ZUMA-6: Safety and Efficacy of KTE-C19 in Combination With Atezolizumab in Adults With Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Sponsor
Kite, A Gilead Company (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02926833
Collaborator
Genentech, Inc. (Industry)
37
5
1
71.1
7.4
0.1
Study Details
Study Description
Brief Summary
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).
Subjects 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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
37 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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)
Actual Study Start Date
:
Sep 29, 2016
Actual Primary Completion Date
:
Feb 21, 2019
Anticipated Study Completion Date
:
Sep 1, 2022
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: KTE-C19 + ATZ Participants will receive 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. Treatment with ATZ will begin 21 days following KTE-C19 (Phase 1 Cohort 1), 14 days following KTE-C19 (Phase 1 Cohort 2), and 1 day following KTE-C19 (Phase 1, Cohort 3 & Phase 2). |
Biological: KTE-C19
A single infusion of KTE-C19 CAR-T cells administered intravenously
Other Names:
Biological: Atezolizumab
Administered intravenously
Drug: Cyclophosphamide
Administered intravenously
Drug: Fludarabine
Administered intravenously
|
Outcome Measures
Primary Outcome Measures
- Phase 1: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) [Baseline up to 21 days]
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.
- Phase 1 and 2: Complete Response Rate (CRR) [Month 6]
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.
Secondary Outcome Measures
- Phase 1 and 2: Objective Response Rate (ORR) [From enrollment until first occurrence of CR or PR (up to approximately 2.5 years)]
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.
- Phase 1 and 2: Duration of Response (DOR) [From the date of first confirmed objective response (CR or PR) to disease progression or death regardless of cause (up to approximately 2.5 years)]
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.
- Phase 1 and 2: Progression-Free Survival (PFS) [From the date of first KTE-C19 infusion to disease progression or death regardless of cause (up to approximately 2.5 years )]
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.
- Phase 1 and 2: Overall Survival (OS) [From the date of first KTE-C19 infusion to the date of death regardless of cause (up to approximately 2.5 years)]
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.
- Phase 1 and 2: Percentage of Participants Experiencing Adverse Events (AEs) [Enrollment up to 30 days after completion of the final dose of atezolizumab, or 3 months after the KTE-C19 infusion, whichever was longer (up to approximately 2.5 years)]
- Phase 1 and 2: Percentage of Participants With Serum Chemistry Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Values [Enrollment up to 30 days after completion of the final dose of atezolizumab, or 3 months after the KTE-C19 infusion, whichever was longer (up to approximately 2.5 years)]
ALT = alanine aminotransferase; ALP = alkaline phosphatase; AST = aspartate aminotransferase.
- Phase 1 and 2: Percentage of Participants With Serum Chemistry Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Values [Enrollment up to 30 days after completion of the final dose of atezolizumab, or 3 months after the KTE-C19 infusion, whichever was longer (up to approximately 2.5 years)]
- Phase 1 and 2: Percentage of Participants With Hematology Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Values [Enrollment up to 30 days after completion of the final dose of atezolizumab, or 3 months after the KTE-C19 infusion, whichever was longer (up to approximately 2.5 years)]
- Phase 1 and 2: Percentage of Participants With Hematology Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Values [Enrollment up to 30 days after completion of the final dose of atezolizumab, or 3 months after the KTE-C19 infusion, whichever was longer (up to approximately 2.5 years)]
- Phase 1 and 2: Peak Anti-CD19 CAR T-Cell (KTE-C19) Level (Maximum Observed Plasma Concentration) in Blood [Pre-infusion (Baseline); Post-infusion: Days 7 (Phase 2), 14, 22 (Phase 2), 28 (Phase 2; optional), 35 (Phase 1, Cohort 3; optional), 43, 49 (optional), 64, 69 (optional), 94; long-term follow-up: every 3 months from Month 6 to Month 18, and Month 24]
- Phase 1 and 2: Percentage of Participants With Anti-KTE-C19 Antibodies [Baseline up to approximately 2.5 years]
- Phase 1 and 2: Atezolizumab Levels in Blood [Days 1, 14, 21, 22, 35, 42, 43, 56, 63, 64, 77, 84, 154, and 174]
- Phase 1 and 2: Percentage of Participants With Anti-Atezolizumab Antibodies [Baseline up to approximately 2.5 years]
- Phase 1 and 2: Peak Serum Levels of C-Reactive Protein (CRP) in Blood [Baseline (pre-conditioning chemotherapy); Day 0 (pre-KTE-C19 infusion); Days 1, 4, 7, and 14, and 22 , optional Day 28 (Phase 2) or Day 35 (Phase 1 Cohort 3), optional Day 49, optional Day 69, and Day 94 post-KTE-C19 infusion]
- 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 [Baseline (pre-conditioning chemotherapy); Day 0 (pre-KTE-C19 infusion); Days 1, 4, 7, and 14, and 22 , optional Day 28 (Phase 2) or Day 35 (Phase 1 Cohort 3), optional Day 49, optional Day 69, and Day 94 post-KTE-C19 infusion]
- Phase 1 and 2: Peak Serum Levels of Ferritin in Blood [Baseline (pre-conditioning chemotherapy); Day 0 (pre-KTE-C19 infusion); Days 1, 4, 7, and 14, and 22 , optional Day 28 (Phase 2) or Day 35 (Phase 1 Cohort 3), optional Day 49, optional Day 69, and Day 94 post-KTE-C19 infusion]
- Phase 1 and 2: Peak Serum Levels of Interleukin-2 Receptor Alpha (IL-2Rα) in Blood [Baseline (pre-conditioning chemotherapy); Day 0 (pre-KTE-C19 infusion); Days 1, 4, 7, and 14, and 22 , optional Day 28 (Phase 2) or Day 35 (Phase 1 Cohort 3), optional Day 49, optional Day 69, and Day 94 post-KTE-C19 infusion]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Key Inclusion Criteria:
-
Histologically confirmed DLBCL
-
Chemotherapy-refractory disease, defined as one or more of the following:
-
Stable disease (duration of stable disease must be less than or equal to 6 months) or progressive disease as best response to most recent chemotherapy containing regimen
-
Disease progression or recurrence less than or equal to 12 months of prior autologous stem cell transplantation (SCT)
- Individuals must have received adequate prior therapy including at a minimum:
-
anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20-negative; and
-
an anthracycline containing chemotherapy regimen
-
At least one measurable lesion per revised International Working Group (IWG) Response Criteria
-
Age 18 years or older
-
Eastern cooperative oncology group (ECOG) performance status of 0 or 1
-
Adequate organ and bone marrow function
-
All individuals or legally appointed representatives/caregivers, must personally sign and date the institutional review board (IRB)/independent ethics committee (IEC) approved consent form before initiating any study specific procedures or activities.
Key Exclusion Criteria:
-
History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, breast) or follicular lymphoma unless disease free for at least 3 years
-
History of allogeneic stem cell transplantation
-
Prior CAR therapy or other genetically modified T cell therapy
-
Clinically significant active infection
-
Known history of infection with HIV or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive)
-
Individuals with detectable cerebrospinal fluid malignant cells or brain metastases or with a history of cerebrospinal fluid malignant cells or brain metastases
-
History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with central nervous system (CNS) involvement
-
History of autoimmune disease. Participants with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone and participants with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible for this study.
-
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.
-
Prior treatment with PD-L1 inhibitor, PD-1 inhibitor, anti-CTLA4, anti-CD137, anti-OX40 or other immune checkpoint blockade or activator therapy with the exception of Individuals who received atezolizumab in this study and are eligible for re-treatment
-
Prior CD19 targeted therapy
Note: Other protocol defined Inclusion/Exclusion criteria may apply
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | City of Hope | Duarte | California | United States | 91010 |
| 2 | Stanford Cancer Center | Palo Alto | California | United States | 94305 |
| 3 | H Lee Moffitt Cancer Center | Tampa | Florida | United States | 33612 |
| 4 | Dana Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
| 5 | University of Texas MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- Kite, A Gilead Company
- Genentech, Inc.
Investigators
- Study Director: Kite Study Director, Kite, A Gilead Company
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Kite, A Gilead Company
ClinicalTrials.gov Identifier:
NCT02926833
Other Study ID Numbers:
- KTE-C19-106
First Posted:
Oct 6, 2016
Last Update Posted:
May 23, 2022
Last Verified:
Apr 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants were enrolled at study sites in United States. The first participant was screened on 29 September 2016. The last study visit for the primary endpoint occurred on 21 February 2019. |
|---|---|
| Pre-assignment Detail | 44 participants were screened. |
| Arm/Group Title | 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) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. |
| Period Title: Overall Study | ||||
| STARTED | 3 | 4 | 7 | 23 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 3 | 4 | 7 | 23 |
Baseline Characteristics
| Arm/Group Title | 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 |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | Total of all reporting groups |
| Overall Participants | 3 | 3 | 6 | 22 | 34 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
56.0
(14.80)
|
42.7
(19.50)
|
53.2
(6.18)
|
58.4
(7.40)
|
55.9
(9.92)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
0
0%
|
2
66.7%
|
4
66.7%
|
8
36.4%
|
14
41.2%
|
| Male |
3
100%
|
1
33.3%
|
2
33.3%
|
14
63.6%
|
20
58.8%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
1
33.3%
|
1
33.3%
|
0
0%
|
1
4.5%
|
3
8.8%
|
| Not Hispanic or Latino |
2
66.7%
|
2
66.7%
|
6
100%
|
20
90.9%
|
30
88.2%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
1
4.5%
|
1
2.9%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||
| Asian |
1
33.3%
|
0
0%
|
1
16.7%
|
3
13.6%
|
5
14.7%
|
| White |
2
66.7%
|
3
100%
|
5
83.3%
|
18
81.8%
|
28
82.4%
|
| Other |
0
0%
|
0
0%
|
0
0%
|
1
4.5%
|
1
2.9%
|
Outcome Measures
| Title | Phase 1: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) |
|---|---|
| Description | 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. |
| Time Frame | Baseline up to 21 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | 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) |
|---|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 3 | 3 | 6 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
1
16.7%
|
| Title | Phase 1 and 2: Complete Response Rate (CRR) |
|---|---|
| Description | 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. |
| Time Frame | Month 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Phase 1 (Cohort 3) + Phase 2: KTE-C19 + ATZ |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 28 |
| Number (95% Confidence Interval) [percentage of participants] |
46
1533.3%
|
| Title | Phase 1 and 2: Objective Response Rate (ORR) |
|---|---|
| Description | 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. |
| Time Frame | From enrollment until first occurrence of CR or PR (up to approximately 2.5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the mITT Analysis Set were analyzed. |
| Arm/Group Title | Phase 1 (Cohort 3) + Phase 2: KTE-C19 + ATZ |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 28 |
| Number (95% Confidence Interval) [percentage of participants] |
75
2500%
|
| Title | Phase 1 and 2: Duration of Response (DOR) |
|---|---|
| Description | 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. |
| Time Frame | From the date of first confirmed objective response (CR or PR) to disease progression or death regardless of cause (up to approximately 2.5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the mITT Analysis Set with objective response were analyzed. |
| Arm/Group Title | Phase 1 (Cohort 3) + Phase 2: KTE-C19 + ATZ |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 21 |
| Median (95% Confidence Interval) [months] |
NA
|
| Title | Phase 1 and 2: Progression-Free Survival (PFS) |
|---|---|
| Description | 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. |
| Time Frame | From the date of first KTE-C19 infusion to disease progression or death regardless of cause (up to approximately 2.5 years ) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the mITT Analysis Set were analyzed. |
| Arm/Group Title | Phase 1 (Cohort 3) + Phase 2: KTE-C19 + ATZ |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 28 |
| Median (95% Confidence Interval) [months] |
NA
|
| Title | Phase 1 and 2: Overall Survival (OS) |
|---|---|
| Description | 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. |
| Time Frame | From the date of first KTE-C19 infusion to the date of death regardless of cause (up to approximately 2.5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the mITT Analysis Set were analyzed. |
| Arm/Group Title | Phase 1 (Cohort 3) + Phase 2: KTE-C19 + ATZ |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 28 |
| Median (95% Confidence Interval) [months] |
NA
|
| Title | Phase 1 and 2: Percentage of Participants Experiencing Adverse Events (AEs) |
|---|---|
| Description | |
| Time Frame | Enrollment up to 30 days after completion of the final dose of atezolizumab, or 3 months after the KTE-C19 infusion, whichever was longer (up to approximately 2.5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Analysis Set was defined as all participants treated with any dose of KTE-C19. |
| Arm/Group Title | 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) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 3 | 3 | 6 | 22 |
| Number [percentage of participants] |
100
3333.3%
|
100
3333.3%
|
100
1666.7%
|
100
454.5%
|
| Title | Phase 1 and 2: Percentage of Participants With Serum Chemistry Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Values |
|---|---|
| Description | ALT = alanine aminotransferase; ALP = alkaline phosphatase; AST = aspartate aminotransferase. |
| Time Frame | Enrollment up to 30 days after completion of the final dose of atezolizumab, or 3 months after the KTE-C19 infusion, whichever was longer (up to approximately 2.5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set were analyzed. |
| Arm/Group Title | 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) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 3 | 3 | 6 | 22 |
| Shift to Grade 3 ALT |
0
0%
|
0
0%
|
0
0%
|
5
22.7%
|
| Shift to Grade 4 ALT |
0
0%
|
0
0%
|
0
0%
|
5
22.7%
|
| Shift to Grade 3 ALP |
0
0%
|
0
0%
|
0
0%
|
14
63.6%
|
| Shift to Grade 3 AST |
0
0%
|
0
0%
|
0
0%
|
9
40.9%
|
| Shift to Grade 4 AST |
0
0%
|
0
0%
|
0
0%
|
5
22.7%
|
| Shift to Grade 3 bilirubin |
0
0%
|
0
0%
|
0
0%
|
9
40.9%
|
| Shift to Grade 4 calcium |
0
0%
|
0
0%
|
0
0%
|
5
22.7%
|
| Shift to Grade 3 creatinine |
0
0%
|
0
0%
|
0
0%
|
9
40.9%
|
| Shift to Grade 4 creatinine |
0
0%
|
0
0%
|
0
0%
|
5
22.7%
|
| Shift to Grade 3 direct bilirubin |
33
1100%
|
33
1100%
|
17
283.3%
|
14
63.6%
|
| Shift to Grade 3 glucose |
0
0%
|
0
0%
|
0
0%
|
18
81.8%
|
| Shift to Grade 4 glucose |
0
0%
|
0
0%
|
0
0%
|
14
63.6%
|
| Title | Phase 1 and 2: Percentage of Participants With Serum Chemistry Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Values |
|---|---|
| Description | |
| Time Frame | Enrollment up to 30 days after completion of the final dose of atezolizumab, or 3 months after the KTE-C19 infusion, whichever was longer (up to approximately 2.5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set were analyzed. |
| Arm/Group Title | 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) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 3 | 3 | 6 | 22 |
| Shift to Grade 3 albumin |
33
1100%
|
0
0%
|
0
0%
|
9
40.9%
|
| Shift to Grade 3 calcium |
33
1100%
|
0
0%
|
0
0%
|
5
22.7%
|
| Shift to Grade 4 calcium |
0
0%
|
0
0%
|
0
0%
|
18
81.8%
|
| Shift to Grade 3 phosphate |
67
2233.3%
|
67
2233.3%
|
33
550%
|
36
163.6%
|
| Shift to Grade 4 phosphate |
0
0%
|
0
0%
|
0
0%
|
36
163.6%
|
| Shift to Grade 3 potassium |
0
0%
|
0
0%
|
0
0%
|
14
63.6%
|
| Shift to Grade 3 sodium |
67
2233.3%
|
0
0%
|
17
283.3%
|
14
63.6%
|
| Shift to Grade 4 glucose |
0
0%
|
0
0%
|
17
283.3%
|
0
0%
|
| Title | Phase 1 and 2: Percentage of Participants With Hematology Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Values |
|---|---|
| Description | |
| Time Frame | Enrollment up to 30 days after completion of the final dose of atezolizumab, or 3 months after the KTE-C19 infusion, whichever was longer (up to approximately 2.5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set were analyzed. |
| Arm/Group Title | 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) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 3 | 3 | 6 | 22 |
| Number [percentage of participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Phase 1 and 2: Percentage of Participants With Hematology Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Values |
|---|---|
| Description | |
| Time Frame | Enrollment up to 30 days after completion of the final dose of atezolizumab, or 3 months after the KTE-C19 infusion, whichever was longer (up to approximately 2.5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set were analyzed. |
| Arm/Group Title | 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) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 3 | 3 | 6 | 22 |
| Shift to Grade 3 hemoglobin |
100
3333.3%
|
67
2233.3%
|
83
1383.3%
|
59
268.2%
|
| Shift to Grade 3 leukocytes |
0
0%
|
0
0%
|
33
550%
|
18
81.8%
|
| Shift to Grade 4 leukocytes |
100
3333.3%
|
100
3333.3%
|
67
1116.7%
|
77
350%
|
| Shift to Grade 4 lymphocytes |
100
3333.3%
|
100
3333.3%
|
100
1666.7%
|
86
390.9%
|
| Shift to Grade 3 neutrophils |
0
0%
|
33
1100%
|
17
283.3%
|
14
63.6%
|
| Shift to Grade 4 neutrophils |
100
3333.3%
|
67
2233.3%
|
83
1383.3%
|
73
331.8%
|
| Shift to Grade 3 platelets |
33
1100%
|
0
0%
|
17
283.3%
|
18
81.8%
|
| Shift to Grade 4 platelets |
33
1100%
|
67
2233.3%
|
17
283.3%
|
32
145.5%
|
| Title | Phase 1 and 2: Peak Anti-CD19 CAR T-Cell (KTE-C19) Level (Maximum Observed Plasma Concentration) in Blood |
|---|---|
| Description | |
| Time Frame | Pre-infusion (Baseline); Post-infusion: Days 7 (Phase 2), 14, 22 (Phase 2), 28 (Phase 2; optional), 35 (Phase 1, Cohort 3; optional), 43, 49 (optional), 64, 69 (optional), 94; long-term follow-up: every 3 months from Month 6 to Month 18, and Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set were analyzed. |
| Arm/Group Title | 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) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 3 | 3 | 6 | 22 |
| Mean (Standard Deviation) [cells/μL] |
86.87
(67.17)
|
167.88
(91.58)
|
60.71
(70.66)
|
60.22
(60.24)
|
| Title | Phase 1 and 2: Percentage of Participants With Anti-KTE-C19 Antibodies |
|---|---|
| Description | |
| Time Frame | Baseline up to approximately 2.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set were analyzed. |
| Arm/Group Title | 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) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 3 | 3 | 6 | 22 |
| Number [percentage of participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Phase 1 and 2: Atezolizumab Levels in Blood |
|---|---|
| Description | |
| Time Frame | Days 1, 14, 21, 22, 35, 42, 43, 56, 63, 64, 77, 84, 154, and 174 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with available data were analyzed. |
| Arm/Group Title | 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) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 3 | 3 | 6 | 22 |
| Day 1 |
373000
(65300)
|
323000
(89300)
|
||
| Day 14 |
435000
(61500)
|
|||
| Day 21 |
403000
(46100)
|
|||
| Day 22 |
73900
(27900)
|
110000
(126000)
|
||
| Day 35 |
84200
(14300)
|
|||
| Day 42 |
98800
(16500)
|
|||
| Day 43 |
138000
(78700)
|
136000
(69900)
|
||
| Day 56 |
176000
(2828.43)
|
|||
| Day 63 |
175000
(7505.55)
|
|||
| Day 64 |
159000
(91600)
|
199000
(76000)
|
||
| Day 77 |
240000
(33000)
|
|||
| Day 84 |
209000
(24800)
|
|||
| Day 154 |
66800
(58900)
|
|||
| Day 174 |
91000
|
| Title | Phase 1 and 2: Percentage of Participants With Anti-Atezolizumab Antibodies |
|---|---|
| Description | |
| Time Frame | Baseline up to approximately 2.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set were analyzed. |
| Arm/Group Title | 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) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 3 | 3 | 6 | 22 |
| Number [percentage of participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Phase 1 and 2: Peak Serum Levels of C-Reactive Protein (CRP) in Blood |
|---|---|
| Description | |
| Time Frame | Baseline (pre-conditioning chemotherapy); Day 0 (pre-KTE-C19 infusion); Days 1, 4, 7, and 14, and 22 , optional Day 28 (Phase 2) or Day 35 (Phase 1 Cohort 3), optional Day 49, optional Day 69, and Day 94 post-KTE-C19 infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the mITT Analysis Set were analyzed. |
| Arm/Group Title | Phase 1 (Cohort 3) + Phase 2: KTE-C19 + ATZ |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 28 |
| Median (Full Range) [mg/L] |
174.03
|
| Title | 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 |
|---|---|
| Description | |
| Time Frame | Baseline (pre-conditioning chemotherapy); Day 0 (pre-KTE-C19 infusion); Days 1, 4, 7, and 14, and 22 , optional Day 28 (Phase 2) or Day 35 (Phase 1 Cohort 3), optional Day 49, optional Day 69, and Day 94 post-KTE-C19 infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the mITT Analysis Set were analyzed. |
| Arm/Group Title | Phase 1 (Cohort 3) + Phase 2: KTE-C19 + ATZ |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 28 |
| CXCL 10 |
2000.00
|
| IFN-γ |
587.80
|
| IL-1RA |
2801.20
|
| IL-2 |
17.55
|
| IL-6 |
121.55
|
| IL-8 |
180.65
|
| IL-15 |
48.95
|
| TNF-α |
8.20
|
| Title | Phase 1 and 2: Peak Serum Levels of Ferritin in Blood |
|---|---|
| Description | |
| Time Frame | Baseline (pre-conditioning chemotherapy); Day 0 (pre-KTE-C19 infusion); Days 1, 4, 7, and 14, and 22 , optional Day 28 (Phase 2) or Day 35 (Phase 1 Cohort 3), optional Day 49, optional Day 69, and Day 94 post-KTE-C19 infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the mITT Analysis Set were analyzed. |
| Arm/Group Title | Phase 1 (Cohort 3) + Phase 2: KTE-C19 + ATZ |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 28 |
| Median (Full Range) [μg/mL] |
1.54
|
| Title | Phase 1 and 2: Peak Serum Levels of Interleukin-2 Receptor Alpha (IL-2Rα) in Blood |
|---|---|
| Description | |
| Time Frame | Baseline (pre-conditioning chemotherapy); Day 0 (pre-KTE-C19 infusion); Days 1, 4, 7, and 14, and 22 , optional Day 28 (Phase 2) or Day 35 (Phase 1 Cohort 3), optional Day 49, optional Day 69, and Day 94 post-KTE-C19 infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the mITT Analysis Set were analyzed. |
| Arm/Group Title | Phase 1 (Cohort 3) + Phase 2: KTE-C19 + ATZ |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 28 |
| Median (Full Range) [ng/mL] |
17.25
|
Adverse Events
| Time Frame | Enrollment up to 30 days after completion of the final dose of atezolizumab, or 3 months after the KTE-C19 infusion, whichever was longer (up to approximately 2.5 years) | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | All-Cause Mortality: The Full Analysis Set included all enrolled participants. Serious Adverse Events and Other Adverse Events: The Safety Analysis Set was defined as all participants treated with any dose of KTE-C19. One participant in Phase 2 arm who has the reason of 'not completed' mentioned as 'full consent withdrawal' in the Participant Flow section, actually died, hence that participant was counted here in All-Cause Mortality. | |||||||
| Arm/Group Title | 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) | ||||
| Arm/Group Description | 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. | 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. | 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. | ||||
All Cause Mortality |
||||||||
| 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) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/3 (33.3%) | 1/4 (25%) | 1/7 (14.3%) | 8/23 (34.8%) | ||||
Serious Adverse Events |
||||||||
| 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) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 2/3 (66.7%) | 3/6 (50%) | 15/22 (68.2%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/3 (0%) | 1/3 (33.3%) | 1/6 (16.7%) | 0/22 (0%) | ||||
| Febrile neutropenia | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Neutropenia | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/22 (0%) | ||||
| Cardiac disorders | ||||||||
| Supraventricular tachycardia | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Diarrhoea | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Gastrointestinal haemorrhage | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/22 (0%) | ||||
| Jejunal perforation | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/22 (0%) | ||||
| Nausea | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Obstruction gastric | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/22 (0%) | ||||
| Vomiting | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| General disorders | ||||||||
| Localised oedema | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Multiple organ dysfunction syndrome | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Pain | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Pyrexia | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 3/22 (13.6%) | ||||
| Immune system disorders | ||||||||
| Haemophagocytic lymphohistiocytosis | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Infections and infestations | ||||||||
| Encephalitis | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Lung infection | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 0/22 (0%) | ||||
| Pneumonia | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Pneumonia cytomegaloviral | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Pneumonia staphylococcal | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Pseudomonas infection | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Sepsis | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Sinusitis | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Staphylococcal infection | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 2/22 (9.1%) | ||||
| Upper respiratory tract infection | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Urinary tract infection | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 2/22 (9.1%) | ||||
| Investigations | ||||||||
| Aspartate aminotransferase increased | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/22 (0%) | ||||
| Neutrophil count decreased | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/22 (0%) | ||||
| Platelet count decreased | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/22 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Hypokalaemia | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Hyponatraemia | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1/22 (4.5%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Benign neoplasm | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Diffuse large B-cell lymphoma | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 2/22 (9.1%) | ||||
| Malignant melanoma | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 0/22 (0%) | ||||
| Myelodysplastic syndrome | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Squamous cell carcinoma | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Nervous system disorders | ||||||||
| Aphasia | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/22 (0%) | ||||
| Encephalopathy | 2/3 (66.7%) | 1/3 (33.3%) | 1/6 (16.7%) | 6/22 (27.3%) | ||||
| Seizure | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Renal and urinary disorders | ||||||||
| Renal disorder | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Aspiration | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/22 (0%) | ||||
| Hypoxia | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 2/22 (9.1%) | ||||
| Pleural effusion | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Pneumonitis | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Pneumothorax | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/22 (0%) | ||||
| Respiratory failure | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Rash maculo-papular | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/22 (0%) | ||||
| Swelling face | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Vascular disorders | ||||||||
| Hypotension | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 2/22 (9.1%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| 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) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 3/3 (100%) | 6/6 (100%) | 22/22 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 2/3 (66.7%) | 3/3 (100%) | 4/6 (66.7%) | 13/22 (59.1%) | ||||
| Febrile neutropenia | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 2/22 (9.1%) | ||||
| Leukopenia | 1/3 (33.3%) | 1/3 (33.3%) | 0/6 (0%) | 3/22 (13.6%) | ||||
| Neutropenia | 2/3 (66.7%) | 1/3 (33.3%) | 2/6 (33.3%) | 5/22 (22.7%) | ||||
| Thrombocytopenia | 1/3 (33.3%) | 1/3 (33.3%) | 0/6 (0%) | 2/22 (9.1%) | ||||
| Cardiac disorders | ||||||||
| Atrial fibrillation | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 0/22 (0%) | ||||
| Bradycardia | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 2/22 (9.1%) | ||||
| Sinus bradycardia | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/22 (0%) | ||||
| Sinus tachycardia | 1/3 (33.3%) | 1/3 (33.3%) | 4/6 (66.7%) | 10/22 (45.5%) | ||||
| Tachycardia | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 8/22 (36.4%) | ||||
| Ventricular extrasystoles | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/22 (0%) | ||||
| Ear and labyrinth disorders | ||||||||
| Ear pruritus | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 0/22 (0%) | ||||
| Vertigo | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 2/22 (9.1%) | ||||
| Eye disorders | ||||||||
| Vision blurred | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1/22 (4.5%) | ||||
| Visual impairment | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1/22 (4.5%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal distension | 0/3 (0%) | 1/3 (33.3%) | 1/6 (16.7%) | 0/22 (0%) | ||||
| Abdominal pain | 2/3 (66.7%) | 2/3 (66.7%) | 2/6 (33.3%) | 3/22 (13.6%) | ||||
| Abdominal pain upper | 0/3 (0%) | 1/3 (33.3%) | 1/6 (16.7%) | 0/22 (0%) | ||||
| Anal incontinence | 1/3 (33.3%) | 0/3 (0%) | 1/6 (16.7%) | 0/22 (0%) | ||||
| Constipation | 2/3 (66.7%) | 2/3 (66.7%) | 0/6 (0%) | 4/22 (18.2%) | ||||
| Diarrhoea | 0/3 (0%) | 2/3 (66.7%) | 2/6 (33.3%) | 11/22 (50%) | ||||
| Dry mouth | 1/3 (33.3%) | 1/3 (33.3%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Dyspepsia | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Dysphagia | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/22 (0%) | ||||
| Flatulence | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 0/22 (0%) | ||||
| Hypoaesthesia oral | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/22 (0%) | ||||
| Impaired gastric emptying | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/22 (0%) | ||||
| Nausea | 1/3 (33.3%) | 2/3 (66.7%) | 5/6 (83.3%) | 8/22 (36.4%) | ||||
| Obstruction gastric | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/22 (0%) | ||||
| Oral disorder | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 0/22 (0%) | ||||
| Vomiting | 0/3 (0%) | 2/3 (66.7%) | 3/6 (50%) | 5/22 (22.7%) | ||||
| General disorders | ||||||||
| Application site paraesthesia | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/22 (0%) | ||||
| Asthenia | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 0/22 (0%) | ||||
| Chills | 1/3 (33.3%) | 2/3 (66.7%) | 1/6 (16.7%) | 10/22 (45.5%) | ||||
| Fatigue | 2/3 (66.7%) | 3/3 (100%) | 4/6 (66.7%) | 11/22 (50%) | ||||
| Gait disturbance | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 5/22 (22.7%) | ||||
| Malaise | 0/3 (0%) | 1/3 (33.3%) | 1/6 (16.7%) | 3/22 (13.6%) | ||||
| Non-cardiac chest pain | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 2/22 (9.1%) | ||||
| Oedema | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 2/22 (9.1%) | ||||
| Oedema peripheral | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/22 (0%) | ||||
| Pain | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 2/22 (9.1%) | ||||
| Pyrexia | 3/3 (100%) | 3/3 (100%) | 6/6 (100%) | 21/22 (95.5%) | ||||
| Hepatobiliary disorders | ||||||||
| Hyperbilirubinaemia | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/22 (0%) | ||||
| Immune system disorders | ||||||||
| Hypersensitivity | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 0/22 (0%) | ||||
| Hypogammaglobulinaemia | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 2/22 (9.1%) | ||||
| Cytokine release syndrome | 3/3 (100%) | 3/3 (100%) | 6/6 (100%) | 21/22 (95.5%) | ||||
| Infections and infestations | ||||||||
| Candida infection | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 2/22 (9.1%) | ||||
| Cytomegalovirus infection | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1/22 (4.5%) | ||||
| Dacryocystitis | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 0/22 (0%) | ||||
| Lung infection | 1/3 (33.3%) | 1/3 (33.3%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Oesophageal infection | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/22 (0%) | ||||
| Oral candidiasis | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 2/22 (9.1%) | ||||
| Parotitis | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 2/22 (9.1%) | ||||
| Pneumonia | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 2/22 (9.1%) | ||||
| Upper respiratory tract infection | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1/22 (4.5%) | ||||
| Urinary tract infection | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1/22 (4.5%) | ||||
| Vaginal infection | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/22 (0%) | ||||
| Vulvovaginal mycotic infection | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/22 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Fall | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 0/22 (0%) | ||||
| Post lumbar puncture syndrome | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 0/22 (0%) | ||||
| Procedural pain | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/22 (0%) | ||||
| Urinary tract stoma complication | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/22 (0%) | ||||
| Investigations | ||||||||
| Activated partial thromboplastin time prolonged | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/22 (0%) | ||||
| Alanine aminotransferase increased | 1/3 (33.3%) | 0/3 (0%) | 2/6 (33.3%) | 2/22 (9.1%) | ||||
| Aspartate aminotransferase increased | 1/3 (33.3%) | 0/3 (0%) | 2/6 (33.3%) | 3/22 (13.6%) | ||||
| Blood alkaline phosphatase increased | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/22 (0%) | ||||
| Blood bilirubin increased | 1/3 (33.3%) | 1/3 (33.3%) | 0/6 (0%) | 0/22 (0%) | ||||
| Immunoglobulins decreased | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 0/22 (0%) | ||||
| Interleukin level increased | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/22 (0%) | ||||
| Lymphocyte count decreased | 1/3 (33.3%) | 0/3 (0%) | 2/6 (33.3%) | 2/22 (9.1%) | ||||
| Neutrophil count decreased | 1/3 (33.3%) | 1/3 (33.3%) | 2/6 (33.3%) | 10/22 (45.5%) | ||||
| Platelet count decreased | 1/3 (33.3%) | 0/3 (0%) | 2/6 (33.3%) | 7/22 (31.8%) | ||||
| Transaminases increased | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 3/22 (13.6%) | ||||
| Weight decreased | 1/3 (33.3%) | 2/3 (66.7%) | 0/6 (0%) | 2/22 (9.1%) | ||||
| Weight increased | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/22 (0%) | ||||
| White blood cell count decreased | 1/3 (33.3%) | 1/3 (33.3%) | 1/6 (16.7%) | 3/22 (13.6%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 1/3 (33.3%) | 2/3 (66.7%) | 2/6 (33.3%) | 1/22 (4.5%) | ||||
| Dehydration | 1/3 (33.3%) | 1/3 (33.3%) | 0/6 (0%) | 0/22 (0%) | ||||
| Hyperglycaemia | 1/3 (33.3%) | 1/3 (33.3%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Hypoalbuminaemia | 2/3 (66.7%) | 1/3 (33.3%) | 2/6 (33.3%) | 3/22 (13.6%) | ||||
| Hypocalcaemia | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 0/22 (0%) | ||||
| Hypokalaemia | 2/3 (66.7%) | 2/3 (66.7%) | 1/6 (16.7%) | 3/22 (13.6%) | ||||
| Hypomagnesaemia | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 2/22 (9.1%) | ||||
| Hyponatraemia | 1/3 (33.3%) | 1/3 (33.3%) | 0/6 (0%) | 3/22 (13.6%) | ||||
| Hypophosphataemia | 2/3 (66.7%) | 1/3 (33.3%) | 2/6 (33.3%) | 5/22 (22.7%) | ||||
| Malnutrition | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 0/22 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 2/22 (9.1%) | ||||
| Back pain | 0/3 (0%) | 2/3 (66.7%) | 0/6 (0%) | 2/22 (9.1%) | ||||
| Bone pain | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 2/22 (9.1%) | ||||
| Muscle spasms | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/22 (0%) | ||||
| Muscular weakness | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Myalgia | 0/3 (0%) | 0/3 (0%) | 3/6 (50%) | 1/22 (4.5%) | ||||
| Neck pain | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 2/22 (9.1%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| B-cell lymphoma | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 0/22 (0%) | ||||
| Nervous system disorders | ||||||||
| Aphasia | 1/3 (33.3%) | 1/3 (33.3%) | 1/6 (16.7%) | 3/22 (13.6%) | ||||
| Cognitive disorder | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 0/22 (0%) | ||||
| Disturbance in attention | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 3/22 (13.6%) | ||||
| Dizziness | 1/3 (33.3%) | 1/3 (33.3%) | 1/6 (16.7%) | 4/22 (18.2%) | ||||
| Dysarthria | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 2/22 (9.1%) | ||||
| Dysgeusia | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 3/22 (13.6%) | ||||
| Encephalopathy | 3/3 (100%) | 1/3 (33.3%) | 2/6 (33.3%) | 8/22 (36.4%) | ||||
| Headache | 1/3 (33.3%) | 1/3 (33.3%) | 4/6 (66.7%) | 13/22 (59.1%) | ||||
| Hypoaesthesia | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1/22 (4.5%) | ||||
| Paraesthesia | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/22 (0%) | ||||
| Somnolence | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 2/22 (9.1%) | ||||
| Syncope | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 0/22 (0%) | ||||
| Tremor | 1/3 (33.3%) | 2/3 (66.7%) | 2/6 (33.3%) | 4/22 (18.2%) | ||||
| Psychiatric disorders | ||||||||
| Anxiety | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Confusional state | 1/3 (33.3%) | 1/3 (33.3%) | 0/6 (0%) | 4/22 (18.2%) | ||||
| Insomnia | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 6/22 (27.3%) | ||||
| Mental status changes | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/22 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Dysuria | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 0/22 (0%) | ||||
| Pollakiuria | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 2/22 (9.1%) | ||||
| Urinary incontinence | 1/3 (33.3%) | 0/3 (0%) | 1/6 (16.7%) | 0/22 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Benign prostatic hyperplasia | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 0/22 (0%) | ||||
| Pelvic pain | 0/3 (0%) | 1/3 (33.3%) | 1/6 (16.7%) | 0/22 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 1/3 (33.3%) | 0/3 (0%) | 1/6 (16.7%) | 4/22 (18.2%) | ||||
| Dysphonia | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/22 (0%) | ||||
| Dyspnoea | 1/3 (33.3%) | 0/3 (0%) | 2/6 (33.3%) | 1/22 (4.5%) | ||||
| Hypoxia | 2/3 (66.7%) | 1/3 (33.3%) | 2/6 (33.3%) | 9/22 (40.9%) | ||||
| Nasal congestion | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1/22 (4.5%) | ||||
| Nasal mucosal disorder | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/22 (0%) | ||||
| Oropharyngeal pain | 0/3 (0%) | 1/3 (33.3%) | 1/6 (16.7%) | 2/22 (9.1%) | ||||
| Pleural effusion | 0/3 (0%) | 2/3 (66.7%) | 0/6 (0%) | 5/22 (22.7%) | ||||
| Pneumothorax | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/22 (0%) | ||||
| Productive cough | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1/22 (4.5%) | ||||
| Sinus pain | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1/22 (4.5%) | ||||
| Tachypnoea | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 2/22 (9.1%) | ||||
| Wheezing | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 1/22 (4.5%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Dermatitis contact | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/22 (0%) | ||||
| Hyperhidrosis | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 2/22 (9.1%) | ||||
| Pruritus | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1/22 (4.5%) | ||||
| Rash | 1/3 (33.3%) | 1/3 (33.3%) | 1/6 (16.7%) | 1/22 (4.5%) | ||||
| Vascular disorders | ||||||||
| Flushing | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1/22 (4.5%) | ||||
| Hypertension | 1/3 (33.3%) | 1/3 (33.3%) | 1/6 (16.7%) | 3/22 (13.6%) | ||||
| Hypotension | 3/3 (100%) | 2/3 (66.7%) | 4/6 (66.7%) | 9/22 (40.9%) | ||||
| Orthostatic hypotension | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 3/22 (13.6%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years
Results Point of Contact
| Name/Title | Medical Information |
|---|---|
| Organization | Kite, A Gilead Company |
| Phone | 844-454-5483(1-844-454-KITE) |
| medinfo@kitepharma.com |
Responsible Party:
Kite, A Gilead Company
ClinicalTrials.gov Identifier:
NCT02926833
Other Study ID Numbers:
- KTE-C19-106
First Posted:
Oct 6, 2016
Last Update Posted:
May 23, 2022
Last Verified:
Apr 1, 2022