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

PHASE3RECRUITING

The goal of this clinical study is to compare the study drug, axicabtagene ciloleucel, versus standard of care (SOC) in first-line therapy in participants with high-risk large B-cell lymphoma.

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Study details:

Five years after randomization, participants who have received axicabtagene ciloleucel will transition to a separate long-term follow-up study (study KT-US-982-5968) to complete the remainder of the 15-year follow-up assessments.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

Histologically confirmed large B cell lymphoma (LBCL) based on 2016 World Health Organization (WHO) classification by local pathology lab assessment, including of the following:

Diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS)

High-grade B-cell lymphoma (HGBL)

Note: Transformed DLBCL from follicular lymphoma or from marginal zone lymphoma is eligible if no prior treatment with anthracycline-containing regimen.

High-risk disease defined as an International Prognostic Index (IPI) score of 4 or 5 at initial diagnosis.

Have received only 1 cycle of rituximab plus chemotherapy (R-chemotherapy).

Adequate bone marrow, renal, hepatic, pulmonary, and cardiac function.

Females of childbearing potential must have a negative serum or urine pregnancy test.

Exclusion criteria

The following WHO 2016 subcategories by local assessment:

T-cell/histiocyte-rich LBCL

Primary DLBCL of the central nervous system (CNS)

Primary mediastinal (thymic) LBCL

B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma

Burkitt lymphoma

History of Richter's transformation of chronic lymphocytic leukemia

Presence of detectable cerebrospinal fluid (CSF)-malignant cells, brain metastases, or a history of CNS involvement of lymphoma.

Presence of cardiac lymphoma involvement.

Any prior treatment for LBCL other than the 1 cycle of R-chemotherapy.

History of severe immediate hypersensitivity reaction to any of the agents used in this study.

Presence of CNS disorder. History of stroke, transient ischemic attack, or posterior reversible encephalopathy syndrome (PRES) within 12 months prior to enrollment.

History of acute or chronic active hepatitis B or C infection.

Positive for human immunodeficiency virus (HIV) unless taking appropriate anti-HIV medications, with an undetectable viral load by PCR and with a cluster of differentiation 4 (CD4) count > 200 cells/uL.

Medical conditions or residual toxicities from prior therapies likely to interfere with assessment of safety or efficacy of study treatment. Please refer to protocol for further details.

History of clinically significant cardiac disease within 12 months before enrollment.

History of any medical condition requiring maintenance systemic immunosuppression/systemic disease modifying agents within the last 2 years.

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2023-02-10

Primary completion: 2031-03-01

Study completion finish: 2031-03-01

Study type

TREATMENT

Phase

PHASE3

Trial ID

NCT05605899

Intervention or treatment

BIOLOGICAL: Axicabtagene Ciloleucel

DRUG: Cyclophosphamide

DRUG: Fludarabine

DRUG: Etoposide

DRUG: Rituximab

DRUG: Doxorubicin

DRUG: Vincristine

DRUG: Prednisone

Conditions

• High-risk Large B-cell Lymphoma (LBCL)

Image related to High-risk Large B-cell Lymphoma (LBCL)

Condition: High-risk Large B-cell Lymphoma (LBCL)
BIOLOGICAL: Axicabtagene Ciloleucel and other drugs
Camperdown, New South Wales, Australia and more
Sponsor: Kite, A Gilead Company

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

Are you running this trial? If you're a clinic or sponsor, you can claim this study. Claim or learn more.

Find a site

Closest Location:

Royal Prince Alfred Hospital

Research sites nearby

Select from list below to view details:

Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia
Peter MacCallum Cancer Center
Melbourne, Victoria, Australia
Royal Brisbane and Women's Hospital
South Brisbane, Queensland, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Axicabtagene Ciloleucel Participants will receive cyclophosphamide 500 mg/m\^2/day intravenously (IV) and fludarabine 30 mg/m\^2/day IV lymphodepletion chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10\^6 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) transduced autologous T cells/kg on Day 0.	BIOLOGICAL: Axicabtagene Ciloleucel A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells
ACTIVE_COMPARATOR: Standard of Care Therapy Participants will receive the investigator's choice of one of the following therapies/dosing schedules: * Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for a total of 6 cycles (21-day cycle) * Rituximab 375 mg/m\^2 on Day 1 * Cyclophosphamide 750 mg/m\^2 on Day 1 * Doxorubicin 50 mg/m\^2 on Day 1 * Vincristine 1.4 mg/m\^2 (maximum 2 mg) on Day 1 * Prednisone 40 mg/m\^2 on Day 1 through Day 5 * Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) for a total of 6 cycles (21-day cycle) * Rituximab 375 mg/m\^2 on Day 1 * Etoposide 50 mg/m\^2 on Days 1 to 4 * Doxorubicin 10 mg/m\^2 on Days 1 to 4 * Vincristine 0.4 mg/m\^2 on Days 1 to 4 * Cyclophosphamide 750 mg/m\^2 on Day 5 * Prednisone 60 mg/m\^2 twice daily on Days 1 to 5	DRUG: Cyclophosphamide Administered intravenously

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Axicabtagene Ciloleucel

Participants will receive cyclophosphamide 500 mg/m\^2/day intravenously (IV) and fludarabine 30 mg/m\^2/day IV lymphodepletion chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10\^6 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) transduced autologous T cells/kg on Day 0.

BIOLOGICAL: Axicabtagene Ciloleucel

A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells

ACTIVE_COMPARATOR: Standard of Care Therapy

Participants will receive the investigator's choice of one of the following therapies/dosing schedules:
* Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for a total of 6 cycles (21-day cycle)
* Rituximab 375 mg/m\^2 on Day 1
* Cyclophosphamide 750 mg/m\^2 on Day 1
* Doxorubicin 50 mg/m\^2 on Day 1
* Vincristine 1.4 mg/m\^2 (maximum 2 mg) on Day 1
* Prednisone 40 mg/m\^2 on Day 1 through Day 5
* Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) for a total of 6 cycles (21-day cycle)
* Rituximab 375 mg/m\^2 on Day 1
* Etoposide 50 mg/m\^2 on Days 1 to 4
* Doxorubicin 10 mg/m\^2 on Days 1 to 4
* Vincristine 0.4 mg/m\^2 on Days 1 to 4
* Cyclophosphamide 750 mg/m\^2 on Day 5
* Prednisone 60 mg/m\^2 twice daily on Days 1 to 5

DRUG: Cyclophosphamide

Administered intravenously

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
Event-free Survival (EFS) by Blinded Central Assessment	EFS, is defined as the time from randomization to the earliest occurrence of death due to any cause, disease progression/relapse, initiation of any non-protocol specified subsequent new lymphoma therapy for the treatment of residual disease or Biopsy-proven residual disease at the Month 6 disease assessment or later, regardless of whether subsequent new lymphoma therapy is initiated or not.	Up to 5 years

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Progression-free Survival (PFS) by Blinded Central Assessment	PFS is defined as the time from randomization to disease progression or death due to any cause.	Up to 5 years
Overall Survival	OS is defined as the time from randomization to death due to any cause.	Up to 5 years
PFS by Investigator Assessment	PFS is defined as the time from randomization to disease progression or death due to any cause.	Up to 5 years
Complete Response (CR) Rate by Blinded Central Assessment	CR rate is defined as the proportion of participants who have achieved CR per Lugano classification after treatment completion and prior to subsequent new off protocol anti-lymphoma therapy.	Up to 5 years
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	Not Specified	First dose date up to 5 years plus 30 days
Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values	Not Specified	First dose date up to 5 years plus 30 days
Change From Baseline in the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire-30 (EORTC QLQ-C30) Score	The EORTC-QLQ-C30 is a multi-item questionnaire measuring the following content: five (5) multi-item functional scales, three (3) multi-item symptom scales, six (6) symptom single-item scales, one (1) global health status scale, and one (1) global health-related quality of life (HRQoL). Each scale is measured from 0 to 100 after a linear transformation. Higher scores for functioning scales and for the Global Health Status or Global HRQoL scales indicate a higher level of functioning and a better HRQoL respectively, whereas higher scores in symptom scales represent a higher level of symptoms.	Baseline, Month 18
Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Non-Hodgkin Lymphoma High Grade Module (EORTC QLQ-NHL-HG29) Score	The EORTC QLQ-NHL-HG29 is a 29-item patient-reported assessment measuring patients' high-grade NHL-specific symptoms and functioning. The 29 items assess symptom burden due to disease and/or treatment, fatigue/physical condition, neuropathy, emotional impacts, and worries/fears health and functioning. Each scale is measured from 0 to 100 after a linear transformation. Higher scores for functional scales indicate a higher level of functioning and a better HRQoL, whereas higher scores in symptom scales represent a higher level of symptoms.	Baseline, Month 18
Change From Baseline in the European Quality of Life Five Dimensions Five Levels Questionnaire (EQ-5D-5L) Score	The EQ-5D-5L questionnaire is a generic measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L comprises 2 components: a questionnaire covering 5 dimensions and a tariff of values based upon direct valuations of health states using a visual analog scale (VAS). Rating gets recorded on a vertical VAS in which the endpoints are labeled best imaginable health state is 100 (on the top) and worst imaginable health state is 0 (on the bottom). Higher scores of EQ VAS indicate better health.	Baseline, Month 18

Frequently Asked Questions

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References

Clinical Trials Gov: Study to Compare Axicabtagene Ciloleucel With Standard of Care Therapy as First-line Treatment in Participants With High-risk Large B-cell Lymphoma