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

Acute Myeloid Leukemia Clinical Trial

Official title:

A Randomized, Phase II Study of CX-01 Combined With Standard Induction Therapy for Newly Diagnosed Acute Myeloid Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02873338
• Other study ID #: CNTX-CX-01-2015-AML-1
• Status: Completed
• Phase: Phase 2
• Start date: August 2016
• Est. completion date: June 2019

Study information

• Verified date: August 2023
• Source: Chimerix
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: June 2019
• Est. primary completion date: June 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Dociparstat sodium
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.
• Idarubicin
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.
• Cytarabine
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.

Locations

Country	Name	City	State
United States	New Mexico Cancer Care Alliance	Albuquerque	New Mexico
United States	Montefiore Medical Center	Bronx	New York
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Cincinnati	Cincinnati	Ohio
United States	Baylor Research Institute/Baylor Sammons Cancer Center/Baylor University Medical Center	Dallas	Texas
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Franciscan St. Francis Health	Indianapolis	Indiana
United States	University of California, San Diego, Moores Cancer Center	La Jolla	California
United States	Northwell Health, Monter Cancer Center	Lake Success	New York
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Allina Health - Virginia Piper Cancer Institute	Minneapolis	Minnesota
United States	Tennessee Oncology/Sarah Cannon Research Institute	Nashville	Tennessee
United States	Tulane University/Tulane Cancer Center	New Orleans	Louisiana
United States	Oregon Health & Science University Knight Cancer Institute	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Washington University School of Medicine in St. Louis	Saint Louis	Missouri
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	LDS Hospital	Salt Lake City	Utah
United States	Methodist Healthcare System of San Antonio	San Antonio	Texas
United States	June E. Nylen Cancer Center	Sioux City	Iowa
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	George Washington University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Chimerix

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	During induction and re-induction phases of treatment (up to 60 days after the start of each treatment cycle)
Secondary	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.	Randomization up to 30 months
Secondary	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.	Randomization until disease relapse or patient death from any cause, whichever occurs first, assessed up to 30 months
Secondary	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.	Randomization to end of study (18 months)
Secondary	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.	Up to 60 days after the start of each treatment cycle
Secondary	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)	Randomization to end of study (18 months)
Secondary	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.	Randomization to ANC recovery, for up to 60 days after the start of each treatment cycle
Secondary	Time to Platelet Recovery	Platelet recovery was measured from randomization to platelet recovery (platelet count >20,000/µL and >100,000/µL)	Randomization to platelet recovery, for up to 60 days after the start of each treatment cycle
Secondary	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.	30 days (from first day of induction treatment to 30 days after)
Secondary	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.	60 days (from the first day of induction treatment to 60 days after)
Secondary	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.	90 days (from the first day of induction treatment to 90 days after)