A Phase 2, Open Label, Ascending Dose Study of ACE-536 for the Treatment of Anemia in Patients With Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS)
1. Documented diagnosis of idiopathic/de novo MDS or non-proliferative chronic
myelomonocytic leukemia (CMML), according to WHO criteria, that meets International
Prognostic Scoring System (IPSS) classification of low or intermediate-1 risk disease
as determined by microscopic and standard cytogenetic analyses of the bone marrow and
peripheral complete blood count (CBC) obtained during screening.
- For non-transfusion dependent patients defined as mean hemoglobin concentration
< 10.0 g/dL of 2 measurements (not influenced by RBC transfusion within 7 days
of measurement) and having received < 4 units of RBCs within 8 weeks prior to
Cycle 1 Day 1), OR,
- For transfusion-dependent defined as having received ≥ 4 units of RBCs for
hemoglobin ≤ 9.0 g/dL within 8 weeks prior to Cycle 1 Day 1.
3. Serum erythropoietin level > 500 U/L, OR, if ≤ 500 U/L, patient is non-responsive to,
refractory to, or intolerant of erythropoiesis-stimulating agents (ESAs), or ESAs are
contraindicated or unavailable.
4. No alternative treatment options, per applicable MDS guidelines, are available and/or
appropriate for the patient, at the discretion of the investigator.
5. ECOG performance status of 0, 1, or 2 (if related to anemia).
6. Adequate renal (creatinine ≤ 2 x upper limit of normal [ULN]) and hepatic (total
bilirubin < 2 x ULN and AST and ALT < 3 x ULN) function.
7. Adequate transferrin saturation (≥ 15%), ferritin (≥ 50 µg/L), folate (≥ 4.5 nmol/L
[≥ 2.0 µg/L]) and vitamin B12 (≥ 148 pmol/L [≥ 200 pg/mL]) during screening
(supplementation and retest during screening is acceptable).
8. Females of child bearing potential (defined as sexually mature women who have not
undergone hysterectomy or bilateral oophorectomy, or are not naturally postmenopausal
≥ 24 consecutive months) must have negative urine or blood pregnancy test prior to
enrollment and use adequate birth control methods (abstinence, oral contraceptives,
barrier method with spermicide, or surgical sterilization) during study
participation. Males must agree to use a latex condom during any sexual contact with
females of child-bearing potential while participating in the study and for 12 weeks
following the last dose of ACE 536, even if he has undergone a successful vasectomy.
Patients must be counseled concerning measures to be used to prevent pregnancy and
potential toxicities prior to the first dose of ACE-536.
9. Patients are able to adhere to the study visit schedule, understand and comply with
all protocol requirements.
10. Patients understand and are able to provide written informed consent.
Key Exclusion Criteria:
1. Prior treatment with azacitidine or decitabine.
2. Treatment within 28 days prior to Cycle 1 Day 1 with:
i) Erythropoiesis stimulating agent (ESA), ii) Granulocyte colony-stimulating factor
(G-CSF) and granulocyte- macrophage colony stimulating factor (GM-CSF), iii)
3. Iron chelation therapy if initiated within 56 days prior to Cycle 1 Day 1.
4. Treatment with another investigational drug or device, or approved therapy for
investigational use ≤ 28 days prior to Cycle 1 Day 1, or if the half-life of the
previous product is known, within 5 times the half-life prior to Cycle 1 Day 1,
whichever is longer.
5. Major surgery within 28 days prior to Cycle 1 Day 1. Patients must have completely
recovered from any previous surgery prior to Cycle 1 Day 1.
6. Platelet count < 30 x 109/L.
7. Any active infection requiring parenteral antibiotic therapy within 28 days prior to
Cycle 1 Day 1 or oral antibiotics within 14 days of Cycle 1 Day 1.
8. History of stroke, deep venous thrombosis (DVT) or arterial embolism within 6 months
prior to Cycle 1 Day 1.
9. Known positive for human immunodeficiency virus (HIV), active infectious hepatitis B
(HBV) or active infectious hepatitis C (HCV).
10. Any malignancy other than MDS which has not been in remission and/or has required
systemic therapy including radiation, chemotherapy, hormonal therapy or surgery,
within the last year prior to Cycle 1 Day 1.
11. Uncontrolled hypertension, defined as systolic blood pressure (BP) ≥ 150 mm Hg or
diastolic BP ≥ 100 mm Hg.
12. Pregnant or lactating females.
13. History of severe allergic or anaphylactic reactions or hypersensitivity to
recombinant proteins or excipients in the investigational drug.
14. Any other condition not specifically noted above which, in the judgment of the
investigator, would preclude the patient from participating in the study.