Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma, Large B-Cell, Diffuse

Lymphoma

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Pembrolizumab

Antibodies

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Immunoglobulins

Patient with relapsed or refractory DLBCL

Following preconditioning with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with doses from 50 x 10⁶ to 900 x 10⁶ CD19/ CD22 Chimeric Antigen Receptor (CAR) positive T cells followed by limited duration of anti-PD1 antibody (pembrolizumab).

AUTO3

The purpose of this study is to test the safety and efficacy of AUTO3, a CAR T cell treatment targeting CD19 and CD22 followed by limited duration of anti-PD1 antibody in patients with DLBCL

The study will consist of 2 phases, a Phase I or dose escalation and expansion phase, and a Phase II. Patients with relapsed or refractory DLBCL will be enrolled in both phases of the study. Eligible patients will undergo leukapheresis in order to harvest T cells, which is the starting material for the manufacture of the autologous CAR T product AUTO3 which is a CD19 and CD22 dual targeting CAR T cell product. Following pre-conditioning by a chemotherapeutic regimen, the patient will receive AUTO 3 intravenously as a single dose and in addition a limited duration of treatment with an anti-PD1 antibody (either as part of the pre-conditioning regimen or consolidation). Patients will then enter a 36-month follow-up period.

A dose escalation and expansion phase (Phase I) followed by Phase II

CD19/22 CAR T Cells (AUTO3) for the Treatment of Diffuse Large B Cell Lymphoma

A Single Arm, Open-label, Multi-centre, Phase I/II Study Evaluating the Safety and Clinical Activity of AUTO3, a CAR T Cell Treatment Targeting CD19 and CD22 With Anti PD1 Antibody in Patients With Relapsed or Refractory Diffuse Large B Cell Lymphoma

Autolus Limited

Atezolizumab

Axicabtagene ciloleucel

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Participants received conditioning chemotherapy consisting of 30 mg/m\^2 fludarabine and 500 mg/m\^2 cyclophosphamide intravenous (IV) infusion per day for 3 days followed by KTE-C19 IV infusion at a target dose of 2 x 10\^6 anti-CD19 chimeric antigen receptor (CAR) T cells/kg followed by 4 doses of atezolizumab (ATZ) (1200 mg/dose) IV infusion every 21 days, beginning 21 days following KTE-C19.

Participants received conditioning chemotherapy consisting of 30 mg/m\^2 fludarabine and 500 mg/m\^2 cyclophosphamide IV infusion per day for 3 days followed by KTE-C19 IV infusion at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg followed by 4 doses of ATZ (1200 mg/dose) IV infusion every 21 days, beginning 14 days following KTE-C19.

Participants received conditioning chemotherapy consisting of 30 mg/m\^2 fludarabine and 500 mg/m\^2 cyclophosphamide IV infusion per day for 3 days followed by KTE-C19 IV infusion at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg followed by 4 doses of ATZ (1200 mg/dose) IV infusion every 21 days, beginning 1 day following KTE-C19.

A single infusion of KTE-C19 CAR-T cells administered intravenously

KTE-C19

Kite Study Director

The primary objective of phase 1 is to evaluate the safety of KTE-C19 and atezolizumab combination regimens.

The primary objective of phase 2 is to evaluate the efficacy of KTE-C19 and atezolizumab, as measured by complete response rate in participants with refractory diffuse large B-cell lymphoma (DLBCL).

Participants who received an infusion of KTE-C19 will complete the remainder of the 15 year follow-up assessments in a separate long-term follow-up study, KT-US-982-5968 (NCT05041309).

This study uses a single group design. The arms reported in the Arms and Intervention section are based on the atezolizumab dosing schedule in the 4 Cohorts.

Study of Safety and Efficacy of KTE-C19 in Combination With Atezolizumab in Adults With Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

A Phase 1-2 Multi-Center Study Evaluating the Safety and Efficacy of KTE-C19 in Combination With Atezolizumab in Subjects With Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy

A DLT was defined as the following KTE-C19-related or ATZ-related events with an onset from immediately after the first ATZ infusion through 21 days after the first ATZ infusion: Grade 4 hematologic toxicity lasting \> 30 days (except lymphopenia or B-cell aplasia); All KTE-C19- or ATZ-related Grade 3 non-hematologic toxicities lasting for \> 7 days and all KTE-C19- or ATZ-related Grade 4 non-hematologic toxicities regardless of duration.

CRR was assessed based on the International Working Group Revised Response Criteria for Malignant Lymphoma (Cheson, 2007), and was defined as the percentage of participants achieving a complete response (CR) as assessed by the study investigators. CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease.

ORR was assessed based on the International Working Group Revised Response Criteria for Malignant Lymphoma (Cheson, 2007), and was defined as the percentage of participants achieving a CR or partial response (PR) as assessed by the study investigators. CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. PR was defined at least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses. Participants who did not meet the criteria for objective response by the analysis cutoff date were considered non-responders.

DOR for participants who experienced an objective response was defined as the date of their first confirmed objective response (CR or PR) to disease progression per the revised International Working Group Response Criteria for Malignant Lymphoma (Cheson, 2007) or death regardless of cause. CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. PR was defined at least a 50% decrease in SPD of up to six of the largest dominant nodes or nodal masses. Disease progression was defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir. The Kaplan-Meier approach was used to estimate DOR.

PFS was defined as the time from the KTE-C19 infusion date to the date of disease progression per the revised International Working Group Response Criteria for Malignant Lymphoma (Cheson, 2007) or death from any cause. Disease progression was defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir. The Kaplan-Meier approach was used to estimate PFS.

OS was defined as the time from KTE-C19 infusion to the date of death from any cause. The Kaplan-Meier approach was used to estimate OS.

An adverse event was defined as any untoward medical occurrence in a clinical trial participant. The event did not necessarily have a relationship with study treatment. Adverse events included worsening of a pre-existing medical condition. Worsening indicated that the pre-existing medical condition had increased in severity, frequency, and/or duration or had an association with a worse outcome. A pre-existing condition that had not worsened during the study or involved an intervention such as elective cosmetic surgery or a medical procedure while in study, was not considered an adverse event. TEAEs included all AEs with onset on or after initiation of axicabtagene ciloleucel.

Post axicabtagene ciloleucel infusion lab toxicities were reported. It included lab toxicities observed on or after the axicabtagene ciloleucel infusion date.

ALT = alanine aminotransferase; ALP = alkaline phosphatase; AST = aspartate aminotransferase.

Post axicabtagene ciloleucel infusion lab toxicities were reported. It included lab toxicities observed on or after the axicabtagene ciloleucel infusion date.

Genentech, Inc.

Kite, A Gilead Company

All-Cause Mortality: Participants from All Enrolled Analysis Set were included.

Serious Adverse Events and Other Adverse Events: The Safety Analysis Set was defined as all participants treated with any dose of KTE-C19.

Participants received conditioning chemotherapy consisting of 30 mg/m\^2 fludarabine and 500 mg/m\^2 cyclophosphamide IV infusion per day for 3 days followed by KTE-C19 IV infusion at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg followed by 4 doses of ATZ (1200 mg/dose) IV infusion every 21 days, beginning 21 days following KTE-C19.

Phase 1 Cohort 1: KTE-C19 + ATZ (21 Days After KTE-C19)

Phase 1 Cohort 2: KTE-C19 + ATZ (14 Days After KTE-C19)

Phase 1 Cohort 3: KTE-C19 + ATZ (1 Day After KTE-C19)

Phase 2: KTE-C19 + ATZ (1 Day After KTE-C19)

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

United States

Region of Enrollment

The Safety Analysis Set included all participants treated with any dose of KTE-C19.

Medical Information

DLT Evaluable Set included all participants in Phase 1 treated with KTE-C19 and at least 1 dose of ATZ who either received target KTE-C19 dose and followed for at least 21 days after first ATZ infusion; or received a dose of KTE-C19 lower than target for that cohort and a subsequent ATZ infusion and experienced a DLT.

Phase 1: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)

Phase 1 (Cohort 3) + Phase 2: KTE-C19 + ATZ

The Modified Intent-to-Treat Analysis (mITT) Set included all participants enrolled in Phase 1 Cohort 3 and Phase 2 and treated with target dose of KTE-C19 and at least one dose of atezolizumab.

Phase 1 and 2: Complete Response Rate (CRR)

Participants in the mITT Analysis Set were analyzed.

Phase 1 and 2: Objective Response Rate (ORR)

Participants in the mITT Analysis Set with objective response were analyzed.

Phase 1 and 2: Duration of Response (DOR)

Phase 1 and 2: Progression-Free Survival (PFS)

Phase 1 and 2: Overall Survival (OS)

The Safety Analysis Set was defined as all participants treated with any dose of KTE-C19.

Phase 1 and 2: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)

Shift to Grade 3 ALT

Shift to Grade 4 ALT

Shift to Grade 3 ALP

Shift to Grade 3 AST

Shift to Grade 4 AST

Shift to Grade 3 bilirubin

Shift to Grade 4 calcium

Shift to Grade 3 creatinine

Shift to Grade 4 creatinine

Shift to Grade 3 direct bilirubin

Shift to Grade 3 glucose

Shift to Grade 4 glucose

Participants in the Safety Analysis Set were analyzed.

Phase 1 and 2: Percentage of Participants With Serum Chemistry Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Values

Shift to Grade 3 albumin

Shift to Grade 3 calcium

Shift to Grade 3 phosphate

Shift to Grade 4 phosphate

Shift to Grade 3 potassium

Shift to Grade 3 sodium

Phase 1 and 2: Percentage of Participants With Serum Chemistry Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Values

Phase 1 and 2: Percentage of Participants With Hematology Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Values

Shift to Grade 3 hemoglobin

Shift to Grade 3 leukocytes

Shift to Grade 4 leukocytes

Shift to Grade 4 lymphocytes

Shift to Grade 3 neutrophils

Shift to Grade 4 neutrophils

Shift to Grade 3 platelets

Shift to Grade 4 platelets

Phase 1 and 2: Percentage of Participants With Hematology Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Values

Phase 1 and 2: Peak Anti-CD19 CAR T-Cell (KTE-C19) Level (Maximum Observed Plasma Concentration) in Blood

Phase 1 and 2: Percentage of Participants With Anti-KTE-C19 Antibodies

Day 1

Day 14

Day 21

Day 22

Day 35

Day 42

Day 43

Day 56

Day 63

Day 64

Day 77

Day 84

Day 154

Day 174

Participants in the Safety Analysis Set with available data were analyzed.

Phase 1 and 2: Atezolizumab Levels in Blood

Phase 1 and 2: Percentage of Participants With Anti-Atezolizumab Antibodies

Phase 1 and 2: Peak Serum Levels of C-Reactive Protein (CRP) in Blood

CXCL 10

IFN-γ

IL-1RA

IL-2

IL-6

IL-8

IL-15

TNF-α

Phase 1 and 2: Peak Serum Levels of C-X-C Motif Chemokine 10 (CXCL10), Interferon-Gamma (IFN-γ), Interleukin-1 Receptor Antagonist (IL-1RA), Interleukin (IL)-2, IL-6, IL-8, IL-15, and Tumor Necrosis Factor-Alpha (TNF-α) in Blood

Phase 1 and 2: Peak Serum Levels of Ferritin in Blood

Phase 1 and 2: Peak Serum Levels of Interleukin-2 Receptor Alpha (IL-2Rα) in Blood

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
CD19/22 CAR T Cells (AUTO3) for the Treatment of Diffuse Large B Cell Lymphoma	NCT03287817	Diffuse Large B... Relapsed Diffus... Refractory Diff... DLBCL	AUTO3	18 Years -	Autolus Limited
Study of Safety and Efficacy of KTE-C19 in Combination With Atezolizumab in Adults With Refractory Diffuse Large B-Cell Lymphoma (DLBCL)	NCT02926833	Refractory Diff...	KTE-C19 Atezolizumab Cyclophosphamid... Fludarabine	18 Years -	Gilead Sciences
Study of Safety and Efficacy of KTE-C19 in Combination With Atezolizumab in Adults With Refractory Diffuse Large B-Cell Lymphoma (DLBCL)	NCT02926833	Refractory Diff...	KTE-C19 Atezolizumab Cyclophosphamid... Fludarabine	18 Years -	Gilead Sciences

Spots Global Cancer Trial Database for refractory diffuse large b cell lymphoma