A Study of Aezea® (Cenersen) in Transfusion Dependent Anemia Associated With Myelodysplastic Syndrome (MDS)

Inclusion Criteria:

• Must have histologically or cytologically confirmed diagnosis of MDS according to WHO classification that meets IPSS low to intermediate-1 risk criteria.
• For patients with del(5q) MDS, documented del(5q) MDS by metaphase cytogenetics or FISH analysis with up to 1 additional cytogenetic abnormality other than 1 involving chromosome 7 or chromosome 17.
• Demonstrated refractoriness or intolerance to standard approved therapy (lenalidomide in del(5q) MDS patients & azanucleosides in non-del(5q)patients).
• Recovered from acute toxicities of other treatments (≤ Grade 2). All other MDS treatments discontinued at least 4 weeks prior to treatment except epoetin alpha (Procrit) 2 weeks.
• Ability to understand & willingness to sign a written informed consent document.
• Age ≥ 18 years at time of signing informed consent form.
• ECOG performance status ≤2.
• Life expectancy >4 weeks following initiation.

• Must meet following requirements:

  • total bilirubin: ≤2 x upper normal limit (UNL) (patients with Gilbert's disease are eligible, hyperbilirubinemia is intermittent & indirect)
  • AST(SGOT)/ALT(SGPT): ≤3 x UNL
  • creatinine: ≤2 x UNL
• <1% peripheral blood blasts.
• <10% bone marrow blasts.
• Medical history of RBC transfusion dependent anemia ≥4 units of RBCs during the 16 weeks prior to admin of study drug & ≥2 units of RBCs over prior 8 weeks (day -56 to day 1 prior to treatment; baseline period) for documented Hgb of ≤ 9g/dL (during baseline). Didn't have a 56 day RBC transfusion-free period during 16 weeks prior to administration of study drug.
• Teratogenic effects of cenersen are unknown, women of child-bearing potential & men must agree to use adequate contraception prior to study entry & for the duration of study participation.

Exclusion Criteria:

• Receiving MDS treatment except blood transfusion and/or iron chelation within 4 weeks prior to entering study or no recovery from adverse events due to agents administered more than 4 weeks earlier.
• no current or prior use of investigational agents within 4 weeks of study entry.
• Known history of malignancy diagnosed within 2 years other than non-melanoma skin cancer.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to cenersen.
• exclude use of acetaminophen or acetaminophen-containing medications from 1 day before to 1 day after completion of treatment. The active metabolite of acetaminophen, N-acetyl-p-benzoquinone imine (NAPQI), is known to block effects of cenersen & use of acetaminophen during treatment with study regimen has been associated with a failure to achieve a response in a past clinical trial of cenersen.
• Uncontrolled intercurrent illness that would limit compliance with study requirements.
• Pregnant women are excluded from this study. Breastfeeding should be discontinued if the mother is treated with cenersen
• HIV-positive patients on combination antiretroviral therapy are ineligible because of unknown potential for interactions with cenersen.
• Any condition, including presence of laboratory abnormalities, which places subject at unacceptable risk if s/he were to participate in study or confounds ability to interpret data from study according to investigator assessment.
• Therapy related MDS.
• Clinically significant anemia according to investigator's assessment due to factors such as iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis or gastrointestinal bleeding.
• Received hematopoietic growth factors within specified limits prior to treatment (2 weeks for epoetin alpha (Procrit) & 4 weeks for darbepoetin alpha (Aranesp)).
• Active hepatitis B or C or other active liver disease.
• Chronic use (>2 weeks) of greater than physiologic doses of corticosteroid agent (dose equivalent to ≥10mg of prednisone) within 28 days of 1st day of study drug treatment & during treatment