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 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).
Primary Objective: 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 subjects with r/r AML. Secondary Objectives: The secondary objectives of this study are as follows: -to evaluate the efficacy of KITE-222 in treating subjects with r/r AML -to evaluate the pharmacokinetic and pharmacodynamic profiles of KITE-222 in subjects with r/r AML Exploratory Objectives: The exploratory objectives of this study are as follows: -to explore the percentage CLL-1 expression on AML blasts from subjects at enrollment, and to determine if the expression correlates with the response -to explore the phenotypic and functional characteristics of KITE-222
Cell Therapy; Chemotherapy (NOS); Therapy (NOS)
KITE-222 (); cyclophosphamide (); cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)
- 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, as defined in protocol.
- Adequate renal, hepatic, pulmonary and cardiac function as defined in protocol.
- 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
- Other criteria may apply
- 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 cerebrovascular ischemia, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome, or any autoimmune disease with CNS involvement. History of seizures is acceptable if there are no episodes in the last 5 years. History of bleeding in the CNS is acceptable if related to thrombocytopenia of the AML, more than 12 months have elapsed, and there is complete resolution of symptoms and cerebral imaging.
- Presence or suspicion of a fungal, bacterial, viral, or other infection that is uncontrolled or requiring antimicrobials for management
- Live vaccine received within 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
- Other criteria may apply
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