Clinical trial NCT04789408: Study 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2021-03-09
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)
timeFrame: First infusion date of KITE-222 up to 28 days
Secondary outcomes:
measure: Percentage of Participants Experiencing Adverse Events
timeFrame: Up to 15 years
measure: Percentage of Participants Experiencing Clinically Significant Changes in Laboratory Parameters
timeFrame: Up to 15 years
measure: Time to Neutrophil Recovery
timeFrame: First infusion date of KITE-222 up to 24 months
measure: Time to Platelet Recovery
timeFrame: First infusion date of KITE-222 up to 24 months
measure: Composite Complete Remission (CCR) Rate
timeFrame: Up to 24 months
measure: Overall Remission Rate (ORR)
timeFrame: Up to 24 months
measure: Relapse-free Survival (RFS)
timeFrame: Up to 24 months
measure: Allogeneic Stem Cell Transplant (allo-SCT) Rate
timeFrame: Up to 24 months
measure: Event-free Survival (EFS)
timeFrame: First infusion date of KITE-222 up to 24 months
measure: Overall Survival (OS)
timeFrame: First infusion date of KITE-222 up to 15 years
measure: 30 Day All-cause Mortality Rate
timeFrame: First infusion date of KITE-222 up to 30 days
measure: 60 Day All-cause Mortality Rate
timeFrame: First infusion date of KITE-222 up to 60 days
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
timeFrame: 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
measure: PK Parameter: AUC of KITE-222 CAR T Cells in Participants With r/r AML Treated with KITE-222
timeFrame: 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
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
timeFrame: 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)
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
timeFrame: 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)
measure: Percentage of Participants who Develop Anti-KITE-222 CAR Antibodies
timeFrame: 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)
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center/James Cancer Hospital
state: Ohio
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Toulouse
country: France
facility: CHU de Toulouse Institut Universitaire du Cancer Toulouse Oncopole
Study officials:
affiliation: Kite, A Gilead Company
name: Kite Study Director
role: STUDY_DIRECTOR
References: