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Relapsed/Refractory Acute Myeloid LeukemiaPhase 1NCT03904069

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

A Phase 1 study testing AMG 553 in people with Relapsed/Refractory Acute Myeloid Leukemia, run by Amgen at 3 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 12 years and older
What is being tested?
AMG 553
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
3 sitesUnited States
Study dates
13 Mar 2023to 7 Aug 2030
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
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  • 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

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • City of Hope National Medical Center

    Duarte, California, 91010

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Stanford University

    Palo Alto, California, 94305

Other trials in United States

About this study

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.

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.

Being tested
AMG 553
Keywords
Relapsed/refractory acute myeloid leukemia, Acute myeloid leukemia, Oncology/hematology, CAR T cell therapy
Medical subject headings
Leukemia, Myeloid, Acute, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AMG 553Drug

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

Study groups in NCT03904069
Study groupRoleWhat they receive
Comparison of different cell doses of AMG 553ExperimentalSubjects will receive IV infusion of AMG 553
Receives: Drug: AMG 553

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose limiting toxicities (DLTs)

    Measured: 3 Months

  2. Treatment-emergent adverse events

    Measured: 3 months

  3. Treatment-related adverse events

    Measured: 3 months

Secondary outcomes (10)

  1. Complete response (CR)

    Evidence of anti-leukemic activity of AMG 553

    Measured: 3 months

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

    Evidence of anti-leukemic activity of AMG 553

    Measured: 3 months

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

    Evidence of anti-leukemic activity of AMG 553

    Measured: 3 months

  4. Morphologic leukemia-free state (MLFS)

    Evidence of anti-leukemic activity of AMG 553

    Measured: 3 months

  5. Duration of response (DOR)

    Evidence of anti-leukemic activity of AMG 553

    Measured: 3 months

  6. Progression free survival (PFS)

    Evidence of anti-leukemic activiy of AMG 553

    Measured: 3 months

  7. Overall Survival (OS)

    Evidence of anti-leukemic activity of AMG 553

    Measured: 3 months

  8. Proportion of subjects with minimal-residual disease (MRD) negative response

    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.

    Measured: 3 Months

  9. The area under the concentration time-curve (AUC) of AMG 553

    Evaluate the cellular kinetics of AMG 553 post infusion

    Measured: 3 Months

  10. Peak levels of AMG 553 (maximum concentration or Cmax)

    Evaluate the cellular kinetics of AMG 553 post infusion

    Measured: 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Apr 2019
  2. Study start13 Mar 2023 (estimated)
  3. Primary completion7 Aug 2030 (estimated)
  4. Study completion7 Aug 2030 (estimated)

Why it stopped: Following a recent cellular therapy strategy assessment, Amgen has decided to cancel study 20180091.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03904069
Sponsor's protocol ID
20180091
Status last verified
Jun 2023
First submitted
21 Mar 2019
Last updated
12 Jun 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AMG 553 in people with Relapsed/Refractory Acute Myeloid Leukemia, run by Amgen at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 12 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose limiting toxicities (DLTs) (time frame: 3 Months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03904069.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2023.

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