Refractory Diffuse Large B Cell LymphomaPhase 1/2ZUMA-6NCT02926833
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 study testing KTE-C19, Atezolizumab and Cyclophosphamide in people with Refractory Diffuse Large B Cell Lymphoma, run by Kite, A Gilead Company at 5 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Refractory Diffuse Large B Cell Lymphoma
- What is being tested?
- KTE-C19, Atezolizumab and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 5 sitesUnited States
- Study dates
- 29 Sep 2016to 12 Jan 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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-cluster of differentiate 20 (anti-CD20) monoclonal antibody unless investigator determines that tumor is CD20-negative; and
Show all 12Show fewer
- 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.
Who cannot join
- 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 human immunodeficiency virus (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
Show all 12Show fewer
- 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 Programmed Cell Death Ligand 1 (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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
City of Hope
Duarte, California, 91010
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Stanford Cancer Center
Palo Alto, California, 94305
H Lee Moffitt Cancer Center
Tampa, Florida, 33612
About this study
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)
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).
- Conditions
- Refractory Diffuse Large B Cell Lymphoma
- Being tested
- KTE-C19, Atezolizumab, Cyclophosphamide, Fludarabine
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KTE-C19Biological
Also called Axicabtagene ciloleucel, Yescarta®
A single infusion of KTE-C19 CAR-T cells administered intravenously
AtezolizumabBiological
Administered intravenously
CyclophosphamideDrug
Administered intravenously
FludarabineDrug
Administered intravenously
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 Cohort 1: KTE-C19 + ATZ (After 21 Days of KTE-C19) | Experimental | 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. Receives: Biological: KTE-C19; Biological: Atezolizumab; Drug: Cyclophosphamide; Drug: Fludarabine |
| Phase 1 Cohort 2: KTE-C19 + ATZ (After 14 Days of KTE-C19) | Experimental | 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. Receives: Biological: KTE-C19; Biological: Atezolizumab; Drug: Cyclophosphamide; Drug: Fludarabine |
| Phase 1 Cohort 3: KTE-C19 + ATZ (After 1 Day of KTE-C19) | Experimental | 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. Receives: Biological: KTE-C19; Biological: Atezolizumab; Drug: Cyclophosphamide; Drug: Fludarabine |
| Phase 2: KTE-C19 + ATZ (After 1 Day of KTE-C19) | Experimental | 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. Receives: Biological: KTE-C19; Biological: Atezolizumab; Drug: Cyclophosphamide; Drug: Fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
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.
Measured: Baseline up to 21 days
Phase 1 and 2: Complete Response Rate (CRR)
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.
Measured: From enrollment until first occurrence of CR or PR (maximum duration: 6.2 years)
Secondary outcomes (17)
Phase 1 and 2: Objective Response Rate (ORR)
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.
Measured: From enrollment until first occurrence of CR or PR (maximum duration: 6.2 years)
Phase 1 and 2: Duration of Response (DOR)
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.
Measured: From the date of first confirmed objective response (CR or PR) to disease progression or death regardless of cause (maximum duration: 6.2 years)
Phase 1 and 2: Progression-Free Survival (PFS)
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.
Measured: From the date of first KTE-C19 infusion to disease progression or death regardless of cause (maximum duration: 6.2 years)
Phase 1 and 2: Overall Survival (OS)
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.
Measured: From the date of first KTE-C19 infusion to the date of death regardless of cause (maximum duration: 6.2 years)
Phase 1 and 2: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
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.
Measured: Up to 1.8 years
Phase 1 and 2: Percentage of Participants With Serum Chemistry Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Values
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.
Measured: Up to 1.8 years
Phase 1 and 2: Percentage of Participants With Serum Chemistry Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Values
Post axicabtagene ciloleucel infusion lab toxicities were reported. It included lab toxicities observed on or after the axicabtagene ciloleucel infusion date.
Measured: Up to 1.8 years
Phase 1 and 2: Percentage of Participants With Hematology Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Values
Post axicabtagene ciloleucel infusion lab toxicities were reported. It included lab toxicities observed on or after the axicabtagene ciloleucel infusion date.
Measured: Up to 1.8 years
Phase 1 and 2: Percentage of Participants With Hematology Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Values
Post axicabtagene ciloleucel infusion lab toxicities were reported. It included lab toxicities observed on or after the axicabtagene ciloleucel infusion date.
Measured: Up to 1.8 years
Phase 1 and 2: Peak Anti-CD19 CAR T-Cell (KTE-C19) Level (Maximum Observed Plasma Concentration) in Blood
Measured: 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
Measured: Baseline (pre-conditioning chemotherapy); Day 0 (pre-KTE-C19 infusion); Days 1, 4, 7, 14, 22 , 28, Day 35, 49, 69, and 94 post-KTE-C19 infusion
Phase 1 and 2: Atezolizumab Levels in Blood
Measured: 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
Measured: Baseline (pre-conditioning chemotherapy); Day 0 (pre-KTE-C19 infusion); Days 1, 4, 7, 14, 22 , 28, Day 35, 49, 69, and 94 post-KTE-C19 infusion
Phase 1 and 2: Peak Serum Levels of C-Reactive Protein (CRP) in Blood
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2016 (estimated)
- Study start29 Sep 2016
- Primary completion12 Jan 2023
- Study completion12 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Refractory Diffuse Large B Cell LymphomaStudies of the same condition, open and under way.
- More trials run by Kite, A Gilead CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kite, A Gilead Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Kite Study Director, Study director, Kite, A Gilead Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02926833
- Sponsor's protocol ID
- KTE-C19-106
- Acronym
- ZUMA-6
- Status last verified
- Feb 2024
- First submitted
- 5 Oct 2016
- Last updated
- 6 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Publications
Jacobson CA, Locke FL, Miklos DB, Herrera AF, Westin JR, Lee J, et al. End of Phase 1 results for ZUMA-6: Axicabtagene ciloleucel (axi-cel) in combination with atezolizumab for the treatment of patients with refractory diffuse large B cell lymphoma. Presented at ASH, 2018.
Locke FL, Westin JR, Miklos DB, Herrera AF, Jacobson CA, Lee J, et al. Phase 1 results from ZUMA-6: Axicabtagene ciloleucel (axi-cel; KTE-C19) in combination with atezolizumab for the treatment of patients with refractory diffuse large B cell lymphoma. Presented at ASH, 2018, presentation #2628.
Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
PubMed 34515338
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02926833
- Acronym / sponsor ID
- ZUMA-6 / KTE-C19-106
- Conditions
- Refractory Diffuse Large B Cell Lymphoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Kite, A Gilead CompanyIndustry (pharma, biotech, devices)
- Collaborators
- Genentech, Inc.
- Study start
- 29 Sep 2016 (actual)
- Primary completion
- 12 Jan 2023 (actual)
- Study completion
- 12 Jan 2023 (actual)
- First posted
- 6 Oct 2016 (estimated)
- Results
- Posted 26 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Phase 1 Cohort 1: KTE-C19 + ATZ (After 21 Days of KTE-C19) | Experimental | Biological: KTE-C19, Biological: Atezolizumab, Drug: Cyclophosphamide, Drug: FludarabineParticipants 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. |
| Phase 1 Cohort 2: KTE-C19 + ATZ (After 14 Days of KTE-C19) | Experimental | Biological: KTE-C19, Biological: Atezolizumab, Drug: Cyclophosphamide, Drug: FludarabineParticipants 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. |
| Phase 1 Cohort 3: KTE-C19 + ATZ (After 1 Day of KTE-C19) | Experimental | Biological: KTE-C19, Biological: Atezolizumab, Drug: Cyclophosphamide, Drug: FludarabineParticipants 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. |
| Phase 2: KTE-C19 + ATZ (After 1 Day of KTE-C19) | Experimental | Biological: KTE-C19, Biological: Atezolizumab, Drug: Cyclophosphamide, Drug: FludarabineParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histologically confirmed DLBCL
- Chemotherapy-refractory disease, defined as one or more of the following:
- Individuals must have received adequate prior therapy including at a minimum:
- At least one measurable lesion per revised International Working Group (IWG) Response Criteria
- Age 18 years or older
Key exclusion criteria (12 listed)
- 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 human immunodeficiency virus (HIV) or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KTE-C19Also: Axicabtagene ciloleucel, Yescarta®A single infusion of KTE-C19 CAR-T cells administered intravenously | Biological | Phase 1 Cohort 1: KTE-C19 + ATZ (After 21 Days of KTE-C19), Phase 1 Cohort 2: KTE-C19 + ATZ (After 14 Days of KTE-C19), Phase 1 Cohort 3: KTE-C19 + ATZ (After 1 Day of KTE-C19), Phase 2: KTE-C19 + ATZ (After 1 Day of KTE-C19) |
| AtezolizumabAdministered intravenously | Biological | Phase 1 Cohort 1: KTE-C19 + ATZ (After 21 Days of KTE-C19), Phase 1 Cohort 2: KTE-C19 + ATZ (After 14 Days of KTE-C19), Phase 1 Cohort 3: KTE-C19 + ATZ (After 1 Day of KTE-C19), Phase 2: KTE-C19 + ATZ (After 1 Day of KTE-C19) |
| CyclophosphamideAdministered intravenously | Drug | Phase 1 Cohort 1: KTE-C19 + ATZ (After 21 Days of KTE-C19), Phase 1 Cohort 2: KTE-C19 + ATZ (After 14 Days of KTE-C19), Phase 1 Cohort 3: KTE-C19 + ATZ (After 1 Day of KTE-C19), Phase 2: KTE-C19 + ATZ (After 1 Day of KTE-C19) |
| FludarabineAdministered intravenously | Drug | Phase 1 Cohort 1: KTE-C19 + ATZ (After 21 Days of KTE-C19), Phase 1 Cohort 2: KTE-C19 + ATZ (After 14 Days of KTE-C19), Phase 1 Cohort 3: KTE-C19 + ATZ (After 1 Day of KTE-C19), Phase 2: KTE-C19 + ATZ (After 1 Day of KTE-C19) |
Primary outcome
Phase 1: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
Time frame: 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)
Time frame: From enrollment until first occurrence of CR or PR (maximum duration: 6.2 years)
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.
17 secondary outcomes
Phase 1 and 2: Objective Response Rate (ORR)
Time frame: From enrollment until first occurrence of CR or PR (maximum duration: 6.2 years)
Phase 1 and 2: Duration of Response (DOR)
Time frame: From the date of first confirmed objective response (CR or PR) to disease progression or death regardless of cause (maximum duration: 6.2 years)
Phase 1 and 2: Progression-Free Survival (PFS)
Time frame: From the date of first KTE-C19 infusion to disease progression or death regardless of cause (maximum duration: 6.2 years)
Phase 1 and 2: Overall Survival (OS)
Time frame: From the date of first KTE-C19 infusion to the date of death regardless of cause (maximum duration: 6.2 years)
Phase 1 and 2: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
Time frame: Up to 1.8 years
Phase 1 and 2: Percentage of Participants With Serum Chemistry Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Values
Time frame: Up to 1.8 years
Phase 1 and 2: Percentage of Participants With Serum Chemistry Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Values
Time frame: Up to 1.8 years
Phase 1 and 2: Percentage of Participants With Hematology Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Values
Time frame: Up to 1.8 years
Phase 1 and 2: Percentage of Participants With Hematology Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Values
Time frame: Up to 1.8 years
Phase 1 and 2: Peak Anti-CD19 CAR T-Cell (KTE-C19) Level (Maximum Observed Plasma Concentration) in Blood
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
Phase 1 and 2: Percentage of Participants With Anti-KTE-C19 Antibodies
Time frame: Baseline (pre-conditioning chemotherapy); Day 0 (pre-KTE-C19 infusion); Days 1, 4, 7, 14, 22 , 28, Day 35, 49, 69, and 94 post-KTE-C19 infusion
Phase 1 and 2: Atezolizumab Levels in Blood
Time frame: 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
Time frame: Baseline (pre-conditioning chemotherapy); Day 0 (pre-KTE-C19 infusion); Days 1, 4, 7, 14, 22 , 28, Day 35, 49, 69, and 94 post-KTE-C19 infusion
Phase 1 and 2: Peak Serum Levels of C-Reactive Protein (CRP) in Blood
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
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
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
Phase 1 and 2: Peak Serum Levels of Ferritin in Blood
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
Phase 1 and 2: Peak Serum Levels of Interleukin-2 Receptor Alpha (IL-2Rα) in Blood
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundJacobson CA, Locke FL, Miklos DB, Herrera AF, Westin JR, Lee J, et al. End of Phase 1 results for ZUMA-6: Axicabtagene ciloleucel (axi-cel) in combination with atezolizumab for the treatment of patients with refractory diffuse large B cell lymphoma. Presented at ASH, 2018.
- BackgroundLocke FL, Westin JR, Miklos DB, Herrera AF, Jacobson CA, Lee J, et al. Phase 1 results from ZUMA-6: Axicabtagene ciloleucel (axi-cel; KTE-C19) in combination with atezolizumab for the treatment of patients with refractory diffuse large B cell lymphoma. Presented at ASH, 2018, presentation #2628.
- Derived from this study: PubMed 34515338Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
- Gilead Clinical Trials WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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
Related trials for Refractory Diffuse Large B Cell Lymphoma
Active, not recruitingEarly Phase 1
Iomab-ACT: A Pilot Study of 131-I Apamistamab Followed by CD19-Targeted CAR T-Cell Therapy for Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia or Diffuse Large B-Cell Lymphoma
B-ALL, DLBCL
RecruitingPhase 2
Testing the Effectiveness of a Combination Targeted Therapy (ViPOR) for Patients With Relapsed and/or Refractory Aggressive B-cell Lymphoma
High Grade B-Cell Lymphoma With MYC and BCL6 Rearrangements, Recurrent Diffuse Large B-Cell Lymphoma
RecruitingPhase 1/2
Dose Escalation and Dose Expansion Study of MDX2003 in Patients With Different Types of Lymphoma
Lymphoma, Waldenström Macroglobulinemia (WM)
RecruitingPhase 1/2
Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (ViPOR) in Relapsed/Refractory B-cell Lymphoma
Lymphoma, Non-Hodgkin Lymphoma
Not yet recruitingPhase 2/3
A Clinical Trial of MK-1045 With Zilovertamab Vedotin in Participants With Diffuse Large B-cell Lymphoma (MK-1045-010)
Lymphoma, Large B-Cell, Diffuse, Diffuse Large B-Cell Lymphoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kite Study Director study director
Kite, A Gilead Company
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing KTE-C19, Atezolizumab and Cyclophosphamide in people with Refractory Diffuse Large B Cell Lymphoma, run by Kite, A Gilead Company at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) (time frame: Baseline up to 21 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02926833, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2024.