement where ≤ 3.0 times the ULN g) Left ventricular ejection fraction (LVEF) ≥ 50% and no evidence of clinically significant pericardial effusion, and no clinically significant abnormal electrocardiogram (ECG) findings h) No evidence of Grade 2 (per Common Terminology Criteria for Adverse Events [CTCAE] 5.0) or greater pleural effusion or ascites (subjects with Grade 1 ascites or pleural effusion are eligible) i) Baseline oxygen saturation > 92% on room air
10. 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 2 years are not considered to be of childbearing potential).

Exclusion criteria 22

1. Any prior treatment for LBCL other than the 1 cycle of R-chemotherapy.
2. Presence of cardiac atrial or ventricular lymphoma involvement.
3. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, New York Heart Association Class II or greater congestive heart failure, or other clinically significant cardiac disease within 12 months before enrolment.
4. Presence of primary immunodeficiency.
5. History of any medical condition including but not limited to autoimmune disease (eg, Crohn’s disease, rheumatoid arthritis, systemic lupus) requiring maintenance systemic immunosuppression/systemic disease modifying agents within the last 2 years. Endocrine conditions that require maintenance with physiologic dose steroids are allowed.
6. History of non-line associated, clinically significant (CTCAE 5.0 Grade 2 or greater) deep vein thrombosis or pulmonary embolism requiring therapeutic anticoagulation within 6 months of randomization.
7. Any medical condition or residual toxicities from prior therapies per investigator assessment likely to interfere with assessment of safety or efficacy of study treatment
8. History of severe immediate hypersensitivity reaction to any of the agents used in this study, including the lymphodepletion chemotherapy (cyclophosphamide or fludarabine).
9. Receipt of live vaccine ≤ 6 weeks before randomization and/or anticipation of need for such a vaccine during the subject’s participation in the study.
10. Females of childbearing potential who are pregnant or breastfeeding (due to potentially dangerous effects of the preparative chemotherapy on the fetus or infant).
11. Not willing to practice birth control from the time of consent through 12 months after the last dose of axicabtagene ciloleucel or SOCT.
12. The following WHO 2016 subcategories by local assessment: a) T-cell/histiocyte-rich LBCL b) Primary DLBCL of the 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
13. In the investigator’s judgment, the subject is unlikely to complete all study-specific visits or procedures, including follow-up visits, or comply with the study requirements for participation
14. History of severe immediate hypersensitivity reaction attributed to aminoglycosides
15. 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 active treatment. Discussion with the Kite medical monitor is encouraged.
16. History of acute or chronic active hepatitis B or C infection. If there is a positive history of treated hepatitis B or hepatitis C, the viral load must be undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing.
17. 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. Note: HIV-positive subjects in Australia are not permitted regardless of active anti-retroviral therapy or undetectable blood viral load (Refer to 12.4.4).
18. Presence of any indwelling line or drain (eg, percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter). Dedicated central venous access catheters, such as a Port-a-Cath or Hickman catheter, are permitted.
19. Presence of detectable cerebrospinal fluid (CSF)-malignant cells, brain metastases, or a history of central nervous system (CNS) involvement of lymphoma.
20. 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 enrollment.
21. 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
22. History of autologous or allogeneic stem cell transplant (SCT)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Event-free survival (EFS) by blinded central assessment.

Secondary endpoints 6

1. Progression-free survival (PFS) by blinded central assessment.
2. Overal survival (OS)
3. PFS by investigator assessment.
4. Complete remission (CR) rate by blinded central assessment.
5. Incidence of adverse events (AEs), serious adverse events (SAEs), deaths, and clinically significant changes in safety laboratory values
6. Patient-reported outcome (PRO)-QOL as measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire – Non-Hodgkin Lymphoma High Grade Module (EORTC QLQ-NHL-HG29), and European Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 6

Auxiliary 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Kite Pharma Inc.

Sponsor organisation

Kite Pharma Inc.

Address

2225 Colorado Avenue

City

Santa Monica

Postcode

90404-3505

Country

United States

Scientific contact point

Organisation

Kite Pharma Inc.

Contact name

EU CT Support

Public contact point

Organisation

Kite Pharma Inc.

Contact name

EU CT Support

Third parties 10

Locations

7 EU/EEA countries · 44 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 7 · Art. 38 CTR

Corrective measures 1 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 68 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

12 submissions — initial application plus substantial / non-substantial modifications