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

Chimerix

Status and phase: Completed; Phase 2

Conditions: Acute Myeloid Leukemia

Treatments: Drug: Idarubicin; Drug: Cytarabine; Drug: Dociparstat sodium

Study type: Interventional

Funder types: Industry

Identifiers

NCT02873338

CNTX-CX-01-2015-AML-1

Details and patient eligibility

About

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.

Full 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.

Enrollment: 75 patients

Sex: All

Ages: 60+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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75 participants in 3 patient groups

Control (idarubicin+cytarabine)

Active Comparator group

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)

Treatment:

Drug: Idarubicin

Drug: Cytarabine

Dociparstat 0.125 mg/kg

Experimental group

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)

Treatment:

Drug: Dociparstat sodium

Drug: Idarubicin

Drug: Cytarabine

Dociparstat 0.25 mg/kg

Experimental group

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)

Treatment:

Drug: Dociparstat sodium

Drug: Idarubicin

Drug: Cytarabine