Neoplasms

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Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Fibrinolytic Agents

Anticoagulants

Cytarabine

Heparin

Calcium heparin

Idarubicin

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

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)

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.

Dociparstat sodium

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.

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.

Stephen Marcus, MD

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.

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.

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

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

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.

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.

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.

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.

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.

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)

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.

Platelet recovery was measured from randomization to platelet recovery (platelet count \>20,000/µL and \>100,000/µL)

Mortality (rate of death) of subjects by Day 30, measured from the first day of induction treatment to 30 days post-induction.

Mortality (rate of death) of subjects by Day 60, measured from the first day of induction treatment to 60 days post-induction.

Mortality (rate of death) of subjects at Day 90, measured from the first day of induction treatment to 90 days post-induction.

Chimerix

Note that all-cause mortality was assessed for all randomized participants and adverse events were monitored for only participants who received at least 1 dose of study drug; 2 participants (1 in the control group and 1 in the 0.25 mg/kg dociparstat group) were randomized but did not receive study drug and were therefore not monitored for adverse events.

Control (Idarubicin+Cytarabine)

Dociparstat 0.125 mg/kg

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-hr 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

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Acute myeloid leukemia (AML) subtype

Time since acute myeloid leukemia (AML) diagnosis

Baseline blasts in bone marrow

Chief Medical Officer

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/h 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)

Number of Subjects Who Achieved Morphologic Complete Remission

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-hr 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-hr 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)

Note: In the Dociparstat 0.125 mg/kg group, fewer than half of the subjects achieved complete CR, and thus were assessed as having an event on Day 1.

Duration of Event-free Survival

This analysis only included subjects who achieved composite complete remission. The following number of subjects were censored in each treatment group:

* Control: 6/16 (37.5%) subjects
* Dociparstat 0.125 mg/kg: 4/9 (44.4%) subjects
* Dociparstat 0.25 mg/kg: 10/15 (66.7%) subjects

Time to Leukemia-free Survival

Number of Subjects Who Achieved Overall Survival

Number of Subjects Who Achieved Composite Complete Remission

This analysis only included subjects who had achieved morphologic complete remission.

The following number of subjects were censored in each treatment group for this analysis; however the full ranges include censored subjects:

* Control: 7/14 (50%) subjects
* Dociparstat 0.125 mg/kg: 6/8 (75.0%) subjects
* Dociparstat 0.25 mg/kg: 9/11 (81.8%) subjects

Duration of Morphologic Complete Remission

Recovery to >500/µL

Recovery to >1000/µL

The following number of subjects were censored in each treatment group for both analyses (neutrophil recovery to \>500/µL and \>1000/µL):

* Control: 6/26 (23.1%) subjects for both analyses (\>500/µL and \>1000/µL)
* Dociparstat 0.125 mg/kg: 9/25 (36.0%) subjects for both analyses (\>500/µL and \>1000/µL)
* Dociparstat 0.25 mg/kg: 7/24 (29.2%) subjects for \>500/µL and 11/24 (45.8%) subjects for \>1000/µL

Time to Recovery of Neutrophils

Recovery to >20,000µL

Recovery to >100,000µL

The following number of subjects were censored in each treatment group for each analysis (platelet recovery to \>20,000µL and \>100,000µL):

* Control: 5/26 (19.2%) subjects for \>20,000µL and 7/26 (26.9%) subjects for \>100,000µL
* Dociparstat 0.125 mg/kg: 5/25 (20%) subjects for \>20,000µL and 12/25 (48.0%) subjects for \>100,000µL
* Dociparstat 0.25 mg/kg: 8/24 (33.3%) subjects for \>20,000µL and 11/24 (45.8%) subjects for \>100,000µL

Time to Platelet Recovery

Number of Subjects Who Died by Day 30

Number of Subjects Who Died by Day 60.

Induction:

* Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-7)
* Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3)
* Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7)

Reinduction:

* Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion (Days 1-5)
* Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2)
* Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5)

Consolidation:

* Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.125 mg/kg/h continuous 24-hr IV infusion on (Days 1-5; total 120 hours)
* Cytarabine 1.0 g/m2 over 3 hrs, every 12 hrs (Days 1, 3, 5)

Number of Subjects Who Died by Day 90

Induction:

* Idarubicin 12 mg/m2/day by slow (10 to 30 minutes) intravenous (IV) injection/infusion daily (Days 1, 2, 3)
* Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7)

Reinduction:

* Idarubicin 12 mg/m2/day slow (10 to 30 minutes) IV injection/infusion daily (Days 1, 2)
* Cytarabine 100 mg/m2/day continuous 24-hour IV infusion (Days 1-5)

Consolidation:

• Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)

Induction:

* Dociparstat 4 mg/kg initial bolus 30 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-7)
* Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2, 3)
* Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-7)

Reinduction:

* Dociparstat 4 mg/kg initial bolus 20 minutes post-idarubicin dose (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5)
* Idarubicin 12 mg/m2/day slow IV injection/infusion daily (Days 1, 2)
* Cytarabine 100 mg/m2/day continuous 24-hr IV infusion (Days 1-5)

Consolidation:

* Dociparstat 4 mg/kg initial bolus 30 minutes post-3-hour cytarabine infusion (Day 1), followed by dociparstat 0.25 mg/kg/h continuous 24-hr IV infusion (Days 1-5; total 120 hours)
* Cytarabine 1.0 g/m2 over 3 hours, every 12 hours (Days 1, 3, 5)

Overall Study

The following induction regimen was administered:

* Cytarabine (100 mg/m2/day) via continuous intravenous (IV) infusion 24 hours daily for 7 days.
* Idarubicin (12 mg/m2/day) IV on Days 1, 2, and 3.
* Dociparstat (4 mg/kg) given over 5 minutes IV, immediately after the idarubicin dose on Day 1, followed by a continuous IV infusion (0.25 mg/kg/hr for 24 hours daily) for a total of 7 days.

This was an open-label pilot study that evaluated the safety and preliminary evidence of a therapeutic effect of dociparstat in conjunction with standard induction and consolidation therapy for acute myeloid leukemia (AML).

The primary objectives of this study were the following:

1. To evaluate the safety and tolerability of dociparstat in patients with acute myeloid leukemia (AML) receiving cytarabine and idarubicin induction or cytarabine consolidation chemotherapy.
2. To determine whether there is preliminary evidence of an effect of dociparstat on time to transfusion-independent platelet recovery in AML patients receiving cytarabine and idarubicin induction or cytarabine consolidation chemotherapy.

The secondary objectives of this study were the following:

1. To determine whether there is preliminary evidence of an effect of dociparstat on remission rate following cytarabine and idarubicin induction in AML patients.
2. To determine whether there is preliminary evidence of an effect of dociparstat on improving platelet nadir counts in AML patients receiving cytarabine and idarubicin induction or cytarabine consolidation chemotherapy.
3. To determine whether there is preliminary evidence of an effect of dociparstat on decreasing the number of platelet transfusions in AML patients receiving cytarabine and idarubicin induction or cytarabine consolidation chemotherapy.
4. To determine whether there is preliminary evidence of an effect of dociparstat on reducing overall side effects of chemotherapy in AML patients receiving cytarabine and idarubicin induction or cytarabine consolidation chemotherapy.

This study enrolled patients with newly diagnosed, previously untreated AML; subjects with acute promyelocytic leukemia and acute megakaryoblastic leukemia subtypes were excluded.

All patients were to receive standard induction chemotherapy with cytarabine 100 mg/m2/day by continuous intravenous (IV) infusion over 24 hours daily for 7 days (Days 1-7) plus idarubicin 12 mg/m2/day by IV injection daily for 3 days (Days 1-3). For consolidation, patients younger than 60 were to receive cytarabine at a dose of 3 grams/m2 over 3 hours, every 12 hours on days 1, 3, and 5.

Induction cycle: dociparstat 4 mg/kg IV bolus Day 1, 30 minutes after completion of administration of the first dose of idarubicin, then dociparstat 0.25 mg/kg/hour for 24 hours daily by continuous IV infusion Days 1-7.

Consolidation cycle: dociparstat mg/kg IV bolus Day 1 administered 30 minutes after completion of infusion of the first dose of cytarabine then dociparstat 0.25 mg/kg/hour for 24 hours daily by continuous IV infusion Days 1-5

In total, there were 7 days in the induction cycle and 5 days in the consolidation cycles.

A Pilot Study of Dociparstat Sodium (ODSH) in Acute Myeloid Leukemia

A Pilot Study to Evaluate the Safety and Preliminary Evidence of an Effect of ODSH (2 O, 3-O Desulfated Heparin) in Accelerating Platelet Recovery in Patients Receiving Induction or Consolidation Therapy for Acute Myeloid Leukemia

A primary endpoint of this study was evidence of an effect of dociparstat on transfusion independent platelet recovery time. The time (days) to transfusion-independent platelet recovery will be defined as the number of days from the first day of chemotherapy until the first of 5 consecutive days with platelet counts values ≥ 20,000/μL and ≥ 50,000/μL without a platelet transfusion.

A secondary endpoint of this study was to determine whether there was preliminary evidence of an effect of dociparstat on remission rate following cytarabine and idarubicin induction in acute myeloid leukemia (AML) patients, which included complete remission (CR) rate (with neutrophil and platelet count recovery) after the first induction cycle.

Morphologic CR was defined as absolute neutrophil count (ANC) \>1000/μL, platelet count \>100,000/μL, \<5% bone marrow blasts, no Auer rods, and no evidence of extramedullary disease.

Translational Drug Development

Subjects received the following dosing regimen:

* Cytarabine (100 mg/m2/day) via continuous intravenous (IV) infusion 24 hours daily for 7 days.
* Idarubicin (12 mg/m2/day) IV on Days 1, 2, and 3.
* Dociparstat (4 mg/kg) given over 5 minutes IV, immediately after the idarubicin dose on Day 1, followed by a continuous IV infusion (0.25 mg/kg/hr for 24 hours daily) for a total of 7 days.

Dociparstat

United States

Region of Enrollment

CBertrand

Platelet count of ≥20,000/µL

Platelet count of ≥50,000/µL

Count recovery was analyzed after induction on the 10 subjects who received a full induction cycle.

Time (Days) to Transfusion-independent Platelet Recovery (Platelet Counts Values ≥ 20,000/μL and ≥ 50,000/μL Without a Platelet Transfusion)

All randomized subjects were included in this analysis, including the 2 subjects who did not complete induction.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Dociparstat Sodium (CX-01) Combined With Standard Induction Therapy for Newly Diagnosed Acute Myeloid Leukemia	NCT02873338	Acute Myeloid L...	Dociparstat sod... Idarubicin Cytarabine	60 Years -	Chimerix
Dociparstat Sodium (CX-01) Combined With Standard Induction Therapy for Newly Diagnosed Acute Myeloid Leukemia	NCT02873338	Acute Myeloid L...	Dociparstat sod... Idarubicin Cytarabine	60 Years -	Chimerix
A Pilot Study of Dociparstat Sodium (ODSH) in Acute Myeloid Leukemia	NCT02056782	Acute Myeloid L...	Dociparstat sod...	18 Years - 80 Years	Chimerix

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