Relapsed/Refractory Acute Myeloid Leukemia
Conditions
Keywords
Relapsed/refractory acute myeloid leukemia, Acute myeloid leukemia, Oncology/hematology, CAR T cell therapy
Brief summary
Evaluate the safety and tolerability of AMG 553 in adult and adolescent subjects with FLT3-positive R/R AML. Determine the maximum tolerated cell dose (MTCD) or recommended phase 2 cell dose (RP2CD) of AMG 553.
Interventions
DRUGAMG 553
AMG 553 is a chimeric antigen T-cell receptor (CAR-T) therapy
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject has provided informed consent/assent prior to initiation of any study-specific activities/procedures. * Age greater than or equal to 12 years old at the time of signing the informed consent * Relapsed/Refractory Acute Myeloid Leukemia (AML) as defined by the World Health Organization (WHO) Classification as persisting or recurring following 1 or more treatment courses (exceptions noted in
Exclusion criteria
). Subjects must be intolerant to or ineligible for available therapies (eg, patients with FLT3 ITD/TKD mutations must have failed FLT3 inhibitors like midostaurin). * FLT3 positivity: FLT3 expression on myeloblasts must be confirmed by local lab flow cytometry using an antibody targeting CD135 (FLT3) * Myeloblasts greater than 5% in bone marrow and/or peripheral blood, as confirmed by immunophenotype by flow cytometry. * Subject must have a donor or stem cell source identified for allogeneic transplantation, either related (7/8 or 8/8 allele matched or haploidentical), unrelated (7/8 or 8/8 allele matched donor), or cord blood stem cell source (at least 4/6 matched). * Karnofsky performance score greater than or equal to 50 (for subjects aged greater than or equal to 16 years) or Lansky (for subjects aged less than 16 years) performance score greater than or equal to 50. * Adequate organ function, defined as follows: Coagulation function: prothrombin timeprothrombin time/international normalization ratio (PT/INR) and partial thromboplastin time (PTT) less than or equal to 1.5 x Institutional Upper Limit of Normal Renal function as follows: Estimated Glomerular filtration rate by institutional formula greater than 60 mL/min/1.73 m2 or serum creatinine less than 2 times upper limit of normal (ULN) for the subject's age. Hepatic function: aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase less than 3 X upper limit of normal ULN. Total bilirubin less than 1.5 X upper limit of normal ULN. Cardiac function: Cardiac ejection fraction greater than or equal to 50%, no evidence of pericardial effusion as determined by an echocardiogram or Multigated Acquisition (MUGA) scan, and no clinically significant ECG findings.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose limiting toxicities (DLTs) | 3 Months |
| Treatment-emergent adverse events | 3 months |
| Treatment-related adverse events | 3 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Morphologic leukemia-free state (MLFS) | 3 months | Evidence of anti-leukemic activity of AMG 553 |
| Duration of response (DOR) | 3 months | Evidence of anti-leukemic activity of AMG 553 |
| Progression free survival (PFS) | 3 months | Evidence of anti-leukemic activiy of AMG 553 |
| Complete response (CR) | 3 months | Evidence of anti-leukemic activity of AMG 553 |
| Proportion of subjects with minimal-residual disease (MRD) negative response | 3 Months | Evaluated proportion of subjects with minimal residual disease (MRD) negative response measured by flow cytometry in subjects achieving morphologic response defined by complete response (CR), complete response with partial recovery of peripheral blood counts (CRh), complete response with incomplete recovery of peripheral blood counts (CRi) measured by modified International Working Group (IWG) criteria. |
| The area under the concentration time-curve (AUC) of AMG 553 | 3 Months | Evaluate the cellular kinetics of AMG 553 post infusion |
| Peak levels of AMG 553 (maximum concentration or Cmax) | 3 months | Evaluate the cellular kinetics of AMG 553 post infusion |
| Overall Survival (OS) | 3 months | Evidence of anti-leukemic activity of AMG 553 |
| Complete response with partial recovery of peripheral blood counts (CRh) | 3 months | Evidence of anti-leukemic activity of AMG 553 |
| Complete response with incomplete recovery of peripheral blood counts (CRi) | 3 months | Evidence of anti-leukemic activity of AMG 553 |
Countries
United States
Outcome results
None listed