Study enrollment was terminated on 16 May 2022 due to slow recruitment.

Phase 3 study to evaluate the efficacy and safety of dociparstat sodium in adults with newly diagnosed untreated acute myeloid leukemia (AML) with adverse or intermediate genetic risk.

A Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of dociparstat sodium in combination with standard intensive induction and consolidation chemotherapy for the treatment of newly-diagnosed acute myeloid leukemia (AML) patients.

Inclusion Criteria:

A potential participant must have met all the following criteria to be eligible to participate in the study:

1. Had newly-diagnosed, previously untreated acute myeloid leukemia (AML) (according to the World Health Organization criteria) with at least 20% blasts in the peripheral blood or bone marrow.

2. Was aged ≥18 years.

   1. Adverse genetic risk (according to European LeukemiaNet [ELN] criteria), defined as nay of the following genetic abnormalities:

      • t(6;9)(p23;q34.1); DEK-NUP214
      • - t(v;11q23.3); KMT2A rearranged
      • - t(9;22)(q34.1;q11.2); BCR-ABL1
      • - inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOM(EVI1)
      • - -5 or del(5q); -7; -17/abn(17p)
      • - Complex karyotype, monosomal karyotype
      • - Wild-type NPM1 and FLT3-ITDhigh
      • - Mutated RUNX1, mutated ASXL1, or mutated TP53 OR

   2. Intermediate genetic risk (according to ELN criteria), defined as any of the following genetic abnormalities:

      • Mutated NPM1 and FLT3-ITDhigh
      • - Wild-type NPM1 without FLT3-ITD or with FLT3-ITDlow (without adverse-risk genetic lesions)
      • - t(9;11)(p21.3;q23.3); MLLT3-KMT2A
      • - Cytogenetic abnormalities not classified as favorable or adverse

3. Had an Eastern Cooperative Oncology Group performance status of 0 to 2.

4. Provided written informed consent to participate in the study.

Exclusion Criteria:

A potential participant who met any of the follow criteria was not eligible to participate in the study:

Leukemia exclusions:

1. Had acute promyelocytic leukemia (t(15;17)), myeloid sarcoma without bone marrow involvement, or blast transformation of chronic myelogenous leukemia.

2. Not applicable (criterion removed in Amendment 1 of the Clinical Study Protocol).

3. Not applicable (criterion removed in Amendment 1 of the Clinical Study Protocol).

4. Had clinical evidence of central nervous system leukemia.

   Prior/Concomitant Therapy:

5. Had previously received AML treatment, including Vyxeos (CPX-351, liposomal cytarabine and daunorubicin), gemtuzumab ozogamicin, or any other prohibited concomitant AML therapy previously received or anticipated to start during the study.

   Note: Prior hydroxyurea and emergency leukapheresis to control white blood cell count were allowed. All-trans retinoic acid during workup and a single dose of intrathecal cytarabine and/or methotrexate was permitted for participants who were undergoing lumbar puncture to evaluate central nervous system involvement.

6. Were receiving any form of anticoagulant therapy (e.g., unfractionated heparin, low molecular weight heparin, coumadin, factor Xa inhibitors).

   Note: Heparin flush of indwelling catheters was permitted.

7. Received treatment with any other investigational agent within 28 days or 5 half-lives, whichever was longer, prior to baseline.

8. Underwent any major surgery or radiation therapy within 28 days prior to baseline.

   Medical conditions:

9. Had immediately life threatening, severe complications of leukemia such as pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.

10. Had active or uncontrolled bleeding at the time of randomization; a bleeding disorder, either inherited or caused by disease; a history of known arterial-venous malformation, intracranial hemorrhage, or suspected or known cerebral aneurysm; or clinically significant (in the judgement of the Investigator) gastrointestinal bleeding within 3 weeks prior to randomization.

11. Had the presence of significant active or uncontrolled infection, including human immunodeficiency virus (HIV) or hepatitis B or C.

    Note: Subjects with an infection who were receiving treatment (antibiotic, antifungal, or antiviral treatment) may have entered into the study but must have been afebrile and hemodynamically stable for ≥72 hours. Patients who had current evidence of invasive fungal infection (positive blood or tissue culture) must have had subsequent negative cultures to be eligible.

12. Had active (uncontrolled, metastatic) second malignancy. Note: A second malignancy that was in remission was permitted if there was clinical evidence of disease stability for a period of greater than 6 months off cytotoxic chemotherapy that was documented by imaging, tumor marker studies, etc. Long-term nonchemotherapy treatment (e.g., hormonal therapy) was acceptable.

13. Had psychiatric or neurological conditions that could have compromised participant safety or compliance.

14. Had a history of severe congestive heart failure or other cardiac disease that contraindicated the use of idarubicin or daunorubicin (e.g., cardiac ejection fraction <45%, as determined by echocardiography or multigated acquisition scan).

    Diagnostic assessments:

15. Had a corrected QT interval >480 msec.

16. Had severe renal impairment, as determined by calculated creatinine clearance <30 mL/min or estimated glomerular filtration rate <30 mL/min/1.73 m2.

17. Had alanine aminotransferase or aspartate aminotransferase >3x the upper limit of normal (ULN) or total bilirubin >2x the ULN.

    Other:

18. Was a woman of childbearing potential who was pregnant, breastfeeding, and/or not using a highly effective method of contraception (consistent with local regulations regarding the methods of contraception for those participating in clinical studies).

19. Had a history of allergy or hypersensitivity to heparin, pork, or any excipients in the dociparstat formulation.

20. Had any other condition, including abnormal laboratory values that, in the judgement of the Investigator, could have put the participant at increased risk or interfered with the conduct or planned analyses of the study.

Within 18 months of the completion of the Study at all sites, if no publication of the overall multi-center results has been made, institutions are entitled to publish their locally obtained results, provided the Sponsor is given opportunity to review and comment. Institution publications may be delayed up to an additional 60 days to allow Sponsor to seek patent protection.