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Dociparstat Sodium (CX-01) Combined With Standard Induction Therapy for Newly Diagnosed Acute Myeloid Leukemia

Primary Purpose

Acute Myeloid Leukemia

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Dociparstat sodium
Idarubicin
Cytarabine
Sponsored by
Chimerix
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Newly diagnosed, de novo or secondary, previously untreated AML
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

Exclusion Criteria:

  • Acute promyelocytic leukemia
  • Prior chemotherapy for AML
  • Prior intensive chemotherapy or stem cell transplantation for the treatment of myelodysplastic syndrome
  • CNS leukemia

Sites / Locations

  • University of California, San Diego, Moores Cancer Center
  • Colorado Blood Cancer Institute
  • George Washington University
  • Franciscan St. Francis Health
  • June E. Nylen Cancer Center
  • Norton Cancer Institute
  • Tulane University/Tulane Cancer Center
  • Karmanos Cancer Institute
  • Allina Health - Virginia Piper Cancer Institute
  • Washington University School of Medicine in St. Louis
  • New Mexico Cancer Care Alliance
  • Montefiore Medical Center
  • Northwell Health, Monter Cancer Center
  • University of Cincinnati
  • Oregon Health & Science University Knight Cancer Institute
  • Rhode Island Hospital
  • Medical University of South Carolina
  • Avera Cancer Institute
  • Tennessee Oncology/Sarah Cannon Research Institute
  • Baylor Research Institute/Baylor Sammons Cancer Center/Baylor University Medical Center
  • Methodist Healthcare System of San Antonio
  • Huntsman Cancer Institute
  • LDS Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Experimental

Arm Label

Control (idarubicin+cytarabine)

Dociparstat 0.125 mg/kg

Dociparstat 0.25 mg/kg

Arm Description

Induction: Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) intravenous (IV) injection/infusion daily (Days 1, 2, and 3) Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1 to 7) Re-induction: Idarubicin 12 mg/m2/day slow (10 to 30 minutes) IV injection/infusion daily (Days 1 and 2) Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1 to 5) Consolidation: • Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, and 5)

Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/hr continuous 24-hour intravenous (IV) infusion (Days 1 to 7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, and 3) Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1 to 7) Re-induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/hr continuous 24-hour IV infusion (Days 1 to 5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1 and 2) Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1 to 5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.125 mg/kg/hr continuous 24-hour IV infusion on (Days 1 to 5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, and 5)

Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/hr continuous 24-hour intravenous (IV) infusion (Days 1 to 7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, and 3) Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1 to 7) Re-induction: Dociparstat 4 mg/kg initial bolus 20 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/hr continuous 24-hour IV infusion (Days 1 to 5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1 and 2) Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1 to 5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.25 mg/kg/hr continuous 24-hour IV infusion (Days 1 to 5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, and 5)

Outcomes

Primary Outcome Measures

Number of Subjects Who Achieved Morphologic Complete Remission
Morphologic complete remission (CR) was evaluated by International Working Group (IWG) criteria and defined as absolute neutrophil count (ANC) >1000/microliter; platelet count >100,000, <5% blasts in bone marrow aspirate, no blasts with Auer rods, and no evidence of extramedullary disease.

Secondary Outcome Measures

Duration of Event-free Survival
Event-free survival was measured as date of randomization until treatment failure. Treatment failure was defined as failure to achieve composite completed morphological remission during the induction and re-induction phase of the study lasting up to 60 days, relapse from complete response, or death from any cause, whichever occurred first.
Time to Leukemia-free Survival
Leukemia-free survival was assessed as a secondary endpoint only in subjects who achieved composite complete remission and was measured from randomization until disease relapse or death from any cause, whichever occurred first. Assessments were performed every 3 months until death or 18 months after the last subject was randomized, whichever occurred first.
Number of Subjects Who Achieved Overall Survival
Overall survival was measured from the date of randomization until death from any cause. Assessments were performed every 3 months and continued until death or 18 months after the last patient was randomized, whichever came first.
Number of Subjects Who Achieved Composite Complete Remission
The composite complete remission (CR) rate included CR, CR without recovery of platelets (CRp), and CR without recovery of neutrophils and/or platelets (CRi), as defined by the International Working Group criteria during the induction and re-induction phases of treatment. CR was defined as an Absolute Neutrophil Count (ANC) >1000/μL, platelet count >100,000/μL, <5% blasts in bone marrow aspirate, no blasts with Auer rods, and no evidence of extramedullary disease. CRi was defined as an ANC <1000/μL and/or platelet count <100,000/, <5% blasts in bone marrow aspirate, no blasts with Auer rods, and no evidence of extramedullary disease.
Duration of Morphologic Complete Remission
The duration of morphologic complete remission was assessed only in subjects who had achieved morphologic complete remission and was defined as the time from achievement of complete response to the detection or relapse. Relapse was defined as the reappearance of leukemia blasts in the peripheral blood, >5% blasts in the bone marrow not attributable to another cause, or appearance/reappearance of extramedullary disease and with a bone marrow blast percentage of >5% but ≤20%. If the latter, a repeat bone marrow examination was performed at least 7 days after the first marrow examination; documentation of the bone marrow blast percentage of >5% was necessary to establish relapse. Assessments were performed every 3 months and continued until death or 18 months after the last subject was randomized, whichever occurred first. Duration of morphologic complete remission (time from the achievement of complete response to the detection of relapse)
Time to Recovery of Neutrophils
Neutrophil recovery was assessed from randomization to Absolute Neutrophil Count (ANC) recovery (ANC >500/µL and >1000/µL) for up to 60 days after the start of each treatment cycle.
Time to Platelet Recovery
Platelet recovery was measured from randomization to platelet recovery (platelet count >20,000/µL and >100,000/µL)
Number of Subjects Who Died by Day 30
Mortality (rate of death) of subjects by Day 30, measured from the first day of induction treatment to 30 days post-induction.
Number of Subjects Who Died by Day 60.
Mortality (rate of death) of subjects by Day 60, measured from the first day of induction treatment to 60 days post-induction.
Number of Subjects Who Died by Day 90
Mortality (rate of death) of subjects at Day 90, measured from the first day of induction treatment to 90 days post-induction.

Full Information

First Posted
August 12, 2016
Last Updated
August 29, 2023
Sponsor
Chimerix
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1. Study Identification

Unique Protocol Identification Number
NCT02873338
Brief Title
Dociparstat Sodium (CX-01) Combined With Standard Induction Therapy for Newly Diagnosed Acute Myeloid Leukemia
Official Title
A Randomized, Phase II Study of CX-01 Combined With Standard Induction Therapy for Newly Diagnosed Acute Myeloid Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
August 2016 (Actual)
Primary Completion Date
June 2019 (Actual)
Study Completion Date
June 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Chimerix

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This was an exploratory Phase 2, open label, randomized, multicenter, parallel group study to determine whether there was evidence that the addition of dociparstat (CX-01) at 2 different does levels to standard induction therapy (cytarabine+idarubicin, "7+3") and consolidation therapy had an additive therapeutic effect for subjects newly diagnosed with acute myeloid leukemia (AML) when compared with subjects receiving standard induction chemotherapy alone.
Detailed Description
The primary efficacy endpoint was to assess whether dociparstat in conjunction with standard induction therapy for AML increased the complete remission rate based on the International Working Group AML response criteria. A total of 75 subjects were to be randomized in a 1:1:1 ratio to 1 of the following treatment groups: Group 1: cytarabine + idarubicin Group 2: cytarabine + idarubicin + dociparstat 0.125 mg/kg/hr Group 3: cytarabine + idarubicin + dociparstat 0.25 mg/kg/hr Subjects received up to 2 induction cycles and up to 2 consolidation cycles and participated in the study for up to 18 months. Clinical laboratory tests were conducted routinely, and bone marrow aspirates and biopsies were performed during the induction cycles. Safety was monitored through adverse events and clinical laboratory results.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
75 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Control (idarubicin+cytarabine)
Arm Type
Active Comparator
Arm Description
Induction: Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) intravenous (IV) injection/infusion daily (Days 1, 2, and 3) Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1 to 7) Re-induction: Idarubicin 12 mg/m2/day slow (10 to 30 minutes) IV injection/infusion daily (Days 1 and 2) Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1 to 5) Consolidation: • Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, and 5)
Arm Title
Dociparstat 0.125 mg/kg
Arm Type
Experimental
Arm Description
Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/hr continuous 24-hour intravenous (IV) infusion (Days 1 to 7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, and 3) Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1 to 7) Re-induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/hr continuous 24-hour IV infusion (Days 1 to 5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1 and 2) Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1 to 5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.125 mg/kg/hr continuous 24-hour IV infusion on (Days 1 to 5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, and 5)
Arm Title
Dociparstat 0.25 mg/kg
Arm Type
Experimental
Arm Description
Induction: Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/hr continuous 24-hour intravenous (IV) infusion (Days 1 to 7) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, and 3) Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1 to 7) Re-induction: Dociparstat 4 mg/kg initial bolus 20 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/hr continuous 24-hour IV infusion (Days 1 to 5) Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1 and 2) Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1 to 5) Consolidation: Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.25 mg/kg/hr continuous 24-hour IV infusion (Days 1 to 5; total 120 hours) Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, and 5)
Intervention Type
Drug
Intervention Name(s)
Dociparstat sodium
Other Intervention Name(s)
2-O, 3-O desulfated heparin, ODSH, PGX-100, CX-01, Dociparstat
Intervention Description
Subjects received 4 mg/kg dociparstat intravenous (IV) bolus followed by doses of 0.125 or 0.25 mg/kg/hr dociparstat given on Days 1 through 7 with standard induction therapy, on Days 1 through 5 or 7 with standard re-induction therapy, and on Days 1, 3, and 5 with standard consolidation therapy.
Intervention Type
Drug
Intervention Name(s)
Idarubicin
Other Intervention Name(s)
Idamycin
Intervention Description
Subjects received 12 mg/m2/day idarubicin by slow (10 to 15 minutes) intravenous (IV) injection daily on Days 1, 2 and 3 of induction therapy, and on Days 1 and 2 of re-induction therapy.
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Intervention Description
Subjects received 100 mg/m2/day cytarabine by continuous intravenous (IV) infusion on Days 1 through 7 of induction therapy and on Days 1 through 5 of re-induction therapy. During consolidation therapy, subjected received 1.0 g/m2 cytarabine IV infusion given over 3 hours every 12 hours on Days 1, 3, and 5.
Primary Outcome Measure Information:
Title
Number of Subjects Who Achieved Morphologic Complete Remission
Description
Morphologic complete remission (CR) was evaluated by International Working Group (IWG) criteria and defined as absolute neutrophil count (ANC) >1000/microliter; platelet count >100,000, <5% blasts in bone marrow aspirate, no blasts with Auer rods, and no evidence of extramedullary disease.
Time Frame
During induction and re-induction phases of treatment (up to 60 days after the start of each treatment cycle)
Secondary Outcome Measure Information:
Title
Duration of Event-free Survival
Description
Event-free survival was measured as date of randomization until treatment failure. Treatment failure was defined as failure to achieve composite completed morphological remission during the induction and re-induction phase of the study lasting up to 60 days, relapse from complete response, or death from any cause, whichever occurred first.
Time Frame
Randomization up to 30 months
Title
Time to Leukemia-free Survival
Description
Leukemia-free survival was assessed as a secondary endpoint only in subjects who achieved composite complete remission and was measured from randomization until disease relapse or death from any cause, whichever occurred first. Assessments were performed every 3 months until death or 18 months after the last subject was randomized, whichever occurred first.
Time Frame
Randomization until disease relapse or patient death from any cause, whichever occurs first, assessed up to 30 months
Title
Number of Subjects Who Achieved Overall Survival
Description
Overall survival was measured from the date of randomization until death from any cause. Assessments were performed every 3 months and continued until death or 18 months after the last patient was randomized, whichever came first.
Time Frame
Randomization to end of study (18 months)
Title
Number of Subjects Who Achieved Composite Complete Remission
Description
The composite complete remission (CR) rate included CR, CR without recovery of platelets (CRp), and CR without recovery of neutrophils and/or platelets (CRi), as defined by the International Working Group criteria during the induction and re-induction phases of treatment. CR was defined as an Absolute Neutrophil Count (ANC) >1000/μL, platelet count >100,000/μL, <5% blasts in bone marrow aspirate, no blasts with Auer rods, and no evidence of extramedullary disease. CRi was defined as an ANC <1000/μL and/or platelet count <100,000/, <5% blasts in bone marrow aspirate, no blasts with Auer rods, and no evidence of extramedullary disease.
Time Frame
Up to 60 days after the start of each treatment cycle
Title
Duration of Morphologic Complete Remission
Description
The duration of morphologic complete remission was assessed only in subjects who had achieved morphologic complete remission and was defined as the time from achievement of complete response to the detection or relapse. Relapse was defined as the reappearance of leukemia blasts in the peripheral blood, >5% blasts in the bone marrow not attributable to another cause, or appearance/reappearance of extramedullary disease and with a bone marrow blast percentage of >5% but ≤20%. If the latter, a repeat bone marrow examination was performed at least 7 days after the first marrow examination; documentation of the bone marrow blast percentage of >5% was necessary to establish relapse. Assessments were performed every 3 months and continued until death or 18 months after the last subject was randomized, whichever occurred first. Duration of morphologic complete remission (time from the achievement of complete response to the detection of relapse)
Time Frame
Randomization to end of study (18 months)
Title
Time to Recovery of Neutrophils
Description
Neutrophil recovery was assessed from randomization to Absolute Neutrophil Count (ANC) recovery (ANC >500/µL and >1000/µL) for up to 60 days after the start of each treatment cycle.
Time Frame
Randomization to ANC recovery, for up to 60 days after the start of each treatment cycle
Title
Time to Platelet Recovery
Description
Platelet recovery was measured from randomization to platelet recovery (platelet count >20,000/µL and >100,000/µL)
Time Frame
Randomization to platelet recovery, for up to 60 days after the start of each treatment cycle
Title
Number of Subjects Who Died by Day 30
Description
Mortality (rate of death) of subjects by Day 30, measured from the first day of induction treatment to 30 days post-induction.
Time Frame
30 days (from first day of induction treatment to 30 days after)
Title
Number of Subjects Who Died by Day 60.
Description
Mortality (rate of death) of subjects by Day 60, measured from the first day of induction treatment to 60 days post-induction.
Time Frame
60 days (from the first day of induction treatment to 60 days after)
Title
Number of Subjects Who Died by Day 90
Description
Mortality (rate of death) of subjects at Day 90, measured from the first day of induction treatment to 90 days post-induction.
Time Frame
90 days (from the first day of induction treatment to 90 days after)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects had to meet all the following criteria to be eligible for enrollment in this study: Had newly diagnosed, de novo or secondary, previously untreated acute myeloid leukemia (AML). Had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Exclusion Criteria: Subjects who met any of the following criteria were not eligible for enrollment in this study: Had acute promyelocytic leukemia Had prior chemotherapy for AML. Had prior intensive chemotherapy or stem cell transplantation for the treatment of myelodysplastic syndrome. Had central nervous system (CNS) leukemia.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephen Marcus, MD
Organizational Affiliation
Cantex Pharmaceuticals Inc.
Official's Role
Study Director
Facility Information:
Facility Name
University of California, San Diego, Moores Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Colorado Blood Cancer Institute
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
George Washington University
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20037
Country
United States
Facility Name
Franciscan St. Francis Health
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46237
Country
United States
Facility Name
June E. Nylen Cancer Center
City
Sioux City
State/Province
Iowa
ZIP/Postal Code
51101
Country
United States
Facility Name
Norton Cancer Institute
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40207
Country
United States
Facility Name
Tulane University/Tulane Cancer Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Allina Health - Virginia Piper Cancer Institute
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55407
Country
United States
Facility Name
Washington University School of Medicine in St. Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
New Mexico Cancer Care Alliance
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Northwell Health, Monter Cancer Center
City
Lake Success
State/Province
New York
ZIP/Postal Code
11042
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Oregon Health & Science University Knight Cancer Institute
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Avera Cancer Institute
City
Sioux Falls
State/Province
South Dakota
ZIP/Postal Code
57105
Country
United States
Facility Name
Tennessee Oncology/Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Baylor Research Institute/Baylor Sammons Cancer Center/Baylor University Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Methodist Healthcare System of San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Huntsman Cancer Institute
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
LDS Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84143
Country
United States

12. IPD Sharing Statement

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Dociparstat Sodium (CX-01) Combined With Standard Induction Therapy for Newly Diagnosed Acute Myeloid Leukemia

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