Acute Myeloid Leukemia
Conditions
Brief summary
The goal of this clinical study is to learn more about the safety and dosing of the study drug, KITE-222, in participants with relapsed/refractory (r/r) acute myeloid leukemia (AML).
Interventions
DRUGCyclophosphamide
Administered intravenously
DRUGFludarabine
Administered intravenously
BIOLOGICALKITE-222
A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously
Sponsors
Kite, A Gilead Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Relapse/refractory (r/r) de novo or secondary acute myeloid leukemia (AML) * Morphological disease in the bone marrow and/or peripheral blood within 28 days before enrollment * Prior exposure to the relevant agent class for individuals with AML characterized by a mutation targeted by an approved therapy * Institutional criteria for allogeneic (allo) - stem cell transplant (SCT) fitness must be met: individuals must have an identified stem-cell donor readily available for potential allo-SCT after therapy with KITE-222 * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Adequate hematologic status, defined as: * Absolute neutrophil count (ANC) ≥ 1000/µL unless, in the opinion of the investigator, cytopenia is due to underlying leukemia * Platelet count ≥ 50,000/µL unless, in the opinion of the investigator, thrombocytopenia is due to underlying leukemia * Absolute lymphocyte count (ALC) ≥ 100/µL * Adequate renal, hepatic, pulmonary and cardiac function defined as: * Creatinine clearance (as estimated by the Cockcroft Gault formula) ≥ 60 mL/min * Serum alanine aminotransferase/aspartate aminotransferase ≤ 2.5 x upper limit of normal * Total bilirubin ≤ 1.5 mg/dL, except in individuals with Gilbert's syndrome * Cardiac ejection fraction ≥ 50%, no clinically significant pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings * Baseline oxygen saturation \> 92% on room air and no clinically significant pleural effusion as determined by chest imaging * Contraception: males and females of childbearing potential must agree to use an effective method of contraception * Pregnancy testing: females of childbearing potential must have a negative serum or urine pregnancy test Key
Exclusion criteria
* Diagnosis of acute promyelocytic leukemia * Auto-SCT within the 6 weeks before enrollment * Donor Lymphocyte Infusions (DLI) within 28 days prior to enrollment * Any drug used for graft-versus-host-disease (GVHD) within 4 weeks prior to enrollment * Acute GVHD grade II-IV by Mount Sinai Acute GVHD International Consortium criteria * Active central nervous system (CNS) disease involvement * Requirement for urgent therapy due to ongoing or impending oncologic emergency (eg, leukostasis or tumor lysis syndrome (TLS)) or the possible requirement for urgent therapy due to ongoing or impending oncologic emergency (eg, spinal cord compression, bowel obstruction, leukostasis, or TLS) at the time of enrollment or KITE-222 infusion * History of C-type lectin-like molecule-1 (CLL-1)-directed therapy or genetically modified T-cell therapy * History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg, cervix, bladder, or breast) unless disease free for at least 3 years after the last definitive therapy * History of severe hypersensitivity reaction to aminoglycosides * History of concomitant genetic syndrome associated with bone marrow failure * Individuals with a genetic syndrome that increases the risk of allo-SCT, including Down syndrome (trisomy 21) * History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, New York Heart Association Class II or greater congestive heart failure, atrial fibrillation, or other clinically significant cardiac disease within 12 months before enrollment * Individuals with cardiac atrial or ventricular leukemia involvement * History of symptomatic deep vein thrombosis (DVT) or a pulmonary embolism within 6 months of enrollment. History of upper extremity line related DVT within the 3 months of conditioning chemotherapy. * Primary immunodeficiency disorders * History of a human immunodeficiency virus (HIV) infection or acute or chronic active hepatitis B or C infection * History of an autoimmune disease resulting in end-organ injury or requiring systemic immunosuppression or systemic disease modifying agents within the last 2 years * History or presence of a CNS disorder * Presence or suspicion of a fungal, bacterial, viral, or other infection that is uncontrolled or requiring antimicrobials for management * Live vaccine received within the ≤ 4 weeks before enrollment, or anticipation of the need for a live vaccination during the course of the study * Inability to tolerate prophylactic antifungal and antibacterial therapy * Presence of any indwelling line or drain * Ongoing Grade 2 or higher toxicities from previous therapies, excluding hematologic toxicities * Females of childbearing potential who are pregnant or breastfeeding Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced Dose Limiting Toxicities (DLTs) | Up to 28 days | DLTs defined as KITE-222-related events with an onset within the first 28 days after the KITE-222 infusion:Grade(GR) 5 event,GR 4 cytokine release syndrome(CRS) or GR 3 CRS not improving to ≤ GR 2 by 72 hours,≥GR 3 cardiac and/or pulmonary event(Exceptions:related to CRS and improve to ≤GR 2 by 72 hours, managed by noninvasive care & resolves to baseline by Day28),GR 4 immune-effector cell-associated neurotoxicity syndrome(ICANS) or other GR 4 adverse events(AEs)associated to neurologic events,GR 3 ICANS(Exceptions: GR 3 ICANS based only on immune-effector cell-associated encephalopathy(ICE) score and/or depressed level of consciousness that improves to ≤GR 2 by 72 hours),≥GR 3 infusion or immediate hypersensitivity reaction,Ongoing GR 4 neutropenia or thrombocytopenia(not due to leukemia persistence)by Day 42 to who have not had conditioning regimen for allo-stem cell transplant,other KITE-222 related GR 3 non-hematologic AEs lasting \>7 days,KITE-222-related GR 4 non-hematologic AEs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Up to 3.2 months | Grading categories are determined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Grade 1: mild, Grade 2: moderate, Grade 3: severe or medically significant, Grade 4: life-threatening; Grade 5: Death related to AE. |
| Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Up to 3.2 months | Grading categories are determined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Grade 1: mild, Grade 2: moderate, Grade 3: severe or medically significant, Grade 4: life-threatening; Grade 5: Death related to AE. |
| Time to Neutrophil Recovery | Up to 3.2 months | Time to neutrophil recovery after KITE-222 infusion & before the start of the conditioning therapy for allo-SCT was calculated as the time from the date of KITE-222 infusion to the first day when neutrophils are 0.5 × 10\^9/liter (L), and as the time from the date of KITE-222 infusion to the first day when neutrophils are 1.0 × 10\^9/L. Per European Leukemia Net (ELN) 2017 classification, determined by study investigators, CR was defined as bone marrow (BM) blasts \<5%; absence of circulating blasts and blasts with Auer rods;absence of extramedullary disease;absolute neutrophil count (ANC) ≥1.0 × 10\^9/L (1000/microliter (μL));platelet count ≥100 × 10\^9/L (100000/μL). CRi was defined as all CR criteria except for residual neutropenia (\<1.0 × 10\^9/L \[1000/μL\]) or thrombocytopenia (\<100 × 10\^9/L \[100000/μL\]). |
| Time to Platelet Recovery | Up to 3.2 months | Time to platelet recovery after KITE-222 infusion and before the start of the conditioning therapy for subsequent allo-SCT was calculated as the time from the date of KITE-222 infusion to the first day when platelets are 50 × 10\^9/L, and the time from the date of KITE-222 infusion to the first day platelets are 100 × 10\^9/L. Per European Leukemia Net (ELN) 2017 classification, determined by study investigators, CR was defined as bone marrow (BM) blasts \<5%; absence of circulating blasts and blasts with Auer rods;absence of extramedullary disease;absolute neutrophil count (ANC) ≥1.0 × 10\^9/L (1000/microliter (μL));platelet count ≥100 × 10\^9/L (100000/μL). CRi was defined as all CR criteria except for residual neutropenia (\<1.0 × 10\^9/L \[1000/μL\]) or thrombocytopenia (\<100 × 10\^9/L \[100000/μL\]). |
| Composite Complete Remission (CCR) Rate | Up to 3.2 months | CCR rate=Percentage of participants who achieve complete remission (CR) + CR without measurable residual disease (CRMRD-) + CR with incomplete hematologic recovery (CRi) per European Leukemia Net (ELN) 2017 classification, determined by study investigators.CR was defined as bone marrow (BM) blasts \<5%; absence of circulating blasts and blasts with Auer rods;absence of extramedullary disease;absolute neutrophil count (ANC) ≥1.0 × 10\^9/L (1000/microliter (μL));platelet count ≥100 × 10\^9/L (100000/μL). CRMRD- if studied pretreatment was defined as CR with negativity for genetic marker by real-time quantitative polymerase chain reaction (RT-qPCR) or CR with negativity by multi-color flow cytometry (MFC).CRi was defined as all CR criteria except for residual neutropenia (\<1.0 × 10\^9/L \[1000/μL\]) or thrombocytopenia (\<100 × 10\^9/L \[100000/μL\]). |
| Overall Remission Rate (ORR) | Up to 3.2 months | ORR=percentage of participants who achieved CR+CRMRD- +CRi +morphologic leukemia-free state (MLFS) +partial remission (PR) per the ELN 2017 classification.CR was defined as BM blasts \<5%;absence of circulating blasts and blasts with Auer rods;absence of extramedullary disease;ANC ≥1.0 × 10\^9/L (1000/ (μL));platelet count ≥100 × 10\^9/L (100000/μL).CRMRD- if studied pretreatment = CR with negativity for genetic marker by RT-qPCR or CR with negativity by MFC.CRi was defined as all CR criteria except for residual neutropenia (\<1.0 × 10\^9/L \[1000/μL\]) or thrombocytopenia (\<100 × 10\^9/L \[100000/μL\]). MLFS=BM blasts \<5%;absence of blasts with Auer rods;absence of extramedullary disease;no hematologic recovery required.PR=hematologic criteria of CR decrease of BM blast percentage to 5% to 25%;and decrease of pretreatment BM blast percentage by at least 50%. |
| Relapse-free Survival (RFS) | Up to 3.2 months | For participants who experience CR, CRMRD-, or CRi, RFS was defined as the time between their first CR/CRMRD-/CRi to relapse or death due to any cause. CR was defined as BM blasts \<5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) ≥1.0 × 10\^9/L (1000/μL); platelet count ≥100 × 10\^9/L (100000/μL). CRMRD- if studied pretreatment was defined as CR with negativity for a genetic marker by RT-qPCR or CR with negativity by MFC. CR with incomplete hematologic recovery was defined as all CR criteria except for residual neutropenia (\<1.0 × 10\^9/L \[1000/μL\]) or thrombocytopenia (\<100 × 10\^9/L \[100000/μL\]). |
| Allogeneic Stem Cell Transplant (Allo-SCT) Rate | Up to 3.2 months | The allo-SCT rate was defined as the number of participants who received allo-SCT after being treated with KITE-222 divided by the total number of subjects included in the safety analysis set. |
| Event-free Survival (EFS) | Up to 12.3 months | EFS was defined as the time from the KITE-222 infusion date to earliest date of disease relapse,progressive disease (PD),refractory disease, or death due to any cause.Relapse: Hematologic : BM blasts ≥ 5%,reappearance of blasts, or development of extramedullary disease;Molecular:If studied before treatment, re-occurrence of MRD assessed by RT-qPCR or MFC, PD:Evidence for increase in BM blast percentage and/or increase of absolute blast counts in blood:\> 50% increase in marrow blasts over baseline(minimum 15% point increase required with \< 30% blasts at baseline or persistent marrow blast \> 70%over 3 months without ≥ 100% improvement in ANC to absolute level (\> 0.5 × 10\^9/L \[500/μL\], and/or platelet count to \> 50 × 10\^9/L \[50,000/μL\] nontransfused); \> 50% increase in peripheral blasts(white blood cells (WBC) x % blasts) to \> 25 × 10\^9/L (\>25,000/μL) (absence of differentiation syndrome);New extramedullary disease.Refractory disease:No CR, CRMRD-, or CRi by Week 6 disease assessment. |
| Percentage of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) | Up to 3.2 months | An AE was defined as any untoward medical occurrence in a clinical trial participant. The event does not necessarily have a relationship with the study treatment. The definition of an AE includes a worsening of a pre-existing medical condition. Worsening indicates that the pre-existing medical condition has increased in severity, frequency, and/or duration or has an association with a worse outcome. TEAEs were defined as any AEs with onset on or after the date of KITE-222 infusion. |
| All-cause Mortality Within 30 Days of KITE-222 Infusion | Up to 30 days | The mortality was calculated by number of deaths, regardless of cause, within 30 days from the KITE-222 infusion date. |
| All-cause Mortality Within 60 Days of KITE-222 Infusion | Up to 60 days | The mortality was calculated by number of deaths, regardless of cause, within 60 days from the KITE-222 infusion date. |
| Pharmacokinetics (PK) Parameter: Peak Level of KITE-222 CAR T Cells in Blood | Baseline (Day 0), post dose on Days 3, 7,10, Weeks 2, 3, 4, and 6 | Peak was defined as the maximum number of CAR T cells in blood measured after infusion. |
| PK Parameter: Area Under the Curve for the Blood Level of KITE-222 CAR T Cells From Day 0 to Day 28 (AUC0-28) | Baseline (Day 0), post dose on Days 3, 7, 10, Weeks 2, 3, and 4 | AUC0-28 was defined as the area under curve in a plot of number of CAR T cells against scheduled visit from Day 0 to Day 28. |
| Pharmacodynamics (PD) Parameter: Peak Serum Levels of Interferon-gamma (IFNg), Interleukin (IL)-12 P40, IL-10, and IL-15 | Baseline (Day 0), post dose on Days 1, 3, 5, 7, 9, 11, 13, Weeks 2, 3, 4 | Peak was defined as the maximum levels of Interferon-gamma (IFNg), Interleukin (IL)-12 P40, IL-10, and IL-15 in serum from baseline to Week 4. |
| PD Parameter: Peak Serum Levels of IL-2 R Alpha and Ferritin | Baseline (Day 0), post dose on Days 1, 3, 5, 7, 9, 11, 13, Weeks 2, 3, 4 | Peak was defined as the maximum levels of IL-2 R Alpha and Ferritin in serum from baseline to Week 4. |
| PD Parameter: AUC0-28 for the Serum Levels IFNg, IL-12 P40, IL-10, and IL-15 in Serum | Baseline (Day 0), post dose on Days 1, 3, 5, 7, 9, 11, 13, Weeks 2, 3, 4 | AUC0-28 was defined as the area under curve in a plot of IFNg, IL-12 P40, IL-10, and IL-15 scheduled visit from Day 0 to Day 28. |
| PD Parameter: AUC0-28 for the Serum Levels of IL-2 R Alpha and Ferritin | Baseline (Day 0), post dose on Days 1, 3, 5, 7, 9, 11, 13, Weeks 2, 3, 4 | AUC0-28 was defined as the area under curve in a plot of IL-2 R Alpha and Ferritin scheduled visit from Day 0 to Day 28. |
| Percentage of Participants Who Develop Anti-KITE-222 CAR Antibodies | Up to 3.2 months | — |
| Overall Survival (OS) | Up to 12.3 months | OS was defined as the time from KITE-222 infusion to the date of death from any cause. |
Countries
France, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in France and the United States.
Pre-assignment details
17 participants were screened. Dose expansion cohort was not initiated due to early termination of the study. There were no participants enrolled in the expansion cohort.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: KITE-222 (Low Dose) Participants with r/r AML received lymphodepleting chemotherapy (fludarabine and cyclophosphamide) followed by a single infusion of KITE-222 CAR transduced autologous T cells administered IV at a low dose on Day 0 based on participants body weight. | 3 |
| Cohort 2: KITE-222 (Higher Dose) Participants with r/r AML received lymphodepleting chemotherapy (fludarabine and cyclophosphamide) followed by a single infusion of KITE-222 CAR transduced autologous T cells administered IV at a higher dose on Day 0 based on participants body weight. | 3 |
| Cohort 3: KITE-222 (Highest Dose) Participants with r/r AML received lymphodepleting chemotherapy (fludarabine and cyclophosphamide) followed by a single infusion of KITE-222 CAR transduced autologous T cells administered IV at the highest dose on Day 0 based on participants body weight. | 6 |
| Total~(N=12) | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 4 | 3 | 6 |
| Overall Study | Did not meet eligibility criteria | 1 | 0 | 0 |
| Overall Study | Participant withdrawal of consent from further follow-up | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort 3: KITE-222 (Highest Dose) | Cohort 1: KITE-222 (Low Dose) | Total~(N=12) | Cohort 2: KITE-222 (Higher Dose) |
|---|---|---|---|---|
| Age, Continuous | 56 years STANDARD_DEVIATION 13.3 | 60 years STANDARD_DEVIATION 13.9 | 56 years STANDARD_DEVIATION 12 | 54 years STANDARD_DEVIATION 11.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 2 Participants | 10 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Black or African American | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Other or More Than One Race | 1 Participants | 1 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 4 Participants | 2 Participants | 8 Participants | 2 Participants |
| Region of Enrollment France | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Region of Enrollment United States | 4 Participants | 3 Participants | 10 Participants | 3 Participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 5 Participants | 1 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 7 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 5 | 3 / 3 | 7 / 7 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 6 / 6 |
| serious Total, serious adverse events | 3 / 3 | 2 / 3 | 4 / 6 |
Outcome results
Primary
Percentage of Participants Who Experienced Dose Limiting Toxicities (DLTs)
DLTs defined as KITE-222-related events with an onset within the first 28 days after the KITE-222 infusion:Grade(GR) 5 event,GR 4 cytokine release syndrome(CRS) or GR 3 CRS not improving to ≤ GR 2 by 72 hours,≥GR 3 cardiac and/or pulmonary event(Exceptions:related to CRS and improve to ≤GR 2 by 72 hours, managed by noninvasive care & resolves to baseline by Day28),GR 4 immune-effector cell-associated neurotoxicity syndrome(ICANS) or other GR 4 adverse events(AEs)associated to neurologic events,GR 3 ICANS(Exceptions: GR 3 ICANS based only on immune-effector cell-associated encephalopathy(ICE) score and/or depressed level of consciousness that improves to ≤GR 2 by 72 hours),≥GR 3 infusion or immediate hypersensitivity reaction,Ongoing GR 4 neutropenia or thrombocytopenia(not due to leukemia persistence)by Day 42 to who have not had conditioning regimen for allo-stem cell transplant,other KITE-222 related GR 3 non-hematologic AEs lasting \>7 days,KITE-222-related GR 4 non-hematologic AEs.
Time frame: Up to 28 days
Population: DLT-evaluable set consisted of participants treated in each dose-escalation cohort who:~* Received the target dose and were followed for at least 28 days after infusion of KITE-222; or~* Received a dose of KITE-222 that was lower than the target for that cohort and experienced a DLT during the 28-day post infusion period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: KITE-222 (Low Dose) | Percentage of Participants Who Experienced Dose Limiting Toxicities (DLTs) | 0 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Percentage of Participants Who Experienced Dose Limiting Toxicities (DLTs) | 0 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Percentage of Participants Who Experienced Dose Limiting Toxicities (DLTs) | 20 percentage of participants |
Secondary
All-cause Mortality Within 30 Days of KITE-222 Infusion
The mortality was calculated by number of deaths, regardless of cause, within 30 days from the KITE-222 infusion date.
Time frame: Up to 30 days
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: KITE-222 (Low Dose) | All-cause Mortality Within 30 Days of KITE-222 Infusion | 0 Participants |
| Cohort 2: KITE-222 (Higher Dose) | All-cause Mortality Within 30 Days of KITE-222 Infusion | 0 Participants |
| Cohort 3: KITE-222 (Highest Dose) | All-cause Mortality Within 30 Days of KITE-222 Infusion | 1 Participants |
Secondary
All-cause Mortality Within 60 Days of KITE-222 Infusion
The mortality was calculated by number of deaths, regardless of cause, within 60 days from the KITE-222 infusion date.
Time frame: Up to 60 days
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: KITE-222 (Low Dose) | All-cause Mortality Within 60 Days of KITE-222 Infusion | 1 Participants |
| Cohort 2: KITE-222 (Higher Dose) | All-cause Mortality Within 60 Days of KITE-222 Infusion | 0 Participants |
| Cohort 3: KITE-222 (Highest Dose) | All-cause Mortality Within 60 Days of KITE-222 Infusion | 3 Participants |
Secondary
Allogeneic Stem Cell Transplant (Allo-SCT) Rate
The allo-SCT rate was defined as the number of participants who received allo-SCT after being treated with KITE-222 divided by the total number of subjects included in the safety analysis set.
Time frame: Up to 3.2 months
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: KITE-222 (Low Dose) | Allogeneic Stem Cell Transplant (Allo-SCT) Rate | 0 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Allogeneic Stem Cell Transplant (Allo-SCT) Rate | 0 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Allogeneic Stem Cell Transplant (Allo-SCT) Rate | 0 percentage of participants |
Secondary
Composite Complete Remission (CCR) Rate
CCR rate=Percentage of participants who achieve complete remission (CR) + CR without measurable residual disease (CRMRD-) + CR with incomplete hematologic recovery (CRi) per European Leukemia Net (ELN) 2017 classification, determined by study investigators.CR was defined as bone marrow (BM) blasts \<5%; absence of circulating blasts and blasts with Auer rods;absence of extramedullary disease;absolute neutrophil count (ANC) ≥1.0 × 10\^9/L (1000/microliter (μL));platelet count ≥100 × 10\^9/L (100000/μL). CRMRD- if studied pretreatment was defined as CR with negativity for genetic marker by real-time quantitative polymerase chain reaction (RT-qPCR) or CR with negativity by multi-color flow cytometry (MFC).CRi was defined as all CR criteria except for residual neutropenia (\<1.0 × 10\^9/L \[1000/μL\]) or thrombocytopenia (\<100 × 10\^9/L \[100000/μL\]).
Time frame: Up to 3.2 months
Population: The participants in the modified intent-to-treat (mITT) analysis set were planned to be analyzed. mITT analysis set were to include all participants enrolled \& treated with at least 50% optimal dose of KITE-222 including all participants treated in both dose escalation \& dose expansion cohort. Study was discontinued at end of the dose escalation without starting the expansion cohort. Participants in Safety Analysis set were reported.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: KITE-222 (Low Dose) | Composite Complete Remission (CCR) Rate | 0 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Composite Complete Remission (CCR) Rate | 0 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Composite Complete Remission (CCR) Rate | 0 percentage of participants |
Secondary
Event-free Survival (EFS)
EFS was defined as the time from the KITE-222 infusion date to earliest date of disease relapse,progressive disease (PD),refractory disease, or death due to any cause.Relapse: Hematologic : BM blasts ≥ 5%,reappearance of blasts, or development of extramedullary disease;Molecular:If studied before treatment, re-occurrence of MRD assessed by RT-qPCR or MFC, PD:Evidence for increase in BM blast percentage and/or increase of absolute blast counts in blood:\> 50% increase in marrow blasts over baseline(minimum 15% point increase required with \< 30% blasts at baseline or persistent marrow blast \> 70%over 3 months without ≥ 100% improvement in ANC to absolute level (\> 0.5 × 10\^9/L \[500/μL\], and/or platelet count to \> 50 × 10\^9/L \[50,000/μL\] nontransfused); \> 50% increase in peripheral blasts(white blood cells (WBC) x % blasts) to \> 25 × 10\^9/L (\>25,000/μL) (absence of differentiation syndrome);New extramedullary disease.Refractory disease:No CR, CRMRD-, or CRi by Week 6 disease assessment.
Time frame: Up to 12.3 months
Population: The participants in the mITT analysis set were planned to be analyzed. mITT analysis set were to include all participants enrolled and treated with at least 50% of the optimal dose of KITE-222 including all participants treated in both the dose escalation cohort and the expansion cohort. The study was discontinued at the end of the dose escalation without starting the expansion cohort. Participants in the Safety Analysis Set were reported.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: KITE-222 (Low Dose) | Event-free Survival (EFS) | 26 days |
| Cohort 2: KITE-222 (Higher Dose) | Event-free Survival (EFS) | 23 days |
| Cohort 3: KITE-222 (Highest Dose) | Event-free Survival (EFS) | 21.5 days |
Secondary
Overall Remission Rate (ORR)
ORR=percentage of participants who achieved CR+CRMRD- +CRi +morphologic leukemia-free state (MLFS) +partial remission (PR) per the ELN 2017 classification.CR was defined as BM blasts \<5%;absence of circulating blasts and blasts with Auer rods;absence of extramedullary disease;ANC ≥1.0 × 10\^9/L (1000/ (μL));platelet count ≥100 × 10\^9/L (100000/μL).CRMRD- if studied pretreatment = CR with negativity for genetic marker by RT-qPCR or CR with negativity by MFC.CRi was defined as all CR criteria except for residual neutropenia (\<1.0 × 10\^9/L \[1000/μL\]) or thrombocytopenia (\<100 × 10\^9/L \[100000/μL\]). MLFS=BM blasts \<5%;absence of blasts with Auer rods;absence of extramedullary disease;no hematologic recovery required.PR=hematologic criteria of CR decrease of BM blast percentage to 5% to 25%;and decrease of pretreatment BM blast percentage by at least 50%.
Time frame: Up to 3.2 months
Population: The participants in mITT analysis set were planned to be analyzed. mITT analysis set were to include all participants enrolled \& treated with at least 50% optimal dose of KITE-222 including all participants treated in both dose escalation \& expansion cohort. Study was discontinued at end of the dose escalation without starting the expansion cohort. Participants in the Safety Analysis Set were reported.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: KITE-222 (Low Dose) | Overall Remission Rate (ORR) | 0 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Overall Remission Rate (ORR) | 0 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Overall Remission Rate (ORR) | 16.67 percentage of participants |
Secondary
Overall Survival (OS)
OS was defined as the time from KITE-222 infusion to the date of death from any cause.
Time frame: Up to 12.3 months
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: KITE-222 (Low Dose) | Overall Survival (OS) | 2.6 months |
| Cohort 2: KITE-222 (Higher Dose) | Overall Survival (OS) | 4.7 months |
| Cohort 3: KITE-222 (Highest Dose) | Overall Survival (OS) | 2.6 months |
Secondary
PD Parameter: AUC0-28 for the Serum Levels IFNg, IL-12 P40, IL-10, and IL-15 in Serum
AUC0-28 was defined as the area under curve in a plot of IFNg, IL-12 P40, IL-10, and IL-15 scheduled visit from Day 0 to Day 28.
Time frame: Baseline (Day 0), post dose on Days 1, 3, 5, 7, 9, 11, 13, Weeks 2, 3, 4
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: KITE-222 (Low Dose) | PD Parameter: AUC0-28 for the Serum Levels IFNg, IL-12 P40, IL-10, and IL-15 in Serum | IL-10 | 148.15 pg/mL*days |
| Cohort 1: KITE-222 (Low Dose) | PD Parameter: AUC0-28 for the Serum Levels IFNg, IL-12 P40, IL-10, and IL-15 in Serum | IFNg | 1051.60 pg/mL*days |
| Cohort 1: KITE-222 (Low Dose) | PD Parameter: AUC0-28 for the Serum Levels IFNg, IL-12 P40, IL-10, and IL-15 in Serum | IL-15 | 415.15 pg/mL*days |
| Cohort 1: KITE-222 (Low Dose) | PD Parameter: AUC0-28 for the Serum Levels IFNg, IL-12 P40, IL-10, and IL-15 in Serum | IL-12 P40 | 575.20 pg/mL*days |
| Cohort 2: KITE-222 (Higher Dose) | PD Parameter: AUC0-28 for the Serum Levels IFNg, IL-12 P40, IL-10, and IL-15 in Serum | IL-10 | 108.95 pg/mL*days |
| Cohort 2: KITE-222 (Higher Dose) | PD Parameter: AUC0-28 for the Serum Levels IFNg, IL-12 P40, IL-10, and IL-15 in Serum | IL-12 P40 | 1534.05 pg/mL*days |
| Cohort 2: KITE-222 (Higher Dose) | PD Parameter: AUC0-28 for the Serum Levels IFNg, IL-12 P40, IL-10, and IL-15 in Serum | IFNg | 451.50 pg/mL*days |
| Cohort 2: KITE-222 (Higher Dose) | PD Parameter: AUC0-28 for the Serum Levels IFNg, IL-12 P40, IL-10, and IL-15 in Serum | IL-15 | 668.60 pg/mL*days |
| Cohort 3: KITE-222 (Highest Dose) | PD Parameter: AUC0-28 for the Serum Levels IFNg, IL-12 P40, IL-10, and IL-15 in Serum | IL-12 P40 | 391.60 pg/mL*days |
| Cohort 3: KITE-222 (Highest Dose) | PD Parameter: AUC0-28 for the Serum Levels IFNg, IL-12 P40, IL-10, and IL-15 in Serum | IFNg | 7317.53 pg/mL*days |
| Cohort 3: KITE-222 (Highest Dose) | PD Parameter: AUC0-28 for the Serum Levels IFNg, IL-12 P40, IL-10, and IL-15 in Serum | IL-15 | 1021.05 pg/mL*days |
| Cohort 3: KITE-222 (Highest Dose) | PD Parameter: AUC0-28 for the Serum Levels IFNg, IL-12 P40, IL-10, and IL-15 in Serum | IL-10 | 809.58 pg/mL*days |
Secondary
PD Parameter: AUC0-28 for the Serum Levels of IL-2 R Alpha and Ferritin
AUC0-28 was defined as the area under curve in a plot of IL-2 R Alpha and Ferritin scheduled visit from Day 0 to Day 28.
Time frame: Baseline (Day 0), post dose on Days 1, 3, 5, 7, 9, 11, 13, Weeks 2, 3, 4
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: KITE-222 (Low Dose) | PD Parameter: AUC0-28 for the Serum Levels of IL-2 R Alpha and Ferritin | IL-2 R Alpha | 114.36 ng /mL*days |
| Cohort 1: KITE-222 (Low Dose) | PD Parameter: AUC0-28 for the Serum Levels of IL-2 R Alpha and Ferritin | Ferritin | 208000 ng /mL*days |
| Cohort 2: KITE-222 (Higher Dose) | PD Parameter: AUC0-28 for the Serum Levels of IL-2 R Alpha and Ferritin | IL-2 R Alpha | 56.61 ng /mL*days |
| Cohort 2: KITE-222 (Higher Dose) | PD Parameter: AUC0-28 for the Serum Levels of IL-2 R Alpha and Ferritin | Ferritin | 119000 ng /mL*days |
| Cohort 3: KITE-222 (Highest Dose) | PD Parameter: AUC0-28 for the Serum Levels of IL-2 R Alpha and Ferritin | IL-2 R Alpha | 302.03 ng /mL*days |
| Cohort 3: KITE-222 (Highest Dose) | PD Parameter: AUC0-28 for the Serum Levels of IL-2 R Alpha and Ferritin | Ferritin | 282000 ng /mL*days |
Secondary
PD Parameter: Peak Serum Levels of IL-2 R Alpha and Ferritin
Peak was defined as the maximum levels of IL-2 R Alpha and Ferritin in serum from baseline to Week 4.
Time frame: Baseline (Day 0), post dose on Days 1, 3, 5, 7, 9, 11, 13, Weeks 2, 3, 4
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: KITE-222 (Low Dose) | PD Parameter: Peak Serum Levels of IL-2 R Alpha and Ferritin | IL-2 R Alpha | 5.15 nanograms per milliliter (ng/mL) |
| Cohort 1: KITE-222 (Low Dose) | PD Parameter: Peak Serum Levels of IL-2 R Alpha and Ferritin | Ferritin | 16200 nanograms per milliliter (ng/mL) |
| Cohort 2: KITE-222 (Higher Dose) | PD Parameter: Peak Serum Levels of IL-2 R Alpha and Ferritin | IL-2 R Alpha | 2.90 nanograms per milliliter (ng/mL) |
| Cohort 2: KITE-222 (Higher Dose) | PD Parameter: Peak Serum Levels of IL-2 R Alpha and Ferritin | Ferritin | 11200 nanograms per milliliter (ng/mL) |
| Cohort 3: KITE-222 (Highest Dose) | PD Parameter: Peak Serum Levels of IL-2 R Alpha and Ferritin | IL-2 R Alpha | 21.32 nanograms per milliliter (ng/mL) |
| Cohort 3: KITE-222 (Highest Dose) | PD Parameter: Peak Serum Levels of IL-2 R Alpha and Ferritin | Ferritin | 27900 nanograms per milliliter (ng/mL) |
Secondary
Percentage of Participants Who Develop Anti-KITE-222 CAR Antibodies
Time frame: Up to 3.2 months
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: KITE-222 (Low Dose) | Percentage of Participants Who Develop Anti-KITE-222 CAR Antibodies | 0 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Percentage of Participants Who Develop Anti-KITE-222 CAR Antibodies | 0 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Percentage of Participants Who Develop Anti-KITE-222 CAR Antibodies | 0 percentage of participants |
Secondary
Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value
Grading categories are determined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Grade 1: mild, Grade 2: moderate, Grade 3: severe or medically significant, Grade 4: life-threatening; Grade 5: Death related to AE.
Time frame: Up to 3.2 months
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: KITE-222 (Low Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Hematology: Lymphocytes | 100 percentage of participants |
| Cohort 1: KITE-222 (Low Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Chemistry: Potassium | 33 percentage of participants |
| Cohort 1: KITE-222 (Low Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Chemistry: Albumin | 0 percentage of participants |
| Cohort 1: KITE-222 (Low Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Chemistry: Sodium | 0 percentage of participants |
| Cohort 1: KITE-222 (Low Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Chemistry: Magnesium | 0 percentage of participants |
| Cohort 1: KITE-222 (Low Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Hematology: Neutrophils | 0 percentage of participants |
| Cohort 1: KITE-222 (Low Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Hematology: Leukocytes | 33 percentage of participants |
| Cohort 1: KITE-222 (Low Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Chemistry: Phosphate | 0 percentage of participants |
| Cohort 1: KITE-222 (Low Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Chemistry: Glucose | 0 percentage of participants |
| Cohort 1: KITE-222 (Low Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Hematology: Hemoglobin | 67 percentage of participants |
| Cohort 1: KITE-222 (Low Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Chemistry: Calcium | 33 percentage of participants |
| Cohort 1: KITE-222 (Low Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Hematology: Platelets | 33 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Chemistry: Glucose | 0 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Chemistry: Albumin | 0 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Chemistry: Phosphate | 67 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Chemistry: Calcium | 0 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Chemistry: Potassium | 0 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Chemistry: Magnesium | 0 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Chemistry: Sodium | 0 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Hematology: Lymphocytes | 67 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Hematology: Hemoglobin | 33 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Hematology: Leukocytes | 67 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Hematology: Platelets | 0 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Hematology: Neutrophils | 33 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Hematology: Lymphocytes | 83 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Chemistry: Phosphate | 67 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Hematology: Neutrophils | 17 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Hematology: Hemoglobin | 50 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Chemistry: Albumin | 33 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Hematology: Platelets | 50 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Chemistry: Magnesium | 0 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Chemistry: Potassium | 50 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Hematology: Leukocytes | 67 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Chemistry: Sodium | 17 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Chemistry: Calcium | 33 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value | Chemistry: Glucose | 0 percentage of participants |
Secondary
Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value
Grading categories are determined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Grade 1: mild, Grade 2: moderate, Grade 3: severe or medically significant, Grade 4: life-threatening; Grade 5: Death related to AE.
Time frame: Up to 3.2 months
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: KITE-222 (Low Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Alkaline Phosphatase | 0 percentage of participants |
| Cohort 1: KITE-222 (Low Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Alanine Aminotransferase | 0 percentage of participants |
| Cohort 1: KITE-222 (Low Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Urate | 0 percentage of participants |
| Cohort 1: KITE-222 (Low Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Aspartate Aminotransferase | 0 percentage of participants |
| Cohort 1: KITE-222 (Low Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Bilirubin | 0 percentage of participants |
| Cohort 1: KITE-222 (Low Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Sodium | 0 percentage of participants |
| Cohort 1: KITE-222 (Low Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Calcium | 0 percentage of participants |
| Cohort 1: KITE-222 (Low Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Hematology: Lymphocytes | 0 percentage of participants |
| Cohort 1: KITE-222 (Low Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Potassium | 0 percentage of participants |
| Cohort 1: KITE-222 (Low Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Magnesium | 0 percentage of participants |
| Cohort 1: KITE-222 (Low Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Glucose | 33 percentage of participants |
| Cohort 1: KITE-222 (Low Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Creatinine | 0 percentage of participants |
| Cohort 1: KITE-222 (Low Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Direct Bilirubin | 0 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Creatinine | 0 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Magnesium | 0 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Sodium | 0 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Urate | 0 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Alanine Aminotransferase | 0 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Hematology: Lymphocytes | 0 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Alkaline Phosphatase | 0 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Direct Bilirubin | 33 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Aspartate Aminotransferase | 33 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Bilirubin | 0 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Calcium | 33 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Potassium | 0 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Glucose | 100 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Hematology: Lymphocytes | 17 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Bilirubin | 17 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Direct Bilirubin | 33 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Glucose | 17 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Alanine Aminotransferase | 17 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Alkaline Phosphatase | 0 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Aspartate Aminotransferase | 17 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Potassium | 0 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Creatinine | 33 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Magnesium | 17 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Sodium | 0 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Urate | 33 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value | Chemistry: Calcium | 33 percentage of participants |
Secondary
Percentage of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs)
An AE was defined as any untoward medical occurrence in a clinical trial participant. The event does not necessarily have a relationship with the study treatment. The definition of an AE includes a worsening of a pre-existing medical condition. Worsening indicates that the pre-existing medical condition has increased in severity, frequency, and/or duration or has an association with a worse outcome. TEAEs were defined as any AEs with onset on or after the date of KITE-222 infusion.
Time frame: Up to 3.2 months
Population: The Safety Analysis Set consisted of all participants treated with any dose of KITE-222.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: KITE-222 (Low Dose) | Percentage of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) | 100 percentage of participants |
| Cohort 2: KITE-222 (Higher Dose) | Percentage of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) | 100 percentage of participants |
| Cohort 3: KITE-222 (Highest Dose) | Percentage of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) | 100 percentage of participants |
Secondary
Pharmacodynamics (PD) Parameter: Peak Serum Levels of Interferon-gamma (IFNg), Interleukin (IL)-12 P40, IL-10, and IL-15
Peak was defined as the maximum levels of Interferon-gamma (IFNg), Interleukin (IL)-12 P40, IL-10, and IL-15 in serum from baseline to Week 4.
Time frame: Baseline (Day 0), post dose on Days 1, 3, 5, 7, 9, 11, 13, Weeks 2, 3, 4
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: KITE-222 (Low Dose) | Pharmacodynamics (PD) Parameter: Peak Serum Levels of Interferon-gamma (IFNg), Interleukin (IL)-12 P40, IL-10, and IL-15 | IFNg | 89.80 picograms per milliliter (pg/mL) |
| Cohort 1: KITE-222 (Low Dose) | Pharmacodynamics (PD) Parameter: Peak Serum Levels of Interferon-gamma (IFNg), Interleukin (IL)-12 P40, IL-10, and IL-15 | IL-12 P40 | 22.30 picograms per milliliter (pg/mL) |
| Cohort 1: KITE-222 (Low Dose) | Pharmacodynamics (PD) Parameter: Peak Serum Levels of Interferon-gamma (IFNg), Interleukin (IL)-12 P40, IL-10, and IL-15 | IL-10 | 9.60 picograms per milliliter (pg/mL) |
| Cohort 1: KITE-222 (Low Dose) | Pharmacodynamics (PD) Parameter: Peak Serum Levels of Interferon-gamma (IFNg), Interleukin (IL)-12 P40, IL-10, and IL-15 | IL-15 | 30.30 picograms per milliliter (pg/mL) |
| Cohort 2: KITE-222 (Higher Dose) | Pharmacodynamics (PD) Parameter: Peak Serum Levels of Interferon-gamma (IFNg), Interleukin (IL)-12 P40, IL-10, and IL-15 | IL-15 | 51.00 picograms per milliliter (pg/mL) |
| Cohort 2: KITE-222 (Higher Dose) | Pharmacodynamics (PD) Parameter: Peak Serum Levels of Interferon-gamma (IFNg), Interleukin (IL)-12 P40, IL-10, and IL-15 | IFNg | 150.10 picograms per milliliter (pg/mL) |
| Cohort 2: KITE-222 (Higher Dose) | Pharmacodynamics (PD) Parameter: Peak Serum Levels of Interferon-gamma (IFNg), Interleukin (IL)-12 P40, IL-10, and IL-15 | IL-10 | 16.50 picograms per milliliter (pg/mL) |
| Cohort 2: KITE-222 (Higher Dose) | Pharmacodynamics (PD) Parameter: Peak Serum Levels of Interferon-gamma (IFNg), Interleukin (IL)-12 P40, IL-10, and IL-15 | IL-12 P40 | 195.80 picograms per milliliter (pg/mL) |
| Cohort 3: KITE-222 (Highest Dose) | Pharmacodynamics (PD) Parameter: Peak Serum Levels of Interferon-gamma (IFNg), Interleukin (IL)-12 P40, IL-10, and IL-15 | IL-15 | 99.65 picograms per milliliter (pg/mL) |
| Cohort 3: KITE-222 (Highest Dose) | Pharmacodynamics (PD) Parameter: Peak Serum Levels of Interferon-gamma (IFNg), Interleukin (IL)-12 P40, IL-10, and IL-15 | IL-12 P40 | 27.60 picograms per milliliter (pg/mL) |
| Cohort 3: KITE-222 (Highest Dose) | Pharmacodynamics (PD) Parameter: Peak Serum Levels of Interferon-gamma (IFNg), Interleukin (IL)-12 P40, IL-10, and IL-15 | IL-10 | 145.45 picograms per milliliter (pg/mL) |
| Cohort 3: KITE-222 (Highest Dose) | Pharmacodynamics (PD) Parameter: Peak Serum Levels of Interferon-gamma (IFNg), Interleukin (IL)-12 P40, IL-10, and IL-15 | IFNg | 1876.00 picograms per milliliter (pg/mL) |
Secondary
Pharmacokinetics (PK) Parameter: Peak Level of KITE-222 CAR T Cells in Blood
Peak was defined as the maximum number of CAR T cells in blood measured after infusion.
Time frame: Baseline (Day 0), post dose on Days 3, 7,10, Weeks 2, 3, 4, and 6
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: KITE-222 (Low Dose) | Pharmacokinetics (PK) Parameter: Peak Level of KITE-222 CAR T Cells in Blood | 2.18 cells per microliter (cells/µL) |
| Cohort 2: KITE-222 (Higher Dose) | Pharmacokinetics (PK) Parameter: Peak Level of KITE-222 CAR T Cells in Blood | 0.08 cells per microliter (cells/µL) |
| Cohort 3: KITE-222 (Highest Dose) | Pharmacokinetics (PK) Parameter: Peak Level of KITE-222 CAR T Cells in Blood | 3.88 cells per microliter (cells/µL) |
Secondary
PK Parameter: Area Under the Curve for the Blood Level of KITE-222 CAR T Cells From Day 0 to Day 28 (AUC0-28)
AUC0-28 was defined as the area under curve in a plot of number of CAR T cells against scheduled visit from Day 0 to Day 28.
Time frame: Baseline (Day 0), post dose on Days 3, 7, 10, Weeks 2, 3, and 4
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: KITE-222 (Low Dose) | PK Parameter: Area Under the Curve for the Blood Level of KITE-222 CAR T Cells From Day 0 to Day 28 (AUC0-28) | 25.09 cells/µL*days |
| Cohort 2: KITE-222 (Higher Dose) | PK Parameter: Area Under the Curve for the Blood Level of KITE-222 CAR T Cells From Day 0 to Day 28 (AUC0-28) | 0.47 cells/µL*days |
| Cohort 3: KITE-222 (Highest Dose) | PK Parameter: Area Under the Curve for the Blood Level of KITE-222 CAR T Cells From Day 0 to Day 28 (AUC0-28) | 26.66 cells/µL*days |
Secondary
Relapse-free Survival (RFS)
For participants who experience CR, CRMRD-, or CRi, RFS was defined as the time between their first CR/CRMRD-/CRi to relapse or death due to any cause. CR was defined as BM blasts \<5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) ≥1.0 × 10\^9/L (1000/μL); platelet count ≥100 × 10\^9/L (100000/μL). CRMRD- if studied pretreatment was defined as CR with negativity for a genetic marker by RT-qPCR or CR with negativity by MFC. CR with incomplete hematologic recovery was defined as all CR criteria except for residual neutropenia (\<1.0 × 10\^9/L \[1000/μL\]) or thrombocytopenia (\<100 × 10\^9/L \[100000/μL\]).
Time frame: Up to 3.2 months
Population: The participants in the mITT analysis set were planned to be analyzed. mITT analysis set were to include all participants enrolled and treated with at least 50% of the optimal dose of KITE-222 including all participants treated in both the dose escalation cohort and the expansion cohort. The study was discontinued at the end of the dose escalation without starting the expansion cohort. Since no participants experienced CR, CRMRD-, or CRi, RFS could not be evaluated.
Secondary
Time to Neutrophil Recovery
Time to neutrophil recovery after KITE-222 infusion & before the start of the conditioning therapy for allo-SCT was calculated as the time from the date of KITE-222 infusion to the first day when neutrophils are 0.5 × 10\^9/liter (L), and as the time from the date of KITE-222 infusion to the first day when neutrophils are 1.0 × 10\^9/L. Per European Leukemia Net (ELN) 2017 classification, determined by study investigators, CR was defined as bone marrow (BM) blasts \<5%; absence of circulating blasts and blasts with Auer rods;absence of extramedullary disease;absolute neutrophil count (ANC) ≥1.0 × 10\^9/L (1000/microliter (μL));platelet count ≥100 × 10\^9/L (100000/μL). CRi was defined as all CR criteria except for residual neutropenia (\<1.0 × 10\^9/L \[1000/μL\]) or thrombocytopenia (\<100 × 10\^9/L \[100000/μL\]).
Time frame: Up to 3.2 months
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: KITE-222 (Low Dose) | Time to Neutrophil Recovery | NA months |
| Cohort 2: KITE-222 (Higher Dose) | Time to Neutrophil Recovery | NA months |
| Cohort 3: KITE-222 (Highest Dose) | Time to Neutrophil Recovery | NA months |
Secondary
Time to Platelet Recovery
Time to platelet recovery after KITE-222 infusion and before the start of the conditioning therapy for subsequent allo-SCT was calculated as the time from the date of KITE-222 infusion to the first day when platelets are 50 × 10\^9/L, and the time from the date of KITE-222 infusion to the first day platelets are 100 × 10\^9/L. Per European Leukemia Net (ELN) 2017 classification, determined by study investigators, CR was defined as bone marrow (BM) blasts \<5%; absence of circulating blasts and blasts with Auer rods;absence of extramedullary disease;absolute neutrophil count (ANC) ≥1.0 × 10\^9/L (1000/microliter (μL));platelet count ≥100 × 10\^9/L (100000/μL). CRi was defined as all CR criteria except for residual neutropenia (\<1.0 × 10\^9/L \[1000/μL\]) or thrombocytopenia (\<100 × 10\^9/L \[100000/μL\]).
Time frame: Up to 3.2 months
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: KITE-222 (Low Dose) | Time to Platelet Recovery | NA months |
| Cohort 2: KITE-222 (Higher Dose) | Time to Platelet Recovery | NA months |
| Cohort 3: KITE-222 (Highest Dose) | Time to Platelet Recovery | NA months |