Study of KITE-222 in Participants With Relapsed/Refractory Acute Myeloid Leukemia

A Phase 1 Open-label, Multicenter Study Evaluating the Safety of KITE-222, an Autologous Anti-CLL-1 CAR T-cell Therapy, in Subjects With Relapsed/Refractory Acute Myeloid Leukemia

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).

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: KITE-222

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Marseille, France, 13009
    • Institut Paoli-Calmettes
  • Toulouse, France, 3110
    • CHU de Toulouse Institut Universitaire du Cancer Toulouse Oncopole
• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford Cancer Center
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center/James Cancer Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: KITE-222 (Low Dose); Participants with relapsed or refractory (r/r) acute myeloid leukemia (AML) will receive lymphodepleting chemotherapy (fludarabine and cyclophosphamide) followed by a single infusion of KITE-222 chimeric antigen receptor (CAR) transduced autologous T cells administered intravenously (IV) at a low dose on Day 0 based on participants body weight.	Drug: Cyclophosphamide; Administered intravenously; Drug: Fludarabine; Administered intravenously; Biological: KITE-222; A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously
Experimental: Cohort 2: KITE-222 (Higher Dose); Participants with r/r AML will receive 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.	Drug: Cyclophosphamide; Administered intravenously; Drug: Fludarabine; Administered intravenously; Biological: KITE-222; A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously
Experimental: Cohort 3: KITE-222 (Highest Dose); Participants with r/r AML will receive 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.	Drug: Cyclophosphamide; Administered intravenously; Drug: Fludarabine; Administered intravenously; Biological: KITE-222; A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously
Experimental: Dose Expansion; Participants will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single dose [at the maximum tolerated dose (MTD) determined] of KITE-222.	Drug: Cyclophosphamide; Administered intravenously; Drug: Fludarabine; Administered intravenously; Biological: KITE-222; A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 3.2 months
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.	Up to 3.2 months
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.	Up to 3.2 months
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]).	Up to 3.2 months
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]).	Up to 3.2 months
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]).	Up to 3.2 months
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%.	Up to 3.2 months
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]).	Up to 3.2 months
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.	Up to 3.2 months
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.	Up to 12.3 months
Overall Survival (OS)	OS was defined as the time from KITE-222 infusion to the date of death from any cause.	Up to 12.3 months
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.	Up to 30 days
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.	Up to 60 days
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.	Baseline (Day 0), post dose on Days 3, 7,10, Weeks 2, 3, 4, and 6
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.	Baseline (Day 0), post dose on Days 3, 7, 10, Weeks 2, 3, and 4
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.	Baseline (Day 0), post dose on Days 1, 3, 5, 7, 9, 11, 13, Weeks 2, 3, 4
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.	Baseline (Day 0), post dose on Days 1, 3, 5, 7, 9, 11, 13, Weeks 2, 3, 4
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.	Baseline (Day 0), post dose on Days 1, 3, 5, 7, 9, 11, 13, Weeks 2, 3, 4
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.	Baseline (Day 0), post dose on Days 1, 3, 5, 7, 9, 11, 13, Weeks 2, 3, 4
Percentage of Participants Who Develop Anti-KITE-222 CAR Antibodies		Up to 3.2 months

Collaborators and Investigators

• Sponsor: Kite, A Gilead Company
• Investigators: Study Director: Kite Study Director, Kite, A Gilead Company

Publications and helpful links

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2021
• Primary Completion (Actual): May 18, 2024
• Study Completion (Actual): May 18, 2024

Study Registration Dates

• First Submitted: March 5, 2021
• First Submitted That Met QC Criteria: March 5, 2021
• First Posted (Actual): March 9, 2021

Study Record Updates

• Last Update Posted (Actual): July 11, 2025
• Last Update Submitted That Met QC Criteria: June 24, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine
• Other Study ID Numbers: KT-US-486-0201; 2020-000962-40 (EudraCT Number); 2023-507748-35 (Other Identifier: European Medicines Agency)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No