Dociparstat in Combination With Standard Chemotherapy for the Treatment of Acute Myeloid Leukemia (AML)

A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Dociparstat Sodium in Combination With Standard Chemotherapy for the Treatment of Newly Diagnosed Acute Myeloid Leukemia

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.

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Dociparstat; Other: Control

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • UC Irvine Medical Center
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Cancer Center
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Norton Cancer Institute, St. Matthews Campus
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University School of Medicine
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Allina Health System / Virginia Piper Cancer Institute
  • New York
    • Hawthorne, New York, United States, 10595
      • New York Medical College
    • New York, New York, United States, 10029
      • Mount Sanai School of Medicine
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • East Carolina University Vidant Medical Center
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Gibbs Cancer Center
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah / Huntsman Cancer Institute
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dociparstat; Treatment with standard intensive induction, reinduction, or consolidation chemotherapy and dociparstat 4 mg/kg intravenous (IV) bolus on Day 1, administered 30 minutes after completion of the first dose of idarubicin or daunorubicin, followed by dociparstat 0.25 mg/kg/hr via continuous IV infusion 24 hours daily for 5 or 7 days.	Drug: Dociparstat; Dociparstat is a glycosaminoglycan derived from porcine heparin.; Other Names: ODSH; DSTAT; CX-01; 2-0,3-0 desulfated heparin; dociparstat sodium
Placebo Comparator: Control; Treatment with standard intensive induction, reinduction, or consolidation chemotherapy and placebo intravenous (IV) bolus on Day 1, administered 30 minutes after completion of the first dose of idarubicin or daunorubicin, followed by placebo via continuous IV infusion 24 hours daily for 5 or 7 days.	Other: Control; 0.9% Normal Saline; Other Names: Normal saline; 0.9% Normal Saline; Sodium chloride 0.9%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival was defined for all study participants through 5 years after randomization. Overall survival was to be measured from the date of randomization to the date of death from any cause. Participants not known to have died at last follow-up contact were to be censored on the date they were last known to be alive. Due to early termination, subjects did not complete long term follow-up and efficacy (including overall survival outcome) was not analyzed.	Measured from randomization to date of death from any cause, up to 1 year.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event free survival	Event free survival (EFS) is defined as time to induction/reinduction treatment failure (within 42 days), relapse after complete remission (CR), or death from any cause.	Measured from randomization up to 5 years

Collaborators and Investigators

• Sponsor: Chimerix

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2021
• Primary Completion (Actual): May 16, 2022
• Study Completion (Actual): May 16, 2022

Study Registration Dates

• First Submitted: September 25, 2020
• First Submitted That Met QC Criteria: September 30, 2020
• First Posted (Actual): October 1, 2020

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: AML
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin
• Other Study ID Numbers: CMX-DS-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No