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.
Brief Title
Dociparstat Sodium (CX-01) Combined With Standard Induction Therapy for Newly Diagnosed Acute Myeloid Leukemia
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.
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Acute Myeloid Leukemia
Eligibility Criteria
Inclusion Criteria:
Subjects had to meet all the following criteria to be eligible for enrollment in this study:
1. Had newly diagnosed, de novo or secondary, previously untreated acute myeloid leukemia (AML).
2. 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:
1. Had acute promyelocytic leukemia
2. Had prior chemotherapy for AML.
3. Had prior intensive chemotherapy or stem cell transplantation for the treatment of myelodysplastic syndrome.
4. Had central nervous system (CNS) leukemia.
Subjects had to meet all the following criteria to be eligible for enrollment in this study:
1. Had newly diagnosed, de novo or secondary, previously untreated acute myeloid leukemia (AML).
2. 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:
1. Had acute promyelocytic leukemia
2. Had prior chemotherapy for AML.
3. Had prior intensive chemotherapy or stem cell transplantation for the treatment of myelodysplastic syndrome.
4. Had central nervous system (CNS) leukemia.
Inclusion Criteria
Inclusion Criteria:
Subjects had to meet all the following criteria to be eligible for enrollment in this study:
1. Had newly diagnosed, de novo or secondary, previously untreated acute myeloid leukemia (AML).
2. Had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
Subjects had to meet all the following criteria to be eligible for enrollment in this study:
1. Had newly diagnosed, de novo or secondary, previously untreated acute myeloid leukemia (AML).
2. Had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
60 Years
NCT Id
NCT02873338
Org Class
Industry
Org Full Name
Chimerix
Org Study Id
CNTX-CX-01-2015-AML-1
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Randomized, Phase II Study of CX-01 Combined With Standard Induction Therapy for Newly Diagnosed Acute Myeloid Leukemia
Primary Outcomes
Outcome 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.
Outcome Measure
Number of Subjects Who Achieved Morphologic Complete Remission
Outcome Time Frame
During induction and re-induction phases of treatment (up to 60 days after the start of each treatment cycle)
Secondary Outcomes
Outcome 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.
Outcome Time Frame
Randomization up to 30 months
Outcome Measure
Duration of Event-free Survival
Outcome 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.
Outcome Time Frame
Randomization until disease relapse or patient death from any cause, whichever occurs first, assessed up to 30 months
Outcome Measure
Time to Leukemia-free Survival
Outcome 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.
Outcome Time Frame
Randomization to end of study (18 months)
Outcome Measure
Number of Subjects Who Achieved Overall Survival
Outcome 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.
Outcome Time Frame
Up to 60 days after the start of each treatment cycle
Outcome Measure
Number of Subjects Who Achieved Composite Complete Remission
Outcome 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)
Duration of morphologic complete remission (time from the achievement of complete response to the detection of relapse)
Outcome Time Frame
Randomization to end of study (18 months)
Outcome Measure
Duration of Morphologic Complete Remission
Outcome 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.
Outcome Time Frame
Randomization to ANC recovery, for up to 60 days after the start of each treatment cycle
Outcome Measure
Time to Recovery of Neutrophils
Outcome Description
Platelet recovery was measured from randomization to platelet recovery (platelet count \>20,000/µL and \>100,000/µL)
Outcome Time Frame
Randomization to platelet recovery, for up to 60 days after the start of each treatment cycle
Outcome Measure
Time to Platelet Recovery
Outcome Description
Mortality (rate of death) of subjects by Day 30, measured from the first day of induction treatment to 30 days post-induction.
Outcome Time Frame
30 days (from first day of induction treatment to 30 days after)
Outcome Measure
Number of Subjects Who Died by Day 30
Outcome Description
Mortality (rate of death) of subjects by Day 60, measured from the first day of induction treatment to 60 days post-induction.
Outcome Time Frame
60 days (from the first day of induction treatment to 60 days after)
Outcome Measure
Number of Subjects Who Died by Day 60.
Outcome Description
Mortality (rate of death) of subjects at Day 90, measured from the first day of induction treatment to 90 days post-induction.
Outcome Time Frame
90 days (from the first day of induction treatment to 90 days after)
Outcome Measure
Number of Subjects Who Died by Day 90
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
60
Investigators
Investigator Type
Principal Investigator
Investigator Name
Ioannis Mantzaris
Investigator Email
IMANTZAR@montefiore.org
Investigator Phone
Categories Mesh Debug
Blood & Bone Marrow Cancers --- LEUKEMIA, MYELOID, ACUTE
Blood & Bone Marrow Cancers --- LEUKEMIA, MYELOID
Cancer --- LEUKEMIA
Blood & Bone Marrow Cancers --- LEUKEMIA
Cancer --- NEOPLASMS
Blood Disorders --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- HEMATOLOGIC DISEASES
MeSH Terms
LEUKEMIA, MYELOID, ACUTE
LEUKEMIA, MYELOID
LEUKEMIA
NEOPLASMS BY HISTOLOGIC TYPE
NEOPLASMS
HEMATOLOGIC DISEASES
HEMIC AND LYMPHATIC DISEASES
N-DESULFATED,2-O,3-O-DESULFATED HEPARIN
IDARUBICIN
CYTARABINE
DAUNORUBICIN
ANTHRACYCLINES
NAPHTHACENES
POLYCYCLIC AROMATIC HYDROCARBONS
HYDROCARBONS, AROMATIC
HYDROCARBONS, CYCLIC
HYDROCARBONS
ORGANIC CHEMICALS
POLYCYCLIC COMPOUNDS
AMINOGLYCOSIDES
GLYCOSIDES
CARBOHYDRATES
CYTIDINE
PYRIMIDINE NUCLEOSIDES
PYRIMIDINES
HETEROCYCLIC COMPOUNDS, 1-RING
HETEROCYCLIC COMPOUNDS
ARABINONUCLEOSIDES
NUCLEOSIDES
NUCLEIC ACIDS, NUCLEOTIDES, AND NUCLEOSIDES