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Acute Myeloid LeukemiaPhase 1NCT04789408

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

A Phase 1 study testing Cyclophosphamide, Fludarabine and KITE-222 in people with Acute Myeloid Leukemia, run by Kite, A Gilead Company at 9 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Cyclophosphamide, Fludarabine and KITE-222
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
9 sitesin 2 countries
Study dates
19 Jul 2021to 18 May 2024
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

9 sites in 2 countries.

9 sites in 2 countries

United States7 sites
  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • The Ohio State University Wexner Medical Center/James Cancer Hospital

    Columbus, Ohio, 43210

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Fred Hutchinson Cancer Center

    Seattle, Washington, 98109

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Stanford Cancer Center

    Stanford, California, 94305

  • Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

France2 sites
  • Institut Paoli-Calmettes

    Marseille, 13009

  • CHU de Toulouse Institut Universitaire du Cancer Toulouse Oncopole

    Toulouse, 3110

Other trials in France

About this study

Official title: 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).

Being tested
Cyclophosphamide, Fludarabine, KITE-222
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Administered intravenously

  • FludarabineDrug

    Administered intravenously

  • KITE-222Biological

    A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously

Study groups in NCT04789408
Study groupRoleWhat they receive
Cohort 1: KITE-222 (Low Dose)ExperimentalParticipants 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.
Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: KITE-222
Cohort 2: KITE-222 (Higher Dose)ExperimentalParticipants 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.
Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: KITE-222
Cohort 3: KITE-222 (Highest Dose)ExperimentalParticipants 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.
Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: KITE-222
Dose ExpansionExperimentalParticipants will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single dose [at the maximum tolerated dose (MTD) determined] of KITE-222.
Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: KITE-222

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 28 days

Secondary outcomes (20)
  1. 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.

    Measured: Up to 3.2 months

  2. 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.

    Measured: Up to 3.2 months

  3. 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.

    Measured: Up to 3.2 months

  4. 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]).

    Measured: Up to 3.2 months

  5. 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]).

    Measured: Up to 3.2 months

  6. 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]).

    Measured: Up to 3.2 months

  7. 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%.

    Measured: Up to 3.2 months

  8. 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]).

    Measured: Up to 3.2 months

  9. 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.

    Measured: Up to 3.2 months

  10. 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.

    Measured: Up to 12.3 months

  11. Overall Survival (OS)

    OS was defined as the time from KITE-222 infusion to the date of death from any cause.

    Measured: Up to 12.3 months

  12. 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.

    Measured: Up to 30 days

  13. 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.

    Measured: Up to 60 days

  14. 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.

    Measured: Baseline (Day 0), post dose on Days 3, 7,10, Weeks 2, 3, 4, and 6

  15. 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.

    Measured: Baseline (Day 0), post dose on Days 3, 7, 10, Weeks 2, 3, and 4

  16. 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.

    Measured: Baseline (Day 0), post dose on Days 1, 3, 5, 7, 9, 11, 13, Weeks 2, 3, 4

  17. 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.

    Measured: Baseline (Day 0), post dose on Days 1, 3, 5, 7, 9, 11, 13, Weeks 2, 3, 4

  18. 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.

    Measured: Baseline (Day 0), post dose on Days 1, 3, 5, 7, 9, 11, 13, Weeks 2, 3, 4

  19. 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.

    Measured: Baseline (Day 0), post dose on Days 1, 3, 5, 7, 9, 11, 13, Weeks 2, 3, 4

  20. Percentage of Participants Who Develop Anti-KITE-222 CAR Antibodies

    Measured: Up to 3.2 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Mar 2021
  2. Study start19 Jul 2021
  3. Primary completion18 May 2024
  4. Study completion18 May 2024

Why it stopped: Study was terminated due to futility

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04789408
Sponsor's protocol ID
KT-US-486-0201
Other IDs
2020-000962-40, 2023-507748-35, 2023
Status last verified
Jun 2025
First submitted
5 Mar 2021
Last updated
11 Jul 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cyclophosphamide, Fludarabine and KITE-222 in people with Acute Myeloid Leukemia, run by Kite, A Gilead Company at 9 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 11 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Who Experienced Dose Limiting Toxicities (DLTs) (time frame: Up to 28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2025.

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