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

NCT04571645 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: CMX-DS-003
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 14

Brief Summary

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.

Conditions

Acute Myeloid Leukemia

Keywords

AML

Outcome Measures

Primary Outcomes (1)

• 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.

Study Arms (2)

Dociparstat

EXPERIMENTAL

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

Control

PLACEBO COMPARATOR

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

Interventions

Dociparstat DRUG

Dociparstat is a glycosaminoglycan derived from porcine heparin.

Also known as: DSTAT, CX-01, 2-0,3-0 desulfated heparin, ODSH, dociparstat sodium

Dociparstat

Control OTHER

0.9% Normal Saline

Also known as: 0.9% Normal Saline, Normal saline, Sodium chloride 0.9%

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A potential participant must have met all the following criteria to be eligible to participate in the study:
• 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.
• Was aged ≥18 years.
• 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
• 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)

You may not qualify if:

• A potential participant who met any of the follow criteria was not eligible to participate in the study:
• Had acute promyelocytic leukemia (t(15;17)), myeloid sarcoma without bone marrow involvement, or blast transformation of chronic myelogenous leukemia.
• Not applicable (criterion removed in Amendment 1 of the Clinical Study Protocol).
• Not applicable (criterion removed in Amendment 1 of the Clinical Study Protocol).
• Had clinical evidence of central nervous system leukemia.
• Prior/Concomitant Therapy:
• 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.
• 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.
• Received treatment with any other investigational agent within 28 days or 5 half-lives, whichever was longer, prior to baseline.
• Underwent any major surgery or radiation therapy within 28 days prior to baseline.
• Medical conditions:
• Had immediately life threatening, severe complications of leukemia such as pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.
• 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.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (14)

UC Irvine Medical Center

Orange, California, 92868, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Norton Cancer Institute, St. Matthews Campus

Louisville, Kentucky, 40207, United States

Location

Tulane University School of Medicine

New Orleans, Louisiana, 70112, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Allina Health System / Virginia Piper Cancer Institute

Minneapolis, Minnesota, 55407, United States

Location

New York Medical College

Hawthorne, New York, 10595, United States

Location

Mount Sanai School of Medicine

New York, New York, 10029, United States

Location

East Carolina University Vidant Medical Center

Greenville, North Carolina, 27834, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Spartanburg Medical Gibbs Cancer Center

Spartanburg, South Carolina, 29303, United States

Location

Baylor

Dallas, Texas, 75246, United States

Location

University of Utah / Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22903, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Saline Solution; Sodium Chloride

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

Due to low subject accrual, study enrollment was prematurely terminated on 16 May 2021. Therefore, formal statistical analyses were not performed, and no conclusions can be drawn about dociparstat with regards to efficacy.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Chimerix, Inc.

dmoore@chimerix.com

919-806-1074

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2020
• First Posted: October 1, 2020
• Study Start: April 30, 2021
• Primary Completion: May 16, 2022
• Study Completion: May 16, 2022
• Last Updated: April 15, 2024
• Results First Posted: April 15, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)