Clinical Trials /

Study of AMV564 in Patients With AML

NCT03144245

Description:

This is a first in human, non randomized, open-label, dose escalation study to investigate the safety, tolerability and preliminary efficacy of AMV564.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of AMV564 in Patients With AML
  • Official Title: A Phase 1, First in Human, Open Label, Dose Escalation Study of AMV564, a CD33 x CD3 Tandem Diabody in Patients With Relapsed or Refractory Acute Myeloid Leukemia

Clinical Trial IDs

  • ORG STUDY ID: AMV564-101
  • NCT ID: NCT03144245

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
AMV564AMV564

Purpose

This is a first in human, non randomized, open-label, dose escalation study to investigate the safety, tolerability and preliminary efficacy of AMV564.

Detailed Description

      This study is a first in human, Phase 1, open label, multicenter, dose escalation study with
      expansion at the RP2D to evaluate the safety, tolerability and preliminary antileukemic
      activity of AMV564 in patients with relapsed or refractory acute myeloid leukemia (AML).

      AMV564 will be given on Days 1-14 of a 4-week cycle, or Days 1-28 of a 6-week cycle,via CIV
      or subcutaneous administration for 1 or more treatment cycles as monotherapy or in
      combination with pembrolizumab.
    

Trial Arms

NameTypeDescriptionInterventions
AMV564ExperimentalContinuous infusion or subcutaneous dosing of AMV564 at increasing dose levels
  • AMV564
Combination AMV564ExperimentalContinuous infusion or subcutaneous dosing of AMV564 at increasing dose levels in combination with pembrolizumab

    Eligibility Criteria

            Inclusion Criteria:
    
              -  ≥ 18 years of age at the time of signing informed consent
    
              -  Diagnosis of AML according to the World Health Organization (WHO) 2008 criteria
    
              -  Relapsed or refractory disease meeting the following criteria:
    
                   1. Primary refractory, ie, refractory to induction with a standard intensive
                      anthracycline/cytarabine-based regimen or a non-intensive regimen (e.g.,
                      decitabine, azacytidine, low-dose cytarabine) for patients ineligible for an
                      intensive anthracycline/cytarabine-based therapy
    
                   2. First untreated relapse after a first CR lasting less than 12 months or first
                      relapse refractory to salvage therapy regardless of length of first CR; or
    
                   3. Second or later relapse. Relapse is defined as the reappearance of leukemic
                      blasts in the peripheral blood or ≥ 5% leukemic blasts in the bone marrow after
                      prior achievement of a CR or CRi.
    
            OR Patients with newly diagnosed therapy-related AML, AML progressed from antecedent MDS or
            CMML treated with hypomethylating agents, or de novo AML with MDS-related cytogenetic
            abnormalities (per 2008 WHO criteria) and who are not candidates for (or decline) intensive
            remission induction therapy
    
              -  No more than 3 prior induction/salvage regimens to treat active disease, and no more
                 than 1 prior stem cell transplant. Any number of continuous cycles of therapy with an
                 individual hypomethylating agent count as one induction or salvage regimen.
    
              -  Blasts at least 5% in bone marrow
    
              -  Peripheral white blood cell (WBC) count: no upper limit at Screening, but must be < 10
                 x 109/L on Day 1 prior to treatment; patients with excessive blasts may be treated
                 with hydroxyurea to bring counts down.
    
              -  Chemistry laboratory parameters within the following range:
    
                   1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2x the
                      upper limit of normal (ULN)
    
                   2. Total bilirubin ≤ 1.5x the ULN; patients with Gilbert's syndrome can enroll if
                      conjugated bilirubin is within normal limits.
    
                   3. Creatinine clearance > 50 mL/min (measured or calculated by Cockcroft-Gault
                      method)
    
              -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients with
                 ECOG score of 2 may be included, after discussion with the Sponsor Medical Monitor, if
                 score is influenced by symptoms attributable to underlying AML disease.
    
              -  Willing to complete all scheduled visits and assessments at the institution
                 administering therapy
    
              -  Able to read, understand and provide written informed consent
    
            Exclusion Criteria:
    
            Patients who meet any of the following criteria will be excluded from the study.
    
              -  History of, or known, central nervous system (CNS) disease involvement, or prior
                 history of National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events
                 (CTCAE) Grade ≥ 3 drug-related CNS toxicity
    
              -  Prior allogeneic transplant (dose escalation only)
    
              -  Prior solid organ transplantation
    
              -  Treatment with anti-thymocyte globulin (ATG) within 14 days prior to start date
    
              -  Treatment with any local or systemic antineoplastic therapy or radiation within 14
                 days prior to the initiation of AMV564 administration (hydroxyurea is exempted if used
                 to reduce total WBC counts)
    
              -  Clinically significant cardiac disease,
    
              -  Pulmonary, renal, hepatic, gastrointestinal, neurological or psychiatric disease that
                 would limit compliance with study requirements
    
              -  Evidence of active, uncontrolled, viral, bacterial, or systemic fungal infection.
                 Prophylactic therapy according to institutional protocols is acceptable.
    
              -  Known positive test result for human immunodeficiency virus (HIV) or acquired immune
                 deficiency syndrome (AIDS)
    
              -  Active hepatitis C virus (HCV) or hepatitis B virus (HBV). Patients who are positive
                 for hepatitis B core antibody, hepatitis B surface antigen, or hepatitis C antibody
                 must have a negative polymerase chain reaction (PCR) result before enrollment. Those
                 who are PCR positive will be excluded.
    
              -  Second primary malignancy that has not been in remission for greater than 3 years.
                 Exceptions that do not require a 3-year remission include: non-melanoma skin cancer;
                 cervical carcinoma in situ on biopsy or squamous intraepithelial lesion on
                 Papanicolaou (PAP) smear; localized prostate cancer (Gleason score < 6); or resected
                 melanoma in situ.
    
              -  Major trauma or major surgery within 28 days prior to the initiation of AMV564
                 treatment
    
              -  Any serious underlying medical or psychiatric condition (e.g. alcohol or drug abuse),
                 dementia or altered mental status or any issue that would impair the ability of the
                 patient to understand informed consent or that in the opinion of the investigator
                 would contraindicate the patient's participation in the study or confound the results
                 of the study.
    
              -  Ability to become pregnant. However, female patients who have a negative serum or
                 urine pregnancy test before enrollment and agree to use two highly effective forms of
                 contraception (oral, injected or implanted hormonal contraception and condom;
                 intrauterine device and condom; diaphragm with spermicidal gel and condom) during the
                 trial and for 90 days afterward (90 days after the end of AMV564 treatment) are
                 considered eligible.
    
              -  Male patients with partners of childbearing potential.
    
              -  Pregnant or breastfeeding women
    
              -  Is a participant or plans to participate in another interventional clinical study,
                 while taking part in this protocol. Participation in an observational study is
                 acceptable.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Dose escalation + expansion stage: incidence of all adverse events and serious adverse events (safety and tolerability)
    Time Frame:42 months
    Safety Issue:
    Description:Number of participants with adverse events as a measure of safety and tolerability.

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Amphivena Therapeutics, Inc.

    Trial Keywords

    • AML
    • treatment
    • relapsed
    • refractory
    • phase 1

    Last Updated

    December 17, 2019