Clinical Trials /

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

NCT04789408

Description:

The primary objective of this study is to evaluate the feasibility, safety, maximum tolerated dose (MTD), and optimal dose of KITE-222 in the treatment of participants with relapsed/refractory (r/r) acute myeloid leukemia (AML).

Related Conditions:
  • Acute Myeloid Leukemia
  • Secondary Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study Evaluating the Safety of KITE-222 in Participants With Relapsed/Refractory Acute Myeloid Leukemia
  • 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

Clinical Trial IDs

  • ORG STUDY ID: KT-US-486-0201
  • SECONDARY ID: 2020-000962-40
  • NCT ID: NCT04789408

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
CyclophosphamideKITE-222
FludarabineKITE-222
KITE-222KITE-222

Purpose

The primary objective of this study is to evaluate the feasibility, safety, maximum tolerated dose (MTD), and optimal dose of KITE-222 in the treatment of participants with relapsed/refractory (r/r) acute myeloid leukemia (AML).

Trial Arms

NameTypeDescriptionInterventions
KITE-222ExperimentalDose Escalation: Participants will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single target starting dose of KITE-222 chimeric antigen receptor (CAR) transduced autologous T cells. Based on dose limiting toxicities (DLTs) observed in the first cohort, additional participants will be enrolled and administered escalating dose of KITE-222 to determine the maximum tolerated dose (MTD) of KITE-222. Dose Expansion: Participants will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single dose (at the MTD determined) of KITE-222.
  • Cyclophosphamide
  • Fludarabine
  • KITE-222

Eligibility 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 allo-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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)
Time Frame:First infusion date of KITE-222 up to 28 days
Safety Issue:
Description:DLTs are defined as KITE-222-related events with an onset within the first 28 days after the KITE-222 infusion

Secondary Outcome Measures

Measure:Percentage of Participants Experiencing Adverse Events
Time Frame:Up to 15 years
Safety Issue:
Description:
Measure:Percentage of Participants Experiencing Clinically Significant Changes in Laboratory Parameters
Time Frame:Up to 15 years
Safety Issue:
Description:
Measure:Time to Neutrophil Recovery
Time Frame:First infusion date of KITE-222 up to 24 months
Safety Issue:
Description:
Measure:Time to Platelet Recovery
Time Frame:First infusion date of KITE-222 up to 24 months
Safety Issue:
Description:
Measure:Composite Complete Remission (CCR) Rate
Time Frame:Up to 24 months
Safety Issue:
Description:CCR rate is defined as the proportion of participants who achieve a complete remission (CR) plus the proportion of participants who achieve a CR without measurable residual disease (CRMRD-) plus the proportion of participants who achieve a CR with incomplete hematologic recovery (CRi) per the European Leukemia Net (ELN) 2017 classification, as determined by the study investigators.
Measure:Overall Remission Rate (ORR)
Time Frame:Up to 24 months
Safety Issue:
Description:ORR is defined as CR + CRMRD- + CRi + morphologic leukemia-free state (MLFS) + partial remission (PR) per the ELN 2017 classification, as determined by the study investigators.
Measure:Relapse-free Survival (RFS)
Time Frame:Up to 24 months
Safety Issue:
Description:For participants who experience CR, CRMRD-, or CRi, RFS is defined as the time between their first CR/CRMRD-/CRi to relapse or death due to any cause.
Measure:Allogeneic Stem Cell Transplant (allo-SCT) Rate
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Event-free Survival (EFS)
Time Frame:First infusion date of KITE-222 up to 24 months
Safety Issue:
Description:EFS is defined as the time from the KITE-222 infusion date to the earliest date of disease relapse, progressive disease, refractory disease, or death due to any cause.
Measure:Overall Survival (OS)
Time Frame:First infusion date of KITE-222 up to 15 years
Safety Issue:
Description:OS is defined as the time from KITE-222 infusion to the date of death from any cause.
Measure:30 Day All-cause Mortality Rate
Time Frame:First infusion date of KITE-222 up to 30 days
Safety Issue:
Description:The mortality rate is calculated by number of deaths, regardless of cause, within 30 days from the KITE-222 infusion date divided by the total number of participants included in the safety analysis set. The safety analysis set consists of all participants treated with any dose of KITE-222.
Measure:60 Day All-cause Mortality Rate
Time Frame:First infusion date of KITE-222 up to 60 days
Safety Issue:
Description:The mortality rate is calculated by number of deaths, regardless of cause, within 60 days from the KITE-222 infusion date divided by the total number of participants included in the safety analysis set. The safety analysis set consists of all participants treated with any dose of KITE-222.
Measure:Pharmacokinetics (PK): Peak Plasma Concentration of KITE-222 CAR T Cells in Participants With Relapsed/Refractory (r/r) Acute Myeloid Leukemia (AML) Treated with KITE-222
Time Frame:Enrollment (before leukapheresis) and D0 (predose), D3,7,10,14 &21, W4, PTFU (W6, M2,3,6,9,12,15,18 &24 and at relapse for participants without allo-SCT or within 1 W before CC, D-1 of allo-SCT, M1,3,6,12 &24 and at relapse for participants with allo-SCT
Safety Issue:
Description:PK will be assessed at enrollment (before start of leukapheresis) and Day 0 (predose) and on Days 3, 7, 10, 14 & 21, Week 4, post-treatment follow-up (Week 6, Months 2, 3, 6, 9, 12, 15, 18, & 24 and at relapse for participants without allo-SCT or within 1 week before conditioning chemotherapy and Day -1 of allo-SCT, Months 1, 3, 6,12 & 24 and at relapse for participants with allo-SCT). CC=conditioning chemotherapy D=Day(s) M=Month PTFU= post-treatment follow-up W=Week
Measure:PK Parameter: AUC of KITE-222 CAR T Cells in Participants With r/r AML Treated with KITE-222
Time Frame:Enrollment (before leukapheresis) and D0 (predose), D3,7,10,14 &21, W4, PTFU (W6, M2,3,6,9,12,15,18 &24 and at relapse for participants without allo-SCT or within 1 W before CC, D-1 of allo-SCT, M1,3,6,12 &24 and at relapse for participants with allo-SCT
Safety Issue:
Description:AUC is defined as the area under the concentration versus time curve. PK will be assessed at enrollment (before start of leukapheresis) and Day 0 (predose) and on Days 3, 7, 10, 14 & 21, Week 4, post-treatment follow-up (Week 6, Months 2, 3, 6, 9, 12, 15, 18, & 24 and at relapse for participants without allo-SCT or within 1 week before conditioning chemotherapy and Day -1 of allo-SCT, Months 1, 3, 6,12 & 24 and at relapse for participants with allo-SCT). CC=conditioning chemotherapy D=Day(s) M=Month PTFU= post-treatment follow-up W=Week
Measure:Pharmacodynamics (PD): Peak Plasma of Key Analytes (Pro-inflammatory and Immune-modulating Cytokines, Chemokines, and Effector Molecules) in Participants With r/r AML Treated with KITE-222
Time Frame:Enrollment (before leukapheresis) and Days -5 & 0 (predose) and Days 1-13 every other day,14,21, Week 4, post-treatment follow-up (Month 2 and at relapse for participants without allo-SCT or at relapse for participants with allo-SCT)
Safety Issue:
Description:
Measure:PD Parameter: AUC of Key Analytes (Pro-inflammatory and Immune-modulating Cytokines, Chemokines, and Effector Molecules) in Participants With r/r AML Treated with KITE-222
Time Frame:Enrollment (before leukapheresis) and Days -5 & 0 (predose) and Days 1-13 every other day,14,21, Week 4, post-treatment follow-up (Month 2 and at relapse for participants without allo-SCT or at relapse for participants with allo-SCT)
Safety Issue:
Description:AUC is defined as the area under the concentration versus time curve.
Measure:Percentage of Participants who Develop Anti-KITE-222 CAR Antibodies
Time Frame:Enrollment (before leukapheresis),Week 4, post-treatment follow-up (Month 3 and at relapse for participants without allo-SCT or within 1 week before conditioning chemotherapy and at relapse for participants with allo-SCT)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Gilead Sciences

Last Updated

June 16, 2021