Dociparstat Sodium (CX-01) Combined With Standard Induction Therapy for Newly Diagnosed Acute Myeloid Leukemia
- Conditions
- Acute Myeloid Leukemia
- Interventions
- Registration Number
- NCT02873338
- Lead Sponsor
- Chimerix
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 75
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.
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Control (idarubicin+cytarabine) Idarubicin 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) Control (idarubicin+cytarabine) Cytarabine 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) Dociparstat 0.25 mg/kg Idarubicin 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) Dociparstat 0.25 mg/kg Cytarabine 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) Dociparstat 0.125 mg/kg Idarubicin 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) Dociparstat 0.25 mg/kg Dociparstat sodium 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) Dociparstat 0.125 mg/kg Cytarabine 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) Dociparstat 0.125 mg/kg Dociparstat sodium 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)
- Primary Outcome Measures
Name Time Method Number of Subjects Who Achieved Morphologic Complete Remission During induction and re-induction phases of treatment (up to 60 days after the start of each treatment cycle) 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
Name Time Method Duration of Event-free Survival Randomization up to 30 months 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 Randomization until disease relapse or patient death from any cause, whichever occurs first, assessed up to 30 months 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 Randomization to end of study (18 months) 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 Up to 60 days after the start of each treatment cycle 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 to Recovery of Neutrophils Randomization to ANC recovery, for up to 60 days after the start of each treatment cycle 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.
Duration of Morphologic Complete Remission Randomization to end of study (18 months) 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 Platelet Recovery Randomization to platelet recovery, for up to 60 days after the start of each treatment cycle 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 30 days (from first day of induction treatment to 30 days after) 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. 60 days (from the first day of induction treatment to 60 days after) 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 90 days (from the first day of induction treatment to 90 days after) Mortality (rate of death) of subjects at Day 90, measured from the first day of induction treatment to 90 days post-induction.
Trial Locations
- Locations (23)
Franciscan St. Francis Health
🇺🇸Indianapolis, Indiana, United States
Baylor Research Institute/Baylor Sammons Cancer Center/Baylor University Medical Center
🇺🇸Dallas, Texas, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
University of California, San Diego, Moores Cancer Center
🇺🇸La Jolla, California, United States
George Washington University
🇺🇸Washington, District of Columbia, United States
Washington University School of Medicine in St. Louis
🇺🇸Saint Louis, Missouri, United States
New Mexico Cancer Care Alliance
🇺🇸Albuquerque, New Mexico, United States
Northwell Health, Monter Cancer Center
🇺🇸Lake Success, New York, United States
Avera Cancer Institute
🇺🇸Sioux Falls, South Dakota, United States
June E. Nylen Cancer Center
🇺🇸Sioux City, Iowa, United States
Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Tulane University/Tulane Cancer Center
🇺🇸New Orleans, Louisiana, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Allina Health - Virginia Piper Cancer Institute
🇺🇸Minneapolis, Minnesota, United States
Oregon Health & Science University Knight Cancer Institute
🇺🇸Portland, Oregon, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Tennessee Oncology/Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Methodist Healthcare System of San Antonio
🇺🇸San Antonio, Texas, United States
LDS Hospital
🇺🇸Salt Lake City, Utah, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States