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

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• Leukemia, Myeloid, Acute 2,971

Leukemia, Myeloid, Acute

2,971 studies on the registry are indexed under Leukemia, Myeloid, Acute; 745 are open to participants now.

This study's enrollment of 15 is below the median of 41 across 2,509 interventional studies indexed under Leukemia, Myeloid, Acute.

Lead sponsor

Kite, A Gilead Company is the lead sponsor of 36 studies on the registry; 7 are open to participants now.

Of its 18 completed or terminated interventional studies of FDA-regulated products, 14 (78%) have results posted.

Eligibility criteria

Study arms

• 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 · Drug: Fludarabine · Biological: KITE-222

• 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 · Drug: Fludarabine · Biological: KITE-222

• 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 · Drug: Fludarabine · Biological: KITE-222

• 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 · Drug: Fludarabine · Biological: KITE-222

Interventions

• DrugCyclophosphamide

  Administered intravenously

• DrugFludarabine

  Administered intravenously

• BiologicalKITE-222

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

Primary outcomes

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.

   Time frame: Up to 28 days

Secondary outcomes

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.

   Time frame: 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.

   Time frame: 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.

   Time frame: 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 \[100000/μL\]).

   Time frame: 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 \[100000/μL\]).

   Time frame: 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 \[100000/μL\]).

   Time frame: 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%.

   Time frame: 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 \[100000/μL\]).

   Time frame: 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.

   Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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

    Time frame: Up to 3.2 months

Baseline characteristics

Related links

• Gilead Clinical Trials Website ↗

Study documents

• Study protocol · Jan 17, 2023
• Statistical analysis plan · Jun 28, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No