A Pilot Study of Dociparstat Sodium (ODSH) in Acute Myeloid Leukemia
Condition: Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Dociparstat sodium
Intervention description: The following induction regimen was administered:
Cytarabine (100 mg/m2/day) via continuous intravenous (IV) infusion 24 hours daily for 7 days.
Idarubicin (12 mg/m2/day) IV on Days 1, 2, and 3.
Dociparstat (4 mg/kg) given over 5 minutes IV, immediately after the idarubicin dose on Day 1, followed by a continuous IV infusion (0.25 mg/kg/hr for 24 hours daily) for a total of 7 days.
Intervention MeSH terms: Heparin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Acute Myeloid Leukemia; AML; ODSH; ODSH-AML; CX-01; dociparstat; dociparstat sodium; 2-O, 3-O desulfated heparin

Summary:

      This was an open-label pilot study that evaluated the safety and preliminary evidence of a
      therapeutic effect of dociparstat in conjunction with standard induction and consolidation
      therapy for acute myeloid leukemia (AML).
    

Eligibility criteria:

        Inclusion Criteria:

        All patients had to meet the following criteria to be eligible for this study:

          1. Had newly diagnosed, previously untreated acute myeloid leukemia (AML). Acute
             promyelocytic leukemia and acute megakaryoblastic leukemia subtypes were excluded

          2. Had no prior chemotherapy for AML; however, prior hydroxyurea to control white blood
             cell count was allowed

          3. Was aged 18 years or older.

          4. Had an Eastern Cooperative Oncology Group (ECOG) Performance status of 0-2.

          5. Had a cardiac ejection fraction ≥ 50% (echocardiography or Multi-Gated Acquisition
             Scan [MUGA]).

          6. Had adequate hepatic and renal function (aspartate aminotransferase [AST], alanine
             aminotransferase [ALT], bilirubin and creatinine < 2.5 x upper normal limit).

          7. 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:

          1. Had acute promyelocytic leukemia.

          2. Had acute megakaryoblastic leukemia.

          3. Had central nervous system (CNS) leukemia

          4. Had the presence of uncontrolled bleeding.

          5. Had the presence of significant active infection that was uncontrolled, as judged by
             the Investigator.

          6. Had a history of severe congestive heart failure or other cardiac disease that
             contraindicated the use of anthracyclines, including idarubicin.

          7. Had pre-existing liver disease.

          8. 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.

          9. Had use of recreational drugs or history of drug addiction, within the prior 6 months.

         10. Had known history of positive hepatitis B surface antigens or hepatitis C virus (HCV)
             antibodies.

         11. Had known history of positive test for human immunodeficiency virus (HIV) antibodies

         12. Had psychiatric or neurologic conditions that could have compromised patient safety or
             compliance, or interfered with the ability to give proper informed consent.

         13. 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.

         14. 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).

         15. Had received any form of anticoagulant therapy.

         16. Had the presence of a known bleeding disorder or coagulation abnormality.

         17. 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).

         18. Were pregnant or breast-feeding patients.

         19. Were of childbearing potential and were not using adequate contraception.

         20. Had any condition that required maintenance of platelet counts at 50,000/μL or higher.