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

Study Overview
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Brief Summary
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Phase 3 study to evaluate the efficacy and safety of dociparstat sodium in adults with newly diagnosed untreated AML with adverse or intermediate genetic risk.

Detailed Description
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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 AML patients.

Official Title
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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

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Dociparastat sodium
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed, previously untreated AML (according to World Health Organization criteria) with at least 20% blasts in the peripheral blood or bone marrow. Age ≥ 18 with Intermediate or Adverse genetic risk (per ELN criteria). Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Exclusion Criteria: Acute promyelocytic leukemia (t(15;17)), myeloid sarcoma without bone marrow involvement, or blast transformation of chronic myelogenous leukemia. Clinical evidence of active central nervous system leukemia. 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. Receiving any form of anticoagulant therapy (e.g., unfractionated heparin, low molecular weight heparin, coumadin, factor Xa inhibitors). Heparin flush of indwelling catheters is permitted. Treatment with any other investigational agent within 28 days, or 5 half-lives, whichever is longer, prior to baseline. Any major surgery or radiation therapy within 28 days prior to baseline. Immediately life threatening, severe complications of leukemia such as pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation. Active or uncontrolled bleeding at the time of randomization; a bleeding disorder, either inherited or caused by disease; history of known arterial-venous malformation, intracranial hemorrhage, or suspected or known cerebral aneurysm; or clinically significant gastrointestinal bleeding within the 3 weeks prior to randomization. Presence of significant active or uncontrolled infection, including HIV or hepatitis B or C. Active (uncontrolled, metastatic) second malignancy. History of severe congestive heart failure or other cardiac disease that contraindicates the use of idarubicin or daunorubicin (e.g., cardiac ejection fraction <45%). QTc >480 msec. Severe renal impairment, as determined by calculated creatinine clearance <30 mL/min or estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3x upper limit of normal (ULN) or total bilirubin >2x ULN.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dociparstat sodium (DSTAT)<br>Treatment with standard intensive induction, reinduction, or consolidation chemotherapy and Dociparstat 4 mg/kg 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: Dociparastat sodium<br>* Dociparstat is a glycosaminoglycan derived from porcine heparin.<br>* Other names: ODSH;|
| Placebo Comparator: Placebo<br>Treatment with standard intensive induction, reinduction, or consolidation chemotherapy and Placebo 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: Placebo<br>* 0.9% Normal Saline<br>* Other names: Sodium chloride 0.9%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival is defined as time until death from any cause, through 5 years. | Measured from randomization up to 5 years | 

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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML