| Eligibility |
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.
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