A Pilot Study of Dociparstat Sodium (ODSH) in Acute Myeloid Leukemia

Inclusion Criteria

All patients had to meet the following criteria to be eligible for this study:

• Had newly diagnosed, previously untreated acute myeloid leukemia (AML). Acute promyelocytic leukemia and acute megakaryoblastic leukemia subtypes were excluded
• Had no prior chemotherapy for AML; however, prior hydroxyurea to control white blood cell count was allowed
• Was aged 18 years or older.
• Had an Eastern Cooperative Oncology Group (ECOG) Performance status of 0-2.
• Had a cardiac ejection fraction ≥ 50% (echocardiography or Multi-Gated Acquisition Scan [MUGA]).
• Had adequate hepatic and renal function (aspartate aminotransferase [AST], alanine aminotransferase [ALT], bilirubin and creatinine < 2.5 x upper normal limit).
• Was able to provide informed consent and signed an approved consent form that conformed to federal and institutional guidelines.

Exclusion Criteria

Patients who met any of the following criteria were not eligible to be enrolled in this study:

• Had acute promyelocytic leukemia.
• Had acute megakaryoblastic leukemia.
• Had central nervous system (CNS) leukemia
• Had the presence of uncontrolled bleeding.
• Had the presence of significant active infection that was uncontrolled, as judged by the Investigator.
• Had a history of severe congestive heart failure or other cardiac disease that contraindicated the use of anthracyclines, including idarubicin.
• Had pre-existing liver disease.
• Had renal insufficiency, which, in the opinion of the Investigator, might have adversely affected the schedule and dose of therapy with cytarabine, as well as the management of tumor lysis syndrome. Patients with creatinine levels ≥2 mg/dL were not eligible.
• Had use of recreational drugs or history of drug addiction, within the prior 6 months.
• Had known history of positive hepatitis B surface antigens or hepatitis C virus (HCV) antibodies.
• Had known history of positive test for human immunodeficiency virus (HIV) antibodies
• Had psychiatric or neurologic conditions that could have compromised patient safety or compliance, or interfered with the ability to give proper informed consent.
• Had history of other active malignant disease within 5 years, other than cured basal cell carcinoma of the skin, cured in situ carcinoma of the cervix, or localized prostate cancer that had received definitive therapy. Such prostate cancer patients who were receiving hormonal therapy were eligible.
• Had the presence of disseminated intravascular coagulation, as confirmed by laboratory studies demonstrating evidence of both increased thrombin generation (decreased fibrinogen, prolonged prothrombin time [PT] and partial thromboplastin time [aPTT]), as well as increased fibrinolysis (elevated D-dimer level).
• Had received any form of anticoagulant therapy.
• Had the presence of a known bleeding disorder or coagulation abnormality.
• Had received treatment with any other investigational agent within 7 days prior to study entry. All prior toxicities should have been resolved to no greater than Grade 1 (with the exception of alopecia).
• Were pregnant or breast-feeding patients.
• Were of childbearing potential and were not using adequate contraception.
• Had any condition that required maintenance of platelet counts at 50,000/μL or higher.