Cytokine Release Syndrome, Neurotoxicity, Neurotoxicity Syndromes, Non Hodgkin Lymphoma, Refractory Non-Hodgkin Lymphoma, Relapsed Non Hodgkin Lymphoma
Conditions
Keywords
Non Hodgkin Lymphoma, Refractory Non-Hodgkin Lymphoma, Relapsed Non Hodgkin Lymphoma, Neurotoxicity, Neurotoxicity Syndromes, Cytokine Release Syndrome
Brief summary
This research study is studying the combination of anakinra and axicabtagene ciloleucel to reduce the occurrence of the side effects Cytokine Release Syndrome (CRS) and neurologic toxicities with relapsed or refractory Non-Hodgkin lymphoma (NHL). * Relapsed NHL is the condition of returned Non-Hodgkin lymphoma. * Refractory NHL is the condition of previous treatment resistant Non-Hodgkin lymphoma. * Cytokine Release Syndrome (CRS) is a group of side effect symptoms that can include nausea, headache, rapid heartbeat, shortness of breath, kidney damage, and rash. * Neurologic toxicity is nervous system disorder characterized by confusion This research study involves two drugs: * Anakinra * Axicabtagene Ciloleucel.
Detailed description
This Phase 2, single center, open-label research study is studying the combination of Anakinra and Axicabtagene Ciloleucel to reduce the occurrence of the side effects Cytokine Release Syndrome (CRS) and neurologic toxicities in people with relapsed or refractory Non-Hodgkin lymphoma (NHL). The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. * This research study involves two drugs: * Anakinra * Axicabtagene Ciloleucel * A total of 20 participants are anticipated to be enrolled to this trial * The U.S. Food and Drug Administration (FDA) has not approved anakinra for use in treatment of Non-Hodgkin lymphoma (NHL).
Interventions
DRUGAnakinra
Subcutaneous, dosage per protocol. Day 0 through Day 6.
DRUGAxicabtagene Ciloleucel
Once, intravenous infusion, dosage per protocol
Sponsors
Kite, A Gilead Company
Marcela V. Maus, M.D.,Ph.D.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. * At least 1 measurable lesion according to the revised IWG Response Criteria for Malignant Lymphoma 1. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy * At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy however steroids only require a 7-day washout. At least 3 half-lives must have elapsed from any prior systemic inhibitory/stimulatory immune checkpoint molecule therapy at the time the subject is planned for leukapheresis (e.g. ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists, etc). * Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for clinically non-significant toxicities such as alopecia) * Age 18 or older * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * ANC ≥1000/uL * Platelet count ≥75,000/uL * Absolute lymphocyte count ≥100/uL * Adequate renal, hepatic, pulmonary and cardiac function defined as: * Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min * Serum ALT/AST ≤2.5 ULN * Total bilirubin ≤1.5 mg/dl, except in subjects with Gilbert's syndrome. * Cardiac ejection fraction ≥ 50%, no clinically significant pericardial effusion, and no clinically significant ECG findings * No clinically significant pleural effusion * Baseline oxygen saturation \>92% on room air * Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential) Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
* History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) or follicular lymphoma unless disease free for at least 3 years * History of Richter's transformation of CLL * Autologous stem cell transplant within 6 weeks of planned axicabtagene ciloleucel infusion * History of allogeneic stem cell transplantation * Prior CD19 targeted therapy with the exception of subjects who received axicabtagene ciloleucel in this study and are eligible for re-treatment * Prior chimeric antigen receptor therapy or other genetically modified T cell therapy * History of severe, immediate hypersensitivity reaction attributed to aminoglycosides * Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. * History of HIV infection or acute or chronic active hepatitis B or C infection. Subjects with history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing per current Infectious Diseases Society of America (IDSA) guidelines. * Presence of any indwelling line or drain (e.g., percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter). Dedicated central venous access catheters such as a Port-a-Cath or Hickman catheter are permitted * Subjects with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of CNS lymphoma or primary CNS lymphoma, cerebrospinal fluid malignant cells or brain metastases * History or presence of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement * Subjects with cardiac atrial or cardiac ventricular lymphoma involvement * History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment * Expected or possible requirement for urgent therapy within 6 weeks due to ongoing or impending oncologic emergency (eg, tumor mass effect, tumor lysis syndrome) * Primary immunodeficiency * History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment * Any medical condition likely to interfere with assessment of safety or efficacy of study treatment * History of severe immediate hypersensitivity reaction to any of the agents used in this study * Live vaccine ≤ 6 weeks prior to planned start of conditioning regimen * Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. Females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential * Subjects of both genders who are not willing to practice birth control from the time of consent through 6 months after the completion of axicabtagene ciloleucel * In the investigators judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation * History of autoimmune disease (e.g. Crohn's, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Neurotoxicity as Per CTCAE v4.03 Criteria | 30 Days | The incidence of grade 2+ neurotoxicity is reported below and was assessed using CTCAE (Common Terminology Criteria for Adverse Events) v4.04 criteria. Neurotoxicity is a serious side effect of cancer treatments that can impact the central and peripheral nervous systems. Neurotoxicity manifestations vary and can include confusion, obtundation, seizures, hallucinations, aphasia, ataxia, and more rarely, profound cerebral edema. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | first objective response to disease progression death regardless of cause up 24 Months | Among participants who experience an objective response, duration of response (DOR) is defined as the date of their first objective response to disease progression per the revised IWG Response Criteria for Malignant Lymphoma, or death regardless of cause. Participants not meeting the criteria for progressive disease (PD) or death by the analysis data cutoff date will be censored at their last evaluable disease assessment date and their response will be noted as ongoing. \* PD = ≥ 50% increase from nadir in the sum of the products of at least two lymph nodes; ≥ 50% increase in product of the diameters of single node; new lesion \>1.5 cm; ≥ 50% size increase of splenic/hepatic nodules; ≥ 50% increase in longest diameter of any single previously identified node more than 1 cm in its short axis; PET scan positive |
| Progression-free Survival | infusion date to the date of disease progression or death from any cause up 24 Months | Kaplan-Meier estimates and 2-sided 95% confidence intervals will be generated for progression-free survival time |
| Objective Response Rate | 24 Months | Objective response rate (ORR) is defined as the incidence of either a complete response (CR) or a partial response (PR) by the revised IWG Response Criteria for Malignant Lymphoma. All participants who don't meet the ORR criteria by the analysis data cutoff date will be considered non-responders. * CR = complete disappearance of all detectable clinical evidence of disease and disease related symptoms if present before therapy; PET scan negative; lymph nodes/nodal masses regressed to normal size; normal size spleen/liver on CT scan; bone marrow aspirate and biopsy shows no evidence of disease by morphology or negative by IHC. * PR = ≥ 50% decrease in sum of the product of diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses; no size increase of nodes/liver/spleen; no new sites of disease; post-treatment PET scan positive in ≥ 1 previously involved site. |
| Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher | 24 Months | Subject incidence rates of adverse events including all, serious, fatal, CTCAE version 4.03 Grade 3 or higher and treatment related AEs reported throughout the conduct of the study will be tabulated by preferred term and system organ class |
| Rate of Cytokine Release Syndrome (CRS) as Per Lee 2014 for CRS | Within 30 days after infusion | The incidence of max grade 2+ CRS will be assessed |
| Overall Survival | time from axicabtagene ciloleucel infusion to the date of death or analysis data cutoff date will be censored at last contact date up to 24 months. | Kaplan-Meier estimates and 2-sided 95% confidence intervals will be generated for OS. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Anakinra and Axicabtagene Ciloleucel Patients who meet eligibility criteria for the study will subsequently be enrolled for treatment.
* Screening
* Enrollment/Leukapheresis period
* Bridging therapy (if applicable)
* Lymphodepleting chemotherapy period
* Investigational Product (IP) treatment period
* Anakinra
* Axicabtagene Ciloleucel
* Post treatment assessment period
* Long term follow-up period
Anakinra: Subcutaneous, dosage per protocol. Day 0 through Day 13.
Axicabtagene Ciloleucel: Once, intravenous infusion, dosage per protocol | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Anakinra and Axicabtagene Ciloleucel |
|---|---|
| Age, Continuous | 64 years STANDARD_DEVIATION 9.33 |
| Eastern Cooperative Oncology Group Grade 0 | 5 Participants |
| Eastern Cooperative Oncology Group Grade 1 | 10 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Histology DLBCL NOS | 9 Participants |
| Histology HGBCL | 1 Participants |
| Histology tFL | 5 Participants |
| International Prognostic Index | 3 Score (0-5) |
| Number of prior regimens Primary refractory disease | 3 Participants |
| Number of prior regimens Prior autologous HSCT | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 8 Participants |
| Tumor burden, Baseline LDH (U/L) | 223 U/L |
| Tumor burden, Baseline SPD (mm2) | 2239 mm2 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 7 / 15 |
| other Total, other adverse events | 15 / 15 |
| serious Total, serious adverse events | 9 / 15 |
Outcome results
Primary
Rate of Neurotoxicity as Per CTCAE v4.03 Criteria
The incidence of grade 2+ neurotoxicity is reported below and was assessed using CTCAE (Common Terminology Criteria for Adverse Events) v4.04 criteria. Neurotoxicity is a serious side effect of cancer treatments that can impact the central and peripheral nervous systems. Neurotoxicity manifestations vary and can include confusion, obtundation, seizures, hallucinations, aphasia, ataxia, and more rarely, profound cerebral edema.
Time frame: 30 Days
Population: Neurotoxicity, Max Grade
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Anakinra and Axicabtagene Ciloleucel | Rate of Neurotoxicity as Per CTCAE v4.03 Criteria | Grade 1 | 3 Participants |
| Anakinra and Axicabtagene Ciloleucel | Rate of Neurotoxicity as Per CTCAE v4.03 Criteria | Grade 2 | 2 Participants |
| Anakinra and Axicabtagene Ciloleucel | Rate of Neurotoxicity as Per CTCAE v4.03 Criteria | Grade 3-4 | 5 Participants |
| Anakinra and Axicabtagene Ciloleucel | Rate of Neurotoxicity as Per CTCAE v4.03 Criteria | Grade 5 | 1 Participants |
| Anakinra and Axicabtagene Ciloleucel | Rate of Neurotoxicity as Per CTCAE v4.03 Criteria | Did not experience Neurotoxicity | 4 Participants |
Secondary
Duration of Response
Among participants who experience an objective response, duration of response (DOR) is defined as the date of their first objective response to disease progression per the revised IWG Response Criteria for Malignant Lymphoma, or death regardless of cause. Participants not meeting the criteria for progressive disease (PD) or death by the analysis data cutoff date will be censored at their last evaluable disease assessment date and their response will be noted as ongoing. \* PD = ≥ 50% increase from nadir in the sum of the products of at least two lymph nodes; ≥ 50% increase in product of the diameters of single node; new lesion \>1.5 cm; ≥ 50% size increase of splenic/hepatic nodules; ≥ 50% increase in longest diameter of any single previously identified node more than 1 cm in its short axis; PET scan positive
Time frame: first objective response to disease progression death regardless of cause up 24 Months
Population: Progression Free Survival (PFS); Overall Survival OS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anakinra and Axicabtagene Ciloleucel | Duration of Response | PFS at 12 months | 42.4 percentage of participants |
| Anakinra and Axicabtagene Ciloleucel | Duration of Response | OS at 6 months | 79.4 percentage of participants |
| Anakinra and Axicabtagene Ciloleucel | Duration of Response | OS at 12 months | 64.2 percentage of participants |
| Anakinra and Axicabtagene Ciloleucel | Duration of Response | PFS at 6 months | 58.2 percentage of participants |
Secondary
Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher
Subject incidence rates of adverse events including all, serious, fatal, CTCAE version 4.03 Grade 3 or higher and treatment related AEs reported throughout the conduct of the study will be tabulated by preferred term and system organ class
Time frame: 24 Months
Population: Participants who experienced Adverse Events (AE), Grade 3 or higher
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Anakinra and Axicabtagene Ciloleucel | Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher | Infections and Infestations: Grade 3 | 4 Participants |
| Anakinra and Axicabtagene Ciloleucel | Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher | Nervous System Disorders : Grade 4 | 1 Participants |
| Anakinra and Axicabtagene Ciloleucel | Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher | Blood and lymphatic system disorders : Grade 3 | 9 Participants |
| Anakinra and Axicabtagene Ciloleucel | Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher | Blood and lymphatic system disorders : Grade 4 | 1 Participants |
| Anakinra and Axicabtagene Ciloleucel | Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher | Cardiac disorders : Grade 3 | 1 Participants |
| Anakinra and Axicabtagene Ciloleucel | Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher | Gastrointestinal disorders : Grade 3 | 4 Participants |
| Anakinra and Axicabtagene Ciloleucel | Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher | General disorders and administration site conditions : Grade 3 | 5 Participants |
| Anakinra and Axicabtagene Ciloleucel | Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher | Hepatobiliary disorders : Grade 3 | 1 Participants |
| Anakinra and Axicabtagene Ciloleucel | Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher | Immune system disorders : Grade 3 | 1 Participants |
| Anakinra and Axicabtagene Ciloleucel | Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher | Investigations : Grade 3 | 9 Participants |
| Anakinra and Axicabtagene Ciloleucel | Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher | Investigations : Grade 4 | 9 Participants |
| Anakinra and Axicabtagene Ciloleucel | Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher | Psychiatric disorders : Grade 3 | 2 Participants |
| Anakinra and Axicabtagene Ciloleucel | Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher | Renal and urinary disorders : Grade 3 | 2 Participants |
| Anakinra and Axicabtagene Ciloleucel | Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher | Infections and Infestations : Grade 4 | 1 Participants |
| Anakinra and Axicabtagene Ciloleucel | Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher | Infections and Infestations : Grade 5 | 1 Participants |
| Anakinra and Axicabtagene Ciloleucel | Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher | Nervous System Disorders : Grade 3 | 6 Participants |
| Anakinra and Axicabtagene Ciloleucel | Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher | Ear and labyrinth disorders : Grade 3 | 1 Participants |
| Anakinra and Axicabtagene Ciloleucel | Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher | Endocrine disorders : Grade 3 | 1 Participants |
| Anakinra and Axicabtagene Ciloleucel | Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher | Endocrine disorders : Grade 4 | 1 Participants |
| Anakinra and Axicabtagene Ciloleucel | Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher | Metabolism and nutrition disorders : Grade 3 | 9 Participants |
| Anakinra and Axicabtagene Ciloleucel | Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher | Metabolism and nutrition disorders : Grade 4 | 1 Participants |
| Anakinra and Axicabtagene Ciloleucel | Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher | Musculoskeletal and connective tissue disorders : Grade 3 | 2 Participants |
| Anakinra and Axicabtagene Ciloleucel | Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher | Respiratory, thoracic and mediastinal disorders : Grade 3 | 5 Participants |
| Anakinra and Axicabtagene Ciloleucel | Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher | Vascular disorders : Grade 3 | 4 Participants |
| Anakinra and Axicabtagene Ciloleucel | Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher | Vascular disorders : Grade 4 | 1 Participants |
Secondary
Objective Response Rate
Objective response rate (ORR) is defined as the incidence of either a complete response (CR) or a partial response (PR) by the revised IWG Response Criteria for Malignant Lymphoma. All participants who don't meet the ORR criteria by the analysis data cutoff date will be considered non-responders. * CR = complete disappearance of all detectable clinical evidence of disease and disease related symptoms if present before therapy; PET scan negative; lymph nodes/nodal masses regressed to normal size; normal size spleen/liver on CT scan; bone marrow aspirate and biopsy shows no evidence of disease by morphology or negative by IHC. * PR = ≥ 50% decrease in sum of the product of diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses; no size increase of nodes/liver/spleen; no new sites of disease; post-treatment PET scan positive in ≥ 1 previously involved site.
Time frame: 24 Months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Anakinra and Axicabtagene Ciloleucel | Objective Response Rate | Overall Response Rate | 13 Participants |
| Anakinra and Axicabtagene Ciloleucel | Objective Response Rate | Complete Response | 7 Participants |
| Anakinra and Axicabtagene Ciloleucel | Objective Response Rate | Partial Response | 6 Participants |
Secondary
Overall Survival
Kaplan-Meier estimates and 2-sided 95% confidence intervals will be generated for OS.
Time frame: time from axicabtagene ciloleucel infusion to the date of death or analysis data cutoff date will be censored at last contact date up to 24 months.
Population: Overall Survival
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anakinra and Axicabtagene Ciloleucel | Overall Survival | OS at 6 months | 79.4 percentage of participants |
| Anakinra and Axicabtagene Ciloleucel | Overall Survival | OS at 12 months | 64.2 percentage of participants |
Secondary
Progression-free Survival
Kaplan-Meier estimates and 2-sided 95% confidence intervals will be generated for progression-free survival time
Time frame: infusion date to the date of disease progression or death from any cause up 24 Months
Population: Progression Free Survival
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anakinra and Axicabtagene Ciloleucel | Progression-free Survival | PFS at 6 months | 58.2 percentage of participants |
| Anakinra and Axicabtagene Ciloleucel | Progression-free Survival | PFS at 12 months | 42.4 percentage of participants |
Secondary
Rate of Cytokine Release Syndrome (CRS) as Per Lee 2014 for CRS
The incidence of max grade 2+ CRS will be assessed
Time frame: Within 30 days after infusion
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Anakinra and Axicabtagene Ciloleucel | Rate of Cytokine Release Syndrome (CRS) as Per Lee 2014 for CRS | Grade 4 | 1 Participants |
| Anakinra and Axicabtagene Ciloleucel | Rate of Cytokine Release Syndrome (CRS) as Per Lee 2014 for CRS | Grade 1 | 6 Participants |
| Anakinra and Axicabtagene Ciloleucel | Rate of Cytokine Release Syndrome (CRS) as Per Lee 2014 for CRS | No CRS | 1 Participants |
| Anakinra and Axicabtagene Ciloleucel | Rate of Cytokine Release Syndrome (CRS) as Per Lee 2014 for CRS | Grade 2 | 6 Participants |
| Anakinra and Axicabtagene Ciloleucel | Rate of Cytokine Release Syndrome (CRS) as Per Lee 2014 for CRS | Grade 3 | 1 Participants |