Fred Hutch/University of Washington Cancer Consortium
Brief Title
JCAR014 and Durvalumab in Treating Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma
Official Title
A Phase 1b Study of JCAR014, Autologous T Cells Engineered to Express a CD19-Specific Chimeric Antigen Receptor, in Combination With Durvalumab (MEDI4736) for Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma
Acronym
Not provided
Organization
Fred Hutchinson Cancer CenterOTHER
Status Module
Record Verification Date
Aug 2022
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Terminated due to slow accrual.
Expanded Access Info
No
Start Date
Nov 15, 2016Actual
Primary Completion Date
May 28, 2021Actual
Completion Date
May 28, 2021Actual
First Submitted Date
Feb 24, 2016
First Submission Date that Met QC Criteria
Mar 7, 2016
First Posted Date
Mar 11, 2016Estimated
Results Waived
Not provided
Results First Submitted Date
May 6, 2022
Results First Submitted that Met QC Criteria
Aug 1, 2022
Results First Posted Date
Aug 24, 2022Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Aug 1, 2022
Last Update Posted Date
Aug 24, 2022Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Alexandre Hirayama, Research Associate, Fred Hutchinson Cancer CenterPrincipal Investigator
Lead Sponsor
Fred Hutchinson Cancer CenterOTHER
Collaborators
Name
Class
AstraZeneca
INDUSTRY
Juno Therapeutics, Inc., a Bristol-Myers Squibb Company
INDUSTRY
MedImmune LLC
INDUSTRY
National Cancer Institute (NCI)
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This phase Ib trial studies whether anti-CD19-chimeric antigen receptor (CAR) lentiviral vector-transduced autologous T cells (JCAR014) and durvalumab are safe in combination and can work together in treating patients with non-Hodgkin lymphoma that has returned after a period of improvement (relapsed) or has not responded to previous treatment (refractory). JCAR014 is made of each patient's immune cells (T cells) that have a new gene added to them in a laboratory, which programs them to kill lymphoma cells. Durvalumab is a type of drug called a monoclonal antibody, targeted to PD-L1 that may help immune cells attack cancer cells more effectively and thus help JCAR014 work better.
Detailed Description
PRIMARY OBJECTIVES:
I. To evaluate the safety of JCAR014 in combination with durvalumab in adult patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL).
II. To determine the maximum tolerated dose (MTD) of durvalumab in combination with JCAR014.
III. To characterize the pharmacokinetic (PK) profile of JCAR014.
SECONDARY OBJECTIVES:
I. To assess the antitumor activity of JCAR014 in combination with durvalumab in R/R B-cell NHL.
II. To estimate the duration of response (DOR), progression-free survival (PFS), and overall survival (OS) in patients treated with JCAR014 in combination with durvalumab.
III. To characterize the PK profile of durvalumab. IV. To assess the immunogenicity of JCAR014 and durvalumab.
EXPLORATORY OBJECTIVE:
I. To assess the pharmacodynamic effects of JCAR014 and durvalumab in blood and within the tumor.
OUTLINE: This is a dose-escalation study of durvalumab administered with a single fixed dose of JCAR014. Patients are assigned to 1 of 2 treatment arms, listed as Groups 1 and 2 below.
LYMPHODEPLETING CHEMOTHERAPY: All patients receive cyclophosphamide and fludarabine intravenously (IV) for 3 days starting approximately on day -5 or day -4.
GROUP I: Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
GROUP II: Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 30 days for 30 months, every 3 months for 12 months, then periodically for at least 15 years.
Conditions Module
Conditions
Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
Recurrent Diffuse Large B-Cell Lymphoma
Recurrent Primary Mediastinal (Thymic) Large B-Cell Lymphoma
Refractory Diffuse Large B-Cell Lymphoma
Refractory High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements
Refractory Primary Mediastinal (Thymic) Large B-Cell Lymphoma
Keywords
PD-L1
immunotherapy
non-Hodgkin lymphoma
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
30Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Group I (JCAR014, durvalumab) Early - Dose Level 2
Experimental
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - early: start durvalumab no earlier than 7 days after JCAR014.
Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014
Drug: Cyclophosphamide
Biological: Durvalumab
Drug: Fludarabine
Group I (JCAR014, durvalumab) Late- Dose Level 1
Experimental
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - late: start durvalumab no earlier than 21 days after JCAR014
Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
.
Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014
Drug: Cyclophosphamide
Biological: Durvalumab
Drug: Fludarabine
Group I (JCAR014, durvalumab) Late - Dose Level 2
Experimental
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - late: start durvalumab no earlier than 21 days after JCAR014
Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014
Biological
Given IV
Group I (JCAR014, durvalumab) Early - Dose Level 2
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Count of Participants Who Experienced Adverse Events
Toxicity graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03.
28 days post last infusion of Durvalumab, up to 1 year
Dose Limiting Toxicity (DLT) Rates
Will be summarized based on the dose limiting toxicity evaluable analysis set. The target toxicity rate for the maximum tolerated dose is 30%. Outcome will be reported as a count of patients in each arm that experienced a DLT.
28 days post first infusion of Durvalumab (for participants in Group 1) or 28 days post infusion of JCAR (for participants in Group 2)
Highest Treatment Dose Administered on Study
Reporting outcome as the maximum durvalumab dose that we reached on the study. Patients were monitored for 28 days post infusion for dose limiting toxicities. The DLT rate was used to determine dose escalation. The study was terminated prior to reaching the maximum tolerated dose.
28 days
Maximum JCAR014 Cmax by Flow Cytometry
Absolute CD4+ and CD8+ CAR-T cell counts were determined by multiplying the percentages of CD3+CD4+CD8-EGFRt+ and CD3+CD4-CD8+EGFRt+ events, respectively, in a viable CD45+ lymphocyte forward/side scatter gate by an absolute lymphocyte count performed on the same day. Excluding 1 patient in Group 2 Dose Level 5 who received an out-of-specification JCAR014 product.
Up to 12 months
Area Under the Curve (AUC) of JCAR014 by Flow Cytometry
Absolute CD4+ and CD8+ CAR-T cell counts were determined by multiplying the percentages of CD3+CD4+CD8-EGFRt+ and CD3+CD4-CD8+EGFRt+ events, respectively, in a viable CD45+ lymphocyte forward/side scatter gate by an absolute lymphocyte count performed on the same day. Subjects had samples analyzed at approximately days 0, 3, 7, 10, 14, 21, and 28 after CAR-T cell infusion to generate the AUC from day 0 to 28. The areas under the curve of CAR T-cell counts by flow cytometry and qPCR between time points were calculated by using a trapezoidal rule computational algorithm. Excluding 1 patient in Group 2 Dose Level 5 who received an out-of-specification JCAR014 product.
Secondary Outcomes
Measure
Description
Time Frame
Rate of Complete Response (CR) by Investigator Assessment Using Lugano Criteria
This outcome is a count of participants who experienced a best response of complete response (CR) by investigator assessment using Lugano criteria. 1 patient in Group 1 Early Dose Level 2 could not be analyzed for the outcome because they expired before their first response assessment.
Up to 1 year
Other Outcomes
Measure
Description
Time Frame
B-cell Depletion in Circulation, Profile of Soluble Circulating Proteins Such as Cytokines and Chemokines, and Changes in the Level of Detectable Soluble PD-L1
Up to 12 months
Change in the Phenotype of Tumor Cells (e.g., Expression of PD-L1) and of the Tumor Microenvironment (e.g., Infiltration by Chimeric Antigen Receptor [CAR] T Cells)
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
INCLUSION CRITERIA FOR SCREENING:
Relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS); high grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements; primary mediastinal B-cell lymphoma (PMBCL); or DLBCL transformed from indolent histology with one of the following:
Persistent disease after first-line chemo-immunotherapy
Relapse after first-line chemo-immunotherapy and not eligible for autologous hematopoietic stem cell transplant (HCT)
Relapse or persistent disease after at least two lines of therapy or after autologous HCT
Ability to understand and provide informed consent
INCLUSION CRITERIA FOR LEUKAPHERESIS AND PRE-THERAPY EVALUATION:
Screening evaluation appropriate for leukapheresis and T-cell collection
Evidence of CD19 expression on any prior or current tumor specimen or a high likelihood of CD19 expression based on disease histology
INCLUSION CRITERIA FOR LYMPHODEPLETION CHEMOTHERAPY, JCAR014 AND DURVALUMAB:
Successful collection of T cells for JCAR014 manufacturing
Documentation of CD19 expression on any prior or current tumor biopsy
Assessed by the investigator to have adequate bone marrow function to receive lymphodepleting conditioning chemotherapy
Serum creatinine < 1.5 x age-adjusted upper limit of normal (ULN)
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 x ULN and total bilirubin =< 2 x ULN
Adequate pulmonary function, defined as Common Terminology Criteria for Adverse Events (CTCAE) grade =< 1 dyspnea and oxygen saturation (SaO2) >= 92% on room air; patients with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing and must have a forced expiratory volume in 1 second (FEV1) >= 50% of predicted value or diffusing capacity of the lung for carbon monoxide (DLCO; corrected) >= 40% of predicted value
Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) >= 35% as assessed by echocardiogram (ECHO) or multiple uptake gated acquisition (MUGA)
Women of reproductive potential (defined as all women physiologically capable of becoming pregnant) must agree to use suitable methods of contraception for 90 days after the last dose of study therapy (durvalumab or JCAR014)
Males who have partners of reproductive potential must agree to use an effective barrier contraceptive method for 90 days after the last dose of study therapy (durvalumab or JCAR014)
Exclusion Criteria:
EXCLUSION CRITERIA FOR SCREENING:
Subjects with known active central nervous system (CNS) involvement by malignancy; subjects with prior CNS disease that has been effectively treated will be eligible if treatment was completed at least 3 months prior to enrollment and there is no evidence of disease or stable abnormalities on repeat imaging
Planned use of corticosteroids (> 10 mg/day prednisone or equivalent) or other systemic immunosuppression within 4 days prior to leukapheresis; topical and/or inhaled steroids are permitted
Prior treatment with any CD19 CAR T-cell therapy
Prior allogeneic HCT
Known active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection
Pregnant or breastfeeding women
Known exclusion criteria for leukapheresis, JCAR014, or durvalumab therapy
EXCLUSION CRITERIA FOR LEUKAPHERESIS AND PRE-THERAPY EVALUATION:
Subjects with known active central nervous system (CNS) involvement by malignancy; subjects with prior CNS disease that has been effectively treated will be eligible if treatment was completed at least 3 months prior to enrollment and there is no evidence of disease or stable abnormalities on repeat imaging
Prior treatment with programmed cell death (PD)-1, PD-ligand (L)1, cytotoxic T lymphocyte-associated protein 4 (CTLA 4) targeted therapy, or tumor necrosis factor receptor superfamily (TNFRSF) agonists including CD134 (OX40), CD27, CD137 (4-1BB), and CD357 (glucocorticoid-induced tumor necrosis factor receptor family-related protein [GITR])
Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., ulcerative colitis, Crohn's disease], celiac disease, or other serious chronic gastrointestinal conditions associated with diarrhea; autoimmune vasculitis; systemic lupus erythematosus; Wegener syndrome [granulomatosis with polyangiitis]; myasthenia gravis; Graves' disease; rheumatoid arthritis, hypophysitis, uveitis, etc.) within 3 years prior to the planned start of treatment; the following are exceptions to this criterion:
Vitiligo
Alopecia
Hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
Psoriasis not requiring systemic treatment
Other conditions considered to be low risk of serious deterioration by the principal investigator (PI)
History of any one of the following cardiovascular conditions within the past 6 months: class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, or unstable angina; history of other clinically significant cardiac disease that, in the opinion of the PI or designee, is a contraindication to lymphodepleting chemotherapy, JCAR014 infusion, or durvalumab infusion is also excluded
History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, or psychosis; history of other organic brain syndrome that in the opinion of the PI or designee is a contraindication to lymphodepleting chemotherapy, JCAR014 infusion or durvalumab infusion
History of solid organ transplantation
EXCLUSION CRITERIA FOR LYMPHODEPLETION CHEMOTHERAPY, JCAR014 AND DURVALUMAB:
For lymphodepletion chemotherapy, JCAR014 and durvalumab: Subjects with known active CNS involvement by malignancy; subjects with prior CNS disease that has been effectively treated will be eligible if treatment was completed at least 3 months prior to enrollment and there is no evidence of disease or stable abnormalities on repeat imaging
Uncontrolled infection
Receipt of live, attenuated vaccine within 28 days prior to the first dose of durvalumab (Note: enrolled patients should not receive live vaccine during the study and for 180 days after the last dose of durvalumab)
Planned use of corticosteroids (> 10 mg/day prednisone or equivalent) or other systemic immunosuppression is not permitted within 72 hours prior to JCAR014 infusion; topical and/or inhaled steroids are permitted.
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
Not provided
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Jordan Gauthier
Fred Hutch/University of Washington Cancer Consortium
Principal Investigator
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Fred Hutch/University of Washington Cancer Consortium
Hirayama AV, Kimble EL, Wright JH, Fiorenza S, Gauthier J, Voutsinas JM, Wu Q, Yeung CCS, Gazeau N, Pender BS, Kirchmeier DR, Torkelson A, Chutnik AN, Cassaday RD, Chapuis AG, Green DJ, Kiem HP, Milano F, Shadman M, Till BG, Riddell SR, Maloney DG, Turtle CJ. Timing of anti-PD-L1 antibody initiation affects efficacy/toxicity of CD19 CAR T-cell therapy for large B-cell lymphoma. Blood Adv. 2024 Jan 23;8(2):453-467. doi: 10.1182/bloodadvances.2023011287.
One patient was enrolled on the trial but did not move on to treatment. They were not assigned to an arm or to a treatment dose level.
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Group I (JCAR014, Durvalumab) Early - Dose Level 2
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - early: start durvalumab no earlier than 7 days after JCAR014.
Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
0
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot_SAP
Yes
Yes
No
Study Protocol and Statistical Analysis Plan
Dec 22, 2021
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
NIH
Non-Randomized
Intervention Model
Sequential Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014
Drug: Cyclophosphamide
Biological: Durvalumab
Drug: Fludarabine
Group II (durvalumab, JCAR014) - Dose Level 1
Experimental
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014
Drug: Cyclophosphamide
Biological: Durvalumab
Drug: Fludarabine
Group II (durvalumab, JCAR014) - Dose Level 2
Experimental
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014
Drug: Cyclophosphamide
Biological: Durvalumab
Drug: Fludarabine
Group II (durvalumab, JCAR014) - Dose Level 3
Experimental
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells
Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014
Drug: Cyclophosphamide
Biological: Durvalumab
Drug: Fludarabine
Group II (durvalumab, JCAR014) - Dose Level 4
Experimental
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014
Drug: Cyclophosphamide
Biological: Durvalumab
Drug: Fludarabine
Group II (durvalumab, JCAR014) - Dose Level 5
Experimental
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014
Drug: Cyclophosphamide
Biological: Durvalumab
Drug: Fludarabine
Group I (JCAR014, durvalumab) Late - Dose Level 2
Group I (JCAR014, durvalumab) Late- Dose Level 1
Group II (durvalumab, JCAR014) - Dose Level 1
Group II (durvalumab, JCAR014) - Dose Level 2
Group II (durvalumab, JCAR014) - Dose Level 3
Group II (durvalumab, JCAR014) - Dose Level 4
Group II (durvalumab, JCAR014) - Dose Level 5
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ CM T-lymphocytes JCAR014
JCAR014
Cyclophosphamide
Drug
Given IV
Group I (JCAR014, durvalumab) Early - Dose Level 2
Group I (JCAR014, durvalumab) Early - Dose Level 2
Group I (JCAR014, durvalumab) Late - Dose Level 2
Group I (JCAR014, durvalumab) Late- Dose Level 1
Group II (durvalumab, JCAR014) - Dose Level 1
Group II (durvalumab, JCAR014) - Dose Level 2
Group II (durvalumab, JCAR014) - Dose Level 3
Group II (durvalumab, JCAR014) - Dose Level 4
Group II (durvalumab, JCAR014) - Dose Level 5
Imfinzi
Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer
MEDI-4736
MEDI4736
Fludarabine
Drug
Given IV
Group I (JCAR014, durvalumab) Early - Dose Level 2
Group I (JCAR014, durvalumab) Late - Dose Level 2
Group I (JCAR014, durvalumab) Late- Dose Level 1
Group II (durvalumab, JCAR014) - Dose Level 1
Group II (durvalumab, JCAR014) - Dose Level 2
Group II (durvalumab, JCAR014) - Dose Level 3
Group II (durvalumab, JCAR014) - Dose Level 4
Group II (durvalumab, JCAR014) - Dose Level 5
2-Fluorovidarabine
Fluradosa
Up to 28 days
Maximum JCAR014 Cmax in Blood by Quantitative Polymerase Chain Reaction (qPCR) Analysis
The number of copies of the CAR transgene/μg of DNA in the blood was determined by using quantitative polymerase chain reaction (qPCR) to detect the integrated Flap-EF1⍺ sequence, with a lower limit of detection of 10 transgene copies/μg of DNA. Excluding 1 patient in Group 2 Dose Level 5 who received an out-of-specification JCAR014 product.
Up to 12 months
AUC of JCAR014 Cells by qPCR Analysis
The number of copies of the CAR transgene/μg of DNA in the blood was determined by using quantitative polymerase chain reaction (qPCR) to detect the integrated Flap-EF1⍺ sequence, with a lower limit of detection of 10 transgene copies/μg of DNA. Subjects had samples analyzed at approximately days 0, 3, 7, 10, 14, 21, and 28 after CAR-T cell infusion to generate the AUC from day 0 to 28.The areas under the curve of CAR T-cell counts by flow cytometry and qPCR between time points were calculated by using a trapezoidal rule computational algorithm. Excluding 1 patient in Group 2 Dose Level 5 who received an out-of-specification JCAR014 product.
Up to 28 days
Time to Loss of JCAR014 Detection in Blood by qPCR Analysis
The number of copies of the CAR transgene/μg of DNA in the blood was determined by using quantitative polymerase chain reaction (qPCR) to detect the integrated Flap-EF1⍺ sequence, with a lower limit of detection of 10 transgene copies/μg of DNA. Excluding 1 patient in Group 2 Dose Level 5 who received an out-of-specification JCAR014 product.
Up to 12 months, +/- 30 days
Rate of Partial Response (PR) by Investigator Assessment Using Lugano Criteria
This outcome is a count of participants who experienced a best response of partial response (PR) by investigator assessment using Lugano criteria. 1 patient in Group 1 Early Dose Level 2 could not be analyzed for the outcome because they expired before their first response assessment.
Up to 1 year
Objective Response Rate by Investigator Assessment Using Lugano Criteria
ORR, defined as a count of participant with a best response of either complete response or partial response. 1 patient in Group 1 Early Dose Level 2 could not be analyzed for the outcome because they expired before their first response assessment.
Up to 1 year
Duration of Response
Duration of response will be an average amount of days from first response assessment until progression or death for treated patients. Total number analyzed will be the patients that progressed or died, excluding those that did not progress or die. 1 patient in Group 1 Early Dose Level 2 could not be analyzed for the outcome because they expired before their first response assessment.
From first response to progressive disease or death, assessed up to 1 year
Progression Free Survival
Outcome will be reported as a count of those who did not progress and did not die while on study.
From date of first study treatment to progressive disease or death, assessed up to 1 year
Overall Survival
Outcome will be reported as a count of participants who survived while on study. Survival was assessed up to 1 year.
From date of first study treatment to death, assessed up to 1 year
Flow cytometry may be used in the blood, bone marrow, and cerebrospinal fluid (CSF) (if applicable).
Baseline up to 12 months
Phenotype and/or Genetic Profile of Endogenous Immune Cells and CAR T Cells
Flow cytometry may be used in the blood, bone marrow, and CSF (if applicable).
Up to 12 months
Cmax of Durvalumab in Serum
Up to 12 months
AUC of Durvalumab in Serum
Up to 12 months
Clearance of Durvalumab in Serum
Up to 12 months
Terminal Half-life of Durvalumab in Serum
Up to 12 months
Antibodies and Cellular Immune Responses to JCAR014
Cellular immune responses to JCAR014 will be considered in patients who have two consecutive negative assays for JCAR014 or who have recovered endogenous B cells. Cellular responses to JCAR014 will be evaluated by assessing reactivity of patient peripheral T cells to JCAR014. Peripheral blood will be collected for these studies.
Up to 12 months
Anti-drug Antibodies Directed Against Durvalumab
Will be assessed using a validated immunoassay in serum samples.
Up to 12 months
Derived
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.
FG001
Group I (JCAR014, Durvalumab) Late- Dose Level 1
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - late: start durvalumab no earlier than 21 days after JCAR014
Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
FG002
Group I (JCAR014, Durvalumab) Late - Dose Level 2
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - late: start durvalumab no earlier than 21 days after JCAR014
Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
FG003
Group II (Durvalumab, JCAR014) - Dose Level 1
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
FG004
Group II (Durvalumab, JCAR014) - Dose Level 2
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
FG005
Group II (Durvalumab, JCAR014) - Dose Level 3
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells
FG006
Group II (Durvalumab, JCAR014) - Dose Level 4
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
FG007
Group II (Durvalumab, JCAR014) - Dose Level 5
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
FG0005 subjects
FG0013 subjects
FG0023 subjects
FG0031 subjects
FG0041 subjects
FG0053 subjects
FG0066 subjects
FG0077 subjects
COMPLETED
FG0001 subjects
FG0011 subjects
FG0023 subjects
FG0030 subjects
FG0041 subjects
FG0052 subjects
FG0063 subjects
FG0071 subjects
NOT COMPLETED
FG0004 subjects
FG0012 subjects
FG0020 subjects
FG0031 subjects
FG0040 subjects
FG0051 subjects
FG0063 subjects
FG0076 subjects
Type
Comment
Reasons
Death
FG0003 subjects
FG0012 subjects
FG0020 subjects
FG0031 subjects
FG0040 subjects
FG0050 subjects
FG0063 subjects
FG0074 subjects
Disease progression
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Pt moved to new therapy
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Physician Decision
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Group I (JCAR014, Durvalumab) Early - Dose Level 2
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - early: start durvalumab no earlier than 7 days after JCAR014.
Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
BG001
Group I (JCAR014, Durvalumab) Late- Dose Level 1
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - late: start durvalumab no earlier than 21 days after JCAR014
Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
BG002
Group I (JCAR014, Durvalumab) Late - Dose Level 2
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - late: start durvalumab no earlier than 21 days after JCAR014
Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
BG003
Group II (Durvalumab, JCAR014) - Dose Level 1
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
BG004
Group II (Durvalumab, JCAR014) - Dose Level 2
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
BG005
Group II (Durvalumab, JCAR014) - Dose Level 3
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells
BG006
Group II (Durvalumab, JCAR014) - Dose Level 4
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
BG007
Group II (Durvalumab, JCAR014) - Dose Level 5
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
BG008
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0005
BG0013
BG0023
BG0031
BG0041
BG0053
BG0066
BG0077
BG00829
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Categorical
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
<=18 years
BG0000
BG0010
BG0020
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0002
BG0010
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0000
BG0010
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Count of Participants Who Experienced Adverse Events
Toxicity graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03.
Posted
Count of Participants
Participants
28 days post last infusion of Durvalumab, up to 1 year
ID
Title
Description
OG000
Group I (JCAR014, Durvalumab) Early - Dose Level 2
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - early: start durvalumab no earlier than 7 days after JCAR014.
Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG001
Group I (JCAR014, Durvalumab) Late- Dose Level 1
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - late: start durvalumab no earlier than 21 days after JCAR014
Group 1 Dose Level 2 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
.
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG002
Group I (JCAR014, Durvalumab) Late - Dose Level 2
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - late: start durvalumab no earlier than 21 days after JCAR014
Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG003
Group II (Durvalumab, JCAR014) - Dose Level 1
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG004
Group II (Durvalumab, JCAR014) - Dose Level 2
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG005
Group II (Durvalumab, JCAR014) - Dose Level 3
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG006
Group II (Durvalumab, JCAR014) - Dose Level 4
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG007
Group II (Durvalumab, JCAR014) - Dose Level 5
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
Units
Counts
Participants
OG0005
OG0013
OG0023
OG003
Title
Denominators
Categories
Title
Measurements
OG0005
OG0013
OG0023
OG003
Primary
Dose Limiting Toxicity (DLT) Rates
Will be summarized based on the dose limiting toxicity evaluable analysis set. The target toxicity rate for the maximum tolerated dose is 30%. Outcome will be reported as a count of patients in each arm that experienced a DLT.
Posted
Count of Participants
Participants
28 days post first infusion of Durvalumab (for participants in Group 1) or 28 days post infusion of JCAR (for participants in Group 2)
ID
Title
Description
OG000
Group I (JCAR014, Durvalumab) Early - Dose Level 2
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - early: start durvalumab no earlier than 7 days after JCAR014.
Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG001
Group I (JCAR014, Durvalumab) Late- Dose Level 1
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - late: start durvalumab no earlier than 21 days after JCAR014
Group 1 Dose Level 2 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
.
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
Primary
Highest Treatment Dose Administered on Study
Reporting outcome as the maximum durvalumab dose that we reached on the study. Patients were monitored for 28 days post infusion for dose limiting toxicities. The DLT rate was used to determine dose escalation. The study was terminated prior to reaching the maximum tolerated dose.
Posted
Number
mg
28 days
ID
Title
Description
OG000
All Treated Patients
Arm contains all treated patients on study
Units
Counts
Participants
OG00029
Primary
Maximum JCAR014 Cmax by Flow Cytometry
Absolute CD4+ and CD8+ CAR-T cell counts were determined by multiplying the percentages of CD3+CD4+CD8-EGFRt+ and CD3+CD4-CD8+EGFRt+ events, respectively, in a viable CD45+ lymphocyte forward/side scatter gate by an absolute lymphocyte count performed on the same day. Excluding 1 patient in Group 2 Dose Level 5 who received an out-of-specification JCAR014 product.
Posted
Mean
Full Range
CD3+ CAR-T cells/μL
Up to 12 months
ID
Title
Description
OG000
Group I (JCAR014, Durvalumab) - Dose Level 1
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
OG001
Group I (JCAR014, Durvalumab) - Dose Level 2
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 Dose Level 2 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
OG002
Group II (Durvalumab, JCAR014) - Dose Level 1
Primary
Area Under the Curve (AUC) of JCAR014 by Flow Cytometry
Absolute CD4+ and CD8+ CAR-T cell counts were determined by multiplying the percentages of CD3+CD4+CD8-EGFRt+ and CD3+CD4-CD8+EGFRt+ events, respectively, in a viable CD45+ lymphocyte forward/side scatter gate by an absolute lymphocyte count performed on the same day. Subjects had samples analyzed at approximately days 0, 3, 7, 10, 14, 21, and 28 after CAR-T cell infusion to generate the AUC from day 0 to 28. The areas under the curve of CAR T-cell counts by flow cytometry and qPCR between time points were calculated by using a trapezoidal rule computational algorithm. Excluding 1 patient in Group 2 Dose Level 5 who received an out-of-specification JCAR014 product.
Posted
Mean
Full Range
Days x CD3+ CAR-T cells/μL
Up to 28 days
ID
Title
Description
OG000
Group I (JCAR014, Durvalumab) - Dose Level 1
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
OG001
Group I (JCAR014, Durvalumab) - Dose Level 2
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 Dose Level 2 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
Primary
Maximum JCAR014 Cmax in Blood by Quantitative Polymerase Chain Reaction (qPCR) Analysis
The number of copies of the CAR transgene/μg of DNA in the blood was determined by using quantitative polymerase chain reaction (qPCR) to detect the integrated Flap-EF1⍺ sequence, with a lower limit of detection of 10 transgene copies/μg of DNA. Excluding 1 patient in Group 2 Dose Level 5 who received an out-of-specification JCAR014 product.
Posted
Mean
Full Range
CAR transgene copies/μg DNA
Up to 12 months
ID
Title
Description
OG000
Group I (JCAR014, Durvalumab) - Dose Level 1
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
OG001
Group I (JCAR014, Durvalumab) - Dose Level 2
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 Dose Level 2 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
OG002
Group II (Durvalumab, JCAR014) - Dose Level 1
Primary
AUC of JCAR014 Cells by qPCR Analysis
The number of copies of the CAR transgene/μg of DNA in the blood was determined by using quantitative polymerase chain reaction (qPCR) to detect the integrated Flap-EF1⍺ sequence, with a lower limit of detection of 10 transgene copies/μg of DNA. Subjects had samples analyzed at approximately days 0, 3, 7, 10, 14, 21, and 28 after CAR-T cell infusion to generate the AUC from day 0 to 28.The areas under the curve of CAR T-cell counts by flow cytometry and qPCR between time points were calculated by using a trapezoidal rule computational algorithm. Excluding 1 patient in Group 2 Dose Level 5 who received an out-of-specification JCAR014 product.
Posted
Mean
Full Range
CAR transgene copies/μg DNA x days
Up to 28 days
ID
Title
Description
OG000
Group I (JCAR014, Durvalumab) - Dose Level 1
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
OG001
Group I (JCAR014, Durvalumab) - Dose Level 2
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 Dose Level 2 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
Primary
Time to Loss of JCAR014 Detection in Blood by qPCR Analysis
The number of copies of the CAR transgene/μg of DNA in the blood was determined by using quantitative polymerase chain reaction (qPCR) to detect the integrated Flap-EF1⍺ sequence, with a lower limit of detection of 10 transgene copies/μg of DNA. Excluding 1 patient in Group 2 Dose Level 5 who received an out-of-specification JCAR014 product.
Participants analyzed are the participants with documented loss of detection of JCAR014 in blood by qPCR during follow-up.
Posted
Mean
Full Range
days
Up to 12 months, +/- 30 days
ID
Title
Description
OG000
Group I (JCAR014, Durvalumab) - Dose Level 1
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
OG001
Group I (JCAR014, Durvalumab) - Dose Level 2
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 Dose Level 2 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
OG002
Secondary
Rate of Complete Response (CR) by Investigator Assessment Using Lugano Criteria
This outcome is a count of participants who experienced a best response of complete response (CR) by investigator assessment using Lugano criteria. 1 patient in Group 1 Early Dose Level 2 could not be analyzed for the outcome because they expired before their first response assessment.
Posted
Count of Participants
Participants
Up to 1 year
ID
Title
Description
OG000
Group I (JCAR014, Durvalumab) Early - Dose Level 2
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - early: start durvalumab no earlier than 7 days after JCAR014.
Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG001
Group I (JCAR014, Durvalumab) Late- Dose Level 1
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - late: start durvalumab no earlier than 21 days after JCAR014
Group 1 Dose Level 2 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
.
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
Secondary
Rate of Partial Response (PR) by Investigator Assessment Using Lugano Criteria
This outcome is a count of participants who experienced a best response of partial response (PR) by investigator assessment using Lugano criteria. 1 patient in Group 1 Early Dose Level 2 could not be analyzed for the outcome because they expired before their first response assessment.
Posted
Count of Participants
Participants
Up to 1 year
ID
Title
Description
OG000
Group I (JCAR014, Durvalumab) Early - Dose Level 2
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - early: start durvalumab no earlier than 7 days after JCAR014.
Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG001
Group I (JCAR014, Durvalumab) Late- Dose Level 1
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - late: start durvalumab no earlier than 21 days after JCAR014
Group 1 Dose Level 2 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
.
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
Secondary
Objective Response Rate by Investigator Assessment Using Lugano Criteria
ORR, defined as a count of participant with a best response of either complete response or partial response. 1 patient in Group 1 Early Dose Level 2 could not be analyzed for the outcome because they expired before their first response assessment.
Posted
Count of Participants
Participants
Up to 1 year
ID
Title
Description
OG000
Group I (JCAR014, Durvalumab) Early - Dose Level 2
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - early: start durvalumab no earlier than 7 days after JCAR014.
Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG001
Group I (JCAR014, Durvalumab) Late- Dose Level 1
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - late: start durvalumab no earlier than 21 days after JCAR014
Group 1 Dose Level 2 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
.
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
Secondary
Duration of Response
Duration of response will be an average amount of days from first response assessment until progression or death for treated patients. Total number analyzed will be the patients that progressed or died, excluding those that did not progress or die. 1 patient in Group 1 Early Dose Level 2 could not be analyzed for the outcome because they expired before their first response assessment.
Total number analyzed will be the patients that progressed or died, excluding those that did not progress or die. 1 patient in Group 1 Early Dose Level 2 could not be analyzed for the outcome because they expired before their first response assessment.
Posted
Mean
Full Range
days
From first response to progressive disease or death, assessed up to 1 year
ID
Title
Description
OG000
Group I (JCAR014, Durvalumab) Early - Dose Level 2
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - early: start durvalumab no earlier than 7 days after JCAR014.
Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG001
Group I (JCAR014, Durvalumab) Late- Dose Level 1
Secondary
Progression Free Survival
Outcome will be reported as a count of those who did not progress and did not die while on study.
Posted
Count of Participants
Participants
From date of first study treatment to progressive disease or death, assessed up to 1 year
ID
Title
Description
OG000
Group I (JCAR014, Durvalumab) Early - Dose Level 2
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - early: start durvalumab no earlier than 7 days after JCAR014.
Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG001
Group I (JCAR014, Durvalumab) Late- Dose Level 1
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - late: start durvalumab no earlier than 21 days after JCAR014
Group 1 Dose Level 2 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
.
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
Secondary
Overall Survival
Outcome will be reported as a count of participants who survived while on study. Survival was assessed up to 1 year.
Posted
Count of Participants
Participants
From date of first study treatment to death, assessed up to 1 year
ID
Title
Description
OG000
Group I (JCAR014, Durvalumab) Early - Dose Level 2
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - early: start durvalumab no earlier than 7 days after JCAR014.
Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG001
Group I (JCAR014, Durvalumab) Late- Dose Level 1
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - late: start durvalumab no earlier than 21 days after JCAR014
Group 1 Dose Level 2 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
.
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
Other Pre-specified
B-cell Depletion in Circulation, Profile of Soluble Circulating Proteins Such as Cytokines and Chemokines, and Changes in the Level of Detectable Soluble PD-L1
Not Posted
Up to 12 months
Participants
Other Pre-specified
Change in the Phenotype of Tumor Cells (e.g., Expression of PD-L1) and of the Tumor Microenvironment (e.g., Infiltration by Chimeric Antigen Receptor [CAR] T Cells)
Flow cytometry may be used in the blood, bone marrow, and cerebrospinal fluid (CSF) (if applicable).
Not Posted
Baseline up to 12 months
Participants
Other Pre-specified
Phenotype and/or Genetic Profile of Endogenous Immune Cells and CAR T Cells
Flow cytometry may be used in the blood, bone marrow, and CSF (if applicable).
Not Posted
Up to 12 months
Participants
Other Pre-specified
Cmax of Durvalumab in Serum
Not Posted
Up to 12 months
Participants
Other Pre-specified
AUC of Durvalumab in Serum
Not Posted
Up to 12 months
Participants
Other Pre-specified
Clearance of Durvalumab in Serum
Not Posted
Up to 12 months
Participants
Other Pre-specified
Terminal Half-life of Durvalumab in Serum
Not Posted
Up to 12 months
Participants
Other Pre-specified
Antibodies and Cellular Immune Responses to JCAR014
Cellular immune responses to JCAR014 will be considered in patients who have two consecutive negative assays for JCAR014 or who have recovered endogenous B cells. Cellular responses to JCAR014 will be evaluated by assessing reactivity of patient peripheral T cells to JCAR014. Peripheral blood will be collected for these studies.
Not Posted
Up to 12 months
Participants
Other Pre-specified
Anti-drug Antibodies Directed Against Durvalumab
Will be assessed using a validated immunoassay in serum samples.
Not Posted
Up to 12 months
Participants
Time Frame
28 days post last infusion of Durvalumab, up to 1 year
Description
An adverse event (AE) is the development of any untoward medical occurrence or the clinical deterioration of a pre-existing medical condition in a patient or clinical study patient administered a medicinal product (e.g., JCAR014 and/or durvalumab). Reporting of AEs will be based on the Medical Dictionary for Regulatory Activities (MedDRA) and CTCAE version 4.03.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Group I (JCAR014, Durvalumab) Early - Dose Level 2
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - early: start durvalumab no earlier than 7 days after JCAR014.
Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
3
5
4
5
5
5
EG001
Group I (JCAR014, Durvalumab) Late - Dose Level 1
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - late: start durvalumab no earlier than 21 days after JCAR014
Group 1 Dose Level 2 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
2
3
3
3
3
3
EG002
Group I (JCAR014, Durvalumab) Late - Dose Level 2
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - late: start durvalumab no earlier than 21 days after JCAR014
Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
0
3
2
3
3
3
EG003
Group II (Durvalumab, JCAR014) - Dose Level 1
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
1
1
1
1
1
1
EG004
Group II (Durvalumab, JCAR014) - Dose Level 2
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
0
1
0
1
1
1
EG005
Group II (Durvalumab, JCAR014) - Dose Level 3
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells
0
3
2
3
3
3
EG006
Group II (Durvalumab, JCAR014) - Dose Level 4
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
3
6
4
6
6
6
EG007
Group II (Durvalumab, JCAR014) - Dose Level 5
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
4
7
4
7
7
7
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
FEBRILE NEUTROPENIA
Blood and lymphatic system disorders
Systematic Assessment
EG0001 events1 affected5 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG0030 events0 affected1 at risk
EG0040 events0 affected1 at risk
EG0050 events0 affected3 at risk
EG0060 events0 affected6 at risk
EG0072 events2 affected7 at risk
SINUS TACHYCARDIA
Cardiac disorders
Systematic Assessment
EG0001 events1 affected5 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
ABDOMINAL PAIN
Gastrointestinal disorders
Systematic Assessment
EG0000 events0 affected5 at risk
EG0012 events2 affected3 at risk
EG0020 events0 affected3 at risk
EG003
DUODENAL HEMORRHAGE
Gastrointestinal disorders
Systematic Assessment
EG0000 events0 affected5 at risk
EG0012 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
DEATH NOS
General disorders
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
FEVER
General disorders
Systematic Assessment
EG0001 events1 affected5 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
MULTI-ORGAN FAILURE
General disorders
Systematic Assessment
EG0001 events1 affected5 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
BILE DUCT STENOSIS
Hepatobiliary disorders
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
CYTOKINE RELEASE SYNDROME
Immune system disorders
Systematic Assessment
EG0002 events2 affected5 at risk
EG0011 events1 affected3 at risk
EG0021 events1 affected3 at risk
EG003
BACTEREMIA
Infections and infestations
Systematic Assessment
EG0001 events1 affected5 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
INFECTIONS AND INFESTATIONS - OTHER, SPECIFY: CENTRAL LINE INFECTION
Infections and infestations
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
INFECTIONS AND INFESTATIONS - OTHER, SPECIFY: COAG NEGATIVE STAPHYLOCOCCUS BACTEREMIA
Infections and infestations
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
INFECTIONS AND INFESTATIONS - OTHER,SPECIFY: PARAINFLUENZAE VIRUS INFECTION
Infections and infestations
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
SEPSIS
Infections and infestations
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
ANOREXIA
Metabolism and nutrition disorders
Systematic Assessment
EG0001 events1 affected5 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
TUMOR PAIN
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
ENCEPHALOPATHY
Nervous system disorders
Systematic Assessment
EG0001 events1 affected5 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
SOMNOLENCE
Nervous system disorders
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
HEMATURIA
Renal and urinary disorders
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
DYSPNEA
Respiratory, thoracic and mediastinal disorders
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
PLEURAL EFFUSION
Respiratory, thoracic and mediastinal disorders
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
HYPOTENSION
Vascular disorders
Systematic Assessment
EG0002 events1 affected5 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
ANEMIA
Blood and lymphatic system disorders
Systematic Assessment
EG0002 events2 affected5 at risk
EG00110 events2 affected3 at risk
EG0025 events3 affected3 at risk
EG0031 events1 affected1 at risk
EG0041 events1 affected1 at risk
EG0051 events1 affected3 at risk
EG00610 events4 affected6 at risk
EG00712 events4 affected7 at risk
INVESTIGATIONS - OTHER, SPECIFY: INCREASED NUCLEATED RED BLOOD CELLS
Blood and lymphatic system disorders
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
ATRIAL FIBRILLATION
Cardiac disorders
Systematic Assessment
EG0002 events1 affected5 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
PALPITATIONS
Cardiac disorders
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
SINUS BRADYCARDIA
Cardiac disorders
Systematic Assessment
EG0001 events1 affected5 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
SINUS TACHYCARDIA
Cardiac disorders
Systematic Assessment
EG0004 events3 affected5 at risk
EG00127 events2 affected3 at risk
EG0023 events2 affected3 at risk
EG003
SINUS TACHYCARDIA (INTERMITTENT)
Cardiac disorders
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
SINUS TACHYCARDIA, INTERMITTENT
Cardiac disorders
Systematic Assessment
EG0000 events0 affected5 at risk
EG0010 events0 affected3 at risk
EG0022 events1 affected3 at risk
EG003
TACHYCARDIA
Cardiac disorders
Systematic Assessment
EG0001 events1 affected5 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
VENTRICULAR ARRHYTHMIA
Cardiac disorders
Systematic Assessment
EG0000 events0 affected5 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
EAR AND LABYRINTH DISORDERS - OTHER, SPECIFY: CERUMEN IMPACTION
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - late: start durvalumab no earlier than 21 days after JCAR014
Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG003
Group II (Durvalumab, JCAR014) - Dose Level 1
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG004
Group II (Durvalumab, JCAR014) - Dose Level 2
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG005
Group II (Durvalumab, JCAR014) - Dose Level 3
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG006
Group II (Durvalumab, JCAR014) - Dose Level 4
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG007
Group II (Durvalumab, JCAR014) - Dose Level 5
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
Units
Counts
Participants
OG0005
OG0013
OG0023
OG0031
OG0041
OG0053
OG0066
OG0077
Title
Denominators
Categories
Title
Measurements
OG0001
OG0010
OG0020
OG0030
OG0040
OG0050
OG0061
OG0071
Title
Denominators
Categories
Title
Measurements
OG000750
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
OG003
Group II (Durvalumab, JCAR014) - Dose Level 2
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
OG004
Group II (Durvalumab, JCAR014) - Dose Level 3
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells
OG005
Group II (Durvalumab, JCAR014) - Dose Level 4
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
OG006
Group II (Durvalumab, JCAR014) - Dose Level 5
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
Units
Counts
Participants
OG0003
OG0018
OG0021
OG0031
OG0043
OG0056
OG0066
Title
Denominators
Categories
Title
Measurements
OG000201.21(9.86 to 555.77)
OG00113.71(1.88 to 36.51)
OG0028.27(8.27 to 8.27)
OG0033.01(3.01 to 3.01)
OG00413.15(3.51 to 32.10)
OG00518.13(5.16 to 51.49)
OG0067.53(1.44 to 13.83)
OG002
Group II (Durvalumab, JCAR014) - Dose Level 1
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
OG003
Group II (Durvalumab, JCAR014) - Dose Level 2
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
OG004
Group II (Durvalumab, JCAR014) - Dose Level 3
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells
OG005
Group II (Durvalumab, JCAR014) - Dose Level 4
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
OG006
Group II (Durvalumab, JCAR014) - Dose Level 5
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
Units
Counts
Participants
OG0003
OG0018
OG0021
OG0031
OG0043
OG0056
OG0066
Title
Denominators
Categories
Title
Measurements
OG000844.77(105.13 to 2078.77)
OG001104.33(10.01 to 316.62)
OG00247.96(47.96 to 47.96)
OG00332.44(32.44 to 32.44)
OG00490.78(23.13 to 220.87)
OG005160.94(54.43 to 330.53)
OG00671.97(14.39 to 162.37)
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
OG003
Group II (Durvalumab, JCAR014) - Dose Level 2
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
OG004
Group II (Durvalumab, JCAR014) - Dose Level 3
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells
OG005
Group II (Durvalumab, JCAR014) - Dose Level 4
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
OG006
Group II (Durvalumab, JCAR014) - Dose Level 5
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
Units
Counts
Participants
OG0003
OG0018
OG0021
OG0031
OG0043
OG0056
OG0066
Title
Denominators
Categories
Title
Measurements
OG00037647.95(3699.84 to 97951.33)
OG00110043.68(1717.18 to 25286.16)
OG0023690.24(3690.24 to 3690.24)
OG0031949.22(1949.22 to 1949.22)
OG0048295.36(1120.19 to 20755.61)
OG00527841.31(1927.33 to 87193.83)
OG00626297.43(1515.33 to 122322.41)
OG002
Group II (Durvalumab, JCAR014) - Dose Level 1
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
OG003
Group II (Durvalumab, JCAR014) - Dose Level 2
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
OG004
Group II (Durvalumab, JCAR014) - Dose Level 3
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells
OG005
Group II (Durvalumab, JCAR014) - Dose Level 4
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
OG006
Group II (Durvalumab, JCAR014) - Dose Level 5
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
Units
Counts
Participants
OG0003
OG0018
OG0021
OG0031
OG0043
OG0056
OG0067
Title
Denominators
Categories
Title
Measurements
OG000296188.95(40685.13 to 730201.08)
OG001104088.38(19729.18 to 433057.46)
OG00218710.77(18710.77 to 18710.77)
OG00316721.68(16721.68 to 16721.68)
OG00463778.63(11246.81 to 155355.19)
OG005353471.10(27198.84 to 1266668.39)
OG006389065.24(14387.21 to 1811692.73)
Group II (Durvalumab, JCAR014) - Dose Level 1
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
OG003
Group II (Durvalumab, JCAR014) - Dose Level 2
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
OG004
Group II (Durvalumab, JCAR014) - Dose Level 3
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells
OG005
Group II (Durvalumab, JCAR014) - Dose Level 4
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
OG006
Group II (Durvalumab, JCAR014) - Dose Level 5
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
Units
Counts
Participants
OG0002
OG0013
OG0021
OG0030
OG0043
OG0052
OG0062
Title
Denominators
Categories
Title
Measurements
OG000113(91 to 134)
OG001191(49 to 392)
OG00228(28 to 28)
OG004199(168 to 227)
OG005183(149 to 217)
OG00664(39 to 88)
OG002
Group I (JCAR014, Durvalumab) Late - Dose Level 2
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - late: start durvalumab no earlier than 21 days after JCAR014
Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG003
Group II (Durvalumab, JCAR014) - Dose Level 1
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG004
Group II (Durvalumab, JCAR014) - Dose Level 2
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG005
Group II (Durvalumab, JCAR014) - Dose Level 3
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG006
Group II (Durvalumab, JCAR014) - Dose Level 4
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG007
Group II (Durvalumab, JCAR014) - Dose Level 5
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
Units
Counts
Participants
OG0004
OG0013
OG0023
OG0031
OG0041
OG0053
OG0066
OG0077
Title
Denominators
Categories
Title
Measurements
OG0001
OG0011
OG0022
OG0030
OG0041
OG0052
OG0062
OG0071
OG002
Group I (JCAR014, Durvalumab) Late - Dose Level 2
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - late: start durvalumab no earlier than 21 days after JCAR014
Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG003
Group II (Durvalumab, JCAR014) - Dose Level 1
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG004
Group II (Durvalumab, JCAR014) - Dose Level 2
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG005
Group II (Durvalumab, JCAR014) - Dose Level 3
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG006
Group II (Durvalumab, JCAR014) - Dose Level 4
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG007
Group II (Durvalumab, JCAR014) - Dose Level 5
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
Units
Counts
Participants
OG0004
OG0013
OG0023
OG0031
OG0041
OG0053
OG0066
OG0077
Title
Denominators
Categories
Title
Measurements
OG0001
OG0010
OG0021
OG0030
OG0041
OG0050
OG0060
OG0071
OG002
Group I (JCAR014, Durvalumab) Late - Dose Level 2
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - late: start durvalumab no earlier than 21 days after JCAR014
Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG003
Group II (Durvalumab, JCAR014) - Dose Level 1
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG004
Group II (Durvalumab, JCAR014) - Dose Level 2
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG005
Group II (Durvalumab, JCAR014) - Dose Level 3
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG006
Group II (Durvalumab, JCAR014) - Dose Level 4
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG007
Group II (Durvalumab, JCAR014) - Dose Level 5
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
Units
Counts
Participants
OG0004
OG0013
OG0023
OG0031
OG0041
OG0053
OG0066
OG0077
Title
Denominators
Categories
Title
Measurements
OG0001
OG0011
OG0022
OG0030
OG0041
OG0052
OG0062
OG0072
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - late: start durvalumab no earlier than 21 days after JCAR014
Group 1 Dose Level 2 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
.
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG002
Group I (JCAR014, Durvalumab) Late - Dose Level 2
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - late: start durvalumab no earlier than 21 days after JCAR014
Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG003
Group II (Durvalumab, JCAR014) - Dose Level 1
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG004
Group II (Durvalumab, JCAR014) - Dose Level 2
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG005
Group II (Durvalumab, JCAR014) - Dose Level 3
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG006
Group II (Durvalumab, JCAR014) - Dose Level 4
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG007
Group II (Durvalumab, JCAR014) - Dose Level 5
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
Units
Counts
Participants
OG0002
OG0012
OG0022
OG0030
OG0041
OG0051
OG0064
OG0077
Title
Denominators
Categories
Title
Measurements
OG00072.5(0 to 145)
OG00147.5(0 to 95)
OG00242(0 to 84)
OG00435(35 to 35)
OG00531(31 to 31)
OG00697.75(0 to 357)
OG00718.14(0 to 99)
OG002
Group I (JCAR014, Durvalumab) Late - Dose Level 2
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - late: start durvalumab no earlier than 21 days after JCAR014
Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG003
Group II (Durvalumab, JCAR014) - Dose Level 1
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG004
Group II (Durvalumab, JCAR014) - Dose Level 2
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG005
Group II (Durvalumab, JCAR014) - Dose Level 3
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG006
Group II (Durvalumab, JCAR014) - Dose Level 4
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG007
Group II (Durvalumab, JCAR014) - Dose Level 5
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
Units
Counts
Participants
OG0005
OG0013
OG0023
OG0031
OG0041
OG0053
OG0066
OG0077
Title
Denominators
Categories
Title
Measurements
OG0002
OG0011
OG0021
OG0030
OG0040
OG0052
OG0062
OG0070
OG002
Group I (JCAR014, Durvalumab) Late - Dose Level 2
Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
Group 1 - late: start durvalumab no earlier than 21 days after JCAR014
Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG003
Group II (Durvalumab, JCAR014) - Dose Level 1
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG004
Group II (Durvalumab, JCAR014) - Dose Level 2
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG005
Group II (Durvalumab, JCAR014) - Dose Level 3
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG006
Group II (Durvalumab, JCAR014) - Dose Level 4
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV
Cyclophosphamide: Given IV
Durvalumab: Given IV
Fludarabine: Given IV
OG007
Group II (Durvalumab, JCAR014) - Dose Level 5
Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV