Clinical Trials /

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

NCT03904069

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study Evaluating the Safety, Tolerability, and Efficacy of FLT3 CAR-T AMG 553 in FLT3-positive Relapsed/Refractory AML
  • Official Title: A Phase 1 Study Evaluating the Safety, Tolerability, and Efficacy of FLT3 Chimeric Antigen Receptor T-cell (CAR-T) AMG 553 in Subjects With FLT3-positive Relapsed/Refractory Acute Myeloid Leukemia.

Clinical Trial IDs

  • ORG STUDY ID: 20180091
  • NCT ID: NCT03904069

Conditions

  • Relapsed/Refractory Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
AMG 553Comparison of different cell doses of AMG 553

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Comparison of different cell doses of AMG 553ExperimentalSubjects will receive IV infusion of AMG 553
  • AMG 553

Eligibility Criteria

        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.

        Exclusion Criteria:

          -  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.

          -  History of arterial thrombosis (eg, stroke or transient ischemic attack) within 3
             months prior to enrollment.

          -  History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months
             before enrollment.

          -  Positive test for human immunodeficiency virus (HIV)

          -  Positive for hepatitis B surface antigen (HepBsAg)

          -  Positive for acute or chronic hepatitis C. Exceptions: Acute hepatitis C and
             completely cleared of the virus (demonstrated by negative viral load). Chronic
             hepatitis C with undetectable viral load defined by sustained virologic response 24
             weeks (SVR24) after completion of anti-hepatitis C treatment.

          -  Received live vaccine(s) within 4 weeks of enrollment.

          -  Unresolved toxicities from prior antitumor therapy not having resolved to Common
             Terminology Criteria for Adverse Events (CTCAE), version 5.0 grade 1 with the
             exception of myelosuppression (eg, neutropenia, anemia, thrombocytopenia) or are
             stable and well controlled AND there is agreement to allow by both the investigator
             and sponsor.

          -  Treatment with systemic immune modulators including, but not limited to, non-topical
             systemic corticosteroids, cyclosporine, and tacrolimus within 2 weeks before
             enrollment (exception: low dose systemic corticosteroids if used for blood transfusion
             reactions or similar).

          -  Major surgery within 28 days of enrollment with the exception of biopsy and insertion
             of central venous catheter.

          -  Subject has known sensitivity and immediate hypersensitivity to any components of AMG
             553 or lymphodepleting regimen (cyclophosphamide and fludarabine).

          -  Other anti-cancer therapy (eg, investigational therapy, chemotherapy, antibody
             therapy, molecular targeted therapy) within 14 days (or 5 half-lives, whichever is
             shorter) prior to leukapheresis. Use of immune checkpoint inhibitors is excluded 3
             months prior to leukapheresis.

          -  Prior treatment with any CAR-T or other genetically modified cell therapy.

          -  Presence of any clinically relevant indwelling line or drain (eg, percutaneous
             nephrostomy tube, biliary drain, or pleural/peritoneal/pericardial catheter).

          -  History of autoimmune disease (eg, Crohn's, rheumatoid arthritis, systemic lupus)
             resulting in end organ injury or requiring systemic immunosuppression/systemic disease
             modifying agents within the last 2 years prior to enrollment.

          -  Females of child-bearing potential who are not willing to practice a highly effective
             method(s) of birth control from the time of consent through 6 months after AMG 553
             infusion day.

          -  Females who are pregnant or planning to become pregnant or breastfeeding or who plan
             to breastfeed from the time of consent through 6 months after AMG 553 infusion day.

          -  Males who are unwilling to abstain from sperm donation while on study through 6 months
             after AMG 553 infusion day.

          -  Male subjects with a female partner of childbearing potential who are unwilling to
             practice sexual abstinence (refrain from heterosexual intercourse) or use
             contraception from the time of consent through 6 months after AMG 553 infusion day.

          -  Subject likely to not be available to complete all protocol-required study visits or
             procedures, and/or to comply with all required study procedures to the best of the
             subject and investigator's knowledge.

          -  History or evidence of any other clinically significant disorder, condition or disease
             that, in the opinion of the investigator or Amgen physician, if consulted, would pose
             a risk to subject safety or interfere with the study evaluation, procedures or
             completion.

          -  Subjects with clinically significant pre-existing liver disease, such as cirrhosis
      
Maximum Eligible Age:N/A
Minimum Eligible Age:12 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose limiting toxicities (DLTs)
Time Frame:3 Months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Complete response (CR)
Time Frame:3 months
Safety Issue:
Description:Evidence of anti-leukemic activity of AMG 553
Measure:Complete response with partial recovery of peripheral blood counts (CRh)
Time Frame:3 months
Safety Issue:
Description:Evidence of anti-leukemic activity of AMG 553
Measure:Complete response with incomplete recovery of peripheral blood counts (CRi)
Time Frame:3 months
Safety Issue:
Description:Evidence of anti-leukemic activity of AMG 553
Measure:Morphologic leukemia-free state (MLFS)
Time Frame:3 months
Safety Issue:
Description:Evidence of anti-leukemic activity of AMG 553
Measure:Duration of response (DOR)
Time Frame:3 months
Safety Issue:
Description:Evidence of anti-leukemic activity of AMG 553
Measure:Progression free survival (PFS)
Time Frame:3 months
Safety Issue:
Description:Evidence of anti-leukemic activiy of AMG 553
Measure:Overall Survival (OS)
Time Frame:3 months
Safety Issue:
Description:Evidence of anti-leukemic activity of AMG 553
Measure:Proportion of subjects with minimal-residual disease (MRD) negative response
Time Frame:3 Months
Safety Issue:
Description: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.
Measure:The area under the concentration time-curve (AUC) of AMG 553
Time Frame:3 Months
Safety Issue:
Description:Evaluate the cellular kinetics of AMG 553 post infusion
Measure:Peak levels of AMG 553 (maximum concentration or Cmax)
Time Frame:3 months
Safety Issue:
Description:Evaluate the cellular kinetics of AMG 553 post infusion

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Amgen

Trial Keywords

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

Last Updated