Study Evaluating the Safety, Tolerability, and Efficacy of FLT3 CAR-T AMG 553 in FLT3-positive Relapsed/Refractory AML

NCT03904069 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: 20180091
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

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.

Conditions

Relapsed/Refractory Acute Myeloid Leukemia

Keywords

Relapsed/refractory acute myeloid leukemia; Acute myeloid leukemia; Oncology/hematology; CAR T cell therapy

Outcome Measures

Primary Outcomes (3)

• Dose limiting toxicities (DLTs)

  3 Months

• Treatment-emergent adverse events

  3 months

• Treatment-related adverse events

  3 months

Secondary Outcomes (10)

• Complete response (CR)

  3 months

• Complete response with partial recovery of peripheral blood counts (CRh)

  3 months

• Complete response with incomplete recovery of peripheral blood counts (CRi)

  3 months

• Morphologic leukemia-free state (MLFS)

  3 months

• Duration of response (DOR)

  3 months

Study Arms (1)

Comparison of different cell doses of AMG 553

EXPERIMENTAL

Subjects will receive IV infusion of AMG 553

Drug: AMG 553

Interventions

AMG 553 DRUG

AMG 553 is a chimeric antigen T-cell receptor (CAR-T) therapy

Comparison of different cell doses of AMG 553

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• Subjects with acute promyelocytic leukemia (APML).
• Active extramedullary AML in the central nervous system (CNS).
• Subjects with a prior or concurrent malignancy whose natural history or treatment is not anticipated to interfere with the safety or efficacy assessment of the investigational regimen may be included only after discussion with the Amgen Medical Monitor.
• History of Down syndrome or any DNA fragility syndromes such as Bloom's syndrome.
• Autologous hematopoietic stem cell transplant (HSCT) within 6 weeks prior to enrollment
• Allogeneic hematopoietic stem cell transplant (HSCT) within 3 months prior to enrollment
• Any graft-versus-host disease requiring systemic therapy with immunomodulators
• Subjects with history or presence of clinically relevant non-malignant CNS disease requiring treatment (eg, uncontrolled seizures)
• Subjects with clinically relevant or uncontrolled active infections
• History or evidence of significant cardiovascular risk including any of the following: symptomatic congestive heart failure, unstable angina, clinically significant arrhythmias (eg, ventricular fibrillation, ventricular tachycardia etc.), coronary angioplasty within 6 months before dosing, intra-cardiac defibrillators or any clinically relevant concurrent disorder that may pose a risk to subject safety or interfere with study evaluation, procedures, or completion.

Sponsors & Collaborators

• Amgen: lead

Study Sites (3)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Stanford University

Palo Alto, California, 94305, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Neoplasms

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2019
• First Posted: April 4, 2019
• Study Start: March 13, 2023
• Primary Completion (Estimated): August 7, 2030
• Study Completion (Estimated): August 7, 2030
• Last Updated: June 12, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.

Locations

US (3)