Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

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

Fibrinolytic Agents

Anticoagulants

All Drugs and Chemicals

Antineoplastic Agents

Heparin

Daunorubicin

Calcium heparin

Idarubicin

Treatment with standard intensive induction, reinduction, or consolidation chemotherapy and dociparstat 4 mg/kg intravenous (IV) bolus on Day 1, administered 30 minutes after completion of the first dose of idarubicin or daunorubicin, followed by dociparstat 0.25 mg/kg/hr via continuous IV infusion 24 hours daily for 5 or 7 days.

Treatment with standard intensive induction, reinduction, or consolidation chemotherapy and placebo intravenous (IV) bolus on Day 1, administered 30 minutes after completion of the first dose of idarubicin or daunorubicin, followed by placebo via continuous IV infusion 24 hours daily for 5 or 7 days.

Dociparstat is a glycosaminoglycan derived from porcine heparin.

Dociparstat

Control

Phase 3 study to evaluate the efficacy and safety of dociparstat sodium in adults with newly diagnosed untreated acute myeloid leukemia (AML) with adverse or intermediate genetic risk.

A Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of dociparstat sodium in combination with standard intensive induction and consolidation chemotherapy for the treatment of newly-diagnosed acute myeloid leukemia (AML) patients.

Dociparstat in Combination With Standard Chemotherapy for the Treatment of Acute Myeloid Leukemia

A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Dociparstat Sodium in Combination With Standard Chemotherapy for the Treatment of Newly Diagnosed Acute Myeloid Leukemia

Overall survival was defined for all study participants through 5 years after randomization.

Overall survival was to be measured from the date of randomization to the date of death from any cause. Participants not known to have died at last follow-up contact were to be censored on the date they were last known to be alive.

Due to early termination, subjects did not complete long term follow-up and efficacy (including overall survival outcome) was not analyzed.

Chimerix

Adverse events were collected in all subjects from the time of the first dose through 42 days after the start of the last cycle with study intervention (i.e., dociparstat or placebo administered during initial induction, reinduction, or consolidation therapy).

Treatment with standard intensive induction, reinduction, or consolidation chemotherapy and Dociparstat 4 mg/kg IV bolus on Day 1, administered 30 minutes after completion of the first dose of idarubicin or daunorubicin, followed by Dociparstat 0.25 mg/kg/hr via continuous IV infusion 24 hours daily for 5 or 7 days.

Dociparstat sodium: Dociparstat is a glycosaminoglycan derived from porcine heparin.

Dociparstat Sodium (DSTAT)

Treatment with standard intensive induction, reinduction, or consolidation chemotherapy and Placebo IV bolus on Day 1, administered 30 minutes after completion of the first dose of idarubicin or daunorubicin, followed by Placebo via continuous IV infusion 24 hours daily for 5 or 7 days.

Placebo: 0.9% Normal Saline

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Due to low subject accrual, study enrollment was prematurely terminated on 16 May 2021. Therefore, formal statistical analyses were not performed, and no conclusions can be drawn about dociparstat with regards to efficacy.

Chief Medical Officer

Due to the early termination of the study, efficacy (overall survival) was not formally analyzed.

Overall Survival

Overall Study

Digestive System Diseases

Gland and Hormone Related Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Antimetabolites

During the Run-In Period, patients will receive gemcitabine + nab-paclitaxel + dociparstat to assess the compatibility of the combination.

• Nab-paclitaxel + gemcitabine + dociparstat:

* Nab-paclitaxel 125 mg/m2 will be administered intravenously (IV) over 30 minutes followed by the administration of gemcitabine IV infusion at 1000 mg/m2 over 30 minutes. Nab paclitaxel + gemcitabine will be administered weekly for 3 weeks followed by 1 week of rest (28-day cycle).
* Dociparstat IV bolus at 4 mg/kg will be administered in 5 minutes immediately following the completion of gemcitabine administration.
* Dociparstat 48-hour IV continuous infusion at 0.375 mg/kg/hr will be administered immediately following the dociparstat IV bolus administration.

Patients randomized to Arm A will receive gemcitabine + nab-paclitaxel + dociparstat.

• Nab-paclitaxel + gemcitabine + dociparstat:

* Nab-paclitaxel 125 mg/m2 will be administered IV over 30 minutes followed by the administration of gemcitabine IV infusion at 1000 mg/m2 over 30 minutes. Nab paclitaxel + gemcitabine will be administered weekly for 3 weeks followed by 1 week of rest (28-day cycle).
* Dociparstat IV bolus at 4 mg/kg will be administered in 5 minutes immediately following the completion of gemcitabine administration.
* Dociparstat 48-hour IV continuous infusion at 0.375 mg/kg/hr will be administered immediately following the dociparstat IV bolus administration.

Patients randomized to Arm B will receive gemcitabine + nab-paclitaxel. • Nab-paclitaxel + gemcitabine:

o Nab-paclitaxel 125 mg/m2 will be administered IV over 30 minutes followed by the administration of gemcitabine IV infusion at 1000 mg/m2 over 30 minutes. Nab paclitaxel + gemcitabine will be administered weekly for 3 weeks followed by 1 week of rest (28-day cycle).

Nab-paclitaxel 125 mg/m2 will be administered IV over 30 minutes. Nab-paclitaxel will be administered weekly for 3 weeks followed by 1 week of rest (28-day cycle).

Nab paclitaxel

Following the completion of nab-paclitaxel administration, gemcitabine IV infusion at 1000 mg/m2 will be administered over 30 minutes. Gemcitabine will be administered weekly for 3 weeks followed by 1 week of rest (28-cycle).

Following the completion of gemcitabine administration, dociparstat IV bolus at 4 mg/kg will be administered in 5 minutes immediately after completion of gemcitabine administration. Immediately following the dociparstat IV bolus administration, dociparstat 48-hour IV continuous infusion at 0.375 mg/kg/hr will be administered.

Mitesh J Borad, MD

Stephen Marcus, MD

This randomized, Phase 2, open label study aims to assess the efficacy and safety of gemcitabine + nab paclitaxel with or without dociparstat (ODSH) as first line treatment of metastatic pancreatic cancer. This study consists of 2 periods: a Run-in Period and a Randomized Period.

Dociparstat (ODSH) has demonstrated in vitro and in vivo inhibitory activity on mechanisms that are believed to play important roles in pancreatic cancer invasion, metastasis, and resistance to chemotherapy and radiation. Pancreatic cancer appears to have a dependence on autophagy, a regulated catabolic pathway to degrade and recycle cellular organelles and macromolecules. Autophagy appears to be largely driven by the binding of high mobility group box-1 protein (HMGB1) to the receptor for advanced glycation end-products (RAGE), which is strongly inhibited by dociparstat. Autophagy appears to not only assist pancreatic cancer cells to survive in a hypoxic, relatively avascular environment, but also appears to play an important role in chemotherapy resistance. Other important biological activities promoting pancreatic cancer invasion and metastasis affected by dociparstat include the inhibition of heparanase and the binding of tumor cells to endothelium and platelets mediated by the selectins. It is believed that these biological activities such as the inhibition of RAGE, heparanase, and selectin-mediated metastasis, can be inhibited by dociparstat at dose levels that can safely be administered without clinically significant anticoagulation.

The standard of care of pancreatic cancer is evolving. It appears that 2 combination regimens, the "FOLFIRINOX" regimen (a combination of 5-fluorouracil, leucovorin, irinotecan and oxaliplatin) and the combination of gemcitabine + nab-paclitaxel, could have more activity than the previous standard treatment of gemcitabine alone.

Patients with advanced metastatic pancreatic cancer who have not received chemotherapy, surgical or radiation treatments and have a good performance status are eligible to participate in this study. This study consists of 2 periods: a Run-in Period and a Randomized Period. In total, 10 patients are planned to be enrolled in a Run-in Period to receive gemcitabine + nab-paclitaxel + dociparstat. Pharmacokinetic sampling and safety assessments are to be conducted to decide on the continuation to the Randomized Period of the study where 50 patients are planned to be randomized at a 1:1 ratio to either of the 2 study arms:

* Arm A: Patients will receive gemcitabine + nab-paclitaxel + dociparstat
* Arm B: Patients will receive gemcitabine + nab-paclitaxel

The primary endpoint of this study is mean progression free survival. The secondary endpoints of this study are to consist of tumor response by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, overall survival at the end of the study, and changes from baseline for carbohydrate antigen (CA) 19-9 marker, weight, and plasma albumin.

Phase 2 Study to Assess the Efficacy & Safety of Gemcitabine + Nab Paclitaxel With or Without Dociparstat in Metastatic Pancreatic Cancer Patients

A Randomized Phase II Open Label Study to Assess the Efficacy & Safety of Gemcitabine + Abraxane® With or Without ODSH (2-0, 3-0 Desulfated Heparin) as First Line Treatment of Metastatic Pancreatic Cancer

The primary objective of this study is to evaluate progression-free survival (PFS) according to Response Evaluation Criteria In Solid Tumors (RECIST) Guidelines Version 1.1. This will be assessed from Baseline to disease progression or death (whichever occurred first), for up to 9 months.

A secondary objective of this study is to evaluate overall survival at the End of the Study.

Translational Drug Development

Anti-Infective Agents

Cytarabine

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.

Dociparstat sodium

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.

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.

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 in Combination With Standard Chemotherapy for the Treatment of Acute Myeloid Leukemia	NCT04571645	Acute Myeloid L...	Dociparstat Control	18 Years -	Chimerix
Phase 2 Study to Assess the Efficacy & Safety of Gemcitabine + Nab Paclitaxel With or Without Dociparstat in Metastatic Pancreatic Cancer Patients	NCT01461915	Metastatic Panc...	Nab paclitaxel Gemcitabine Dociparstat	18 Years - 75 Years	Chimerix
A Pilot Study of Dociparstat Sodium (ODSH) in Acute Myeloid Leukemia	NCT02056782	Acute Myeloid L...	Dociparstat sod...	18 Years - 80 Years	Chimerix
Phase 2 Study to Assess the Efficacy & Safety of Gemcitabine + Nab Paclitaxel With or Without Dociparstat in Metastatic Pancreatic Cancer Patients	NCT01461915	Metastatic Panc...	Nab paclitaxel Gemcitabine Dociparstat	18 Years - 75 Years	Chimerix

Spots Global Cancer Trial Database for dociparstat

Every month we try and update this database with for dociparstat cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for dociparstat

Every month we try and update this database with for dociparstat cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for dociparstat cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.