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Acute Myeloid LeukemiaPhase 1PGX-AMLNCT02056782

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

A Phase 1 study testing Dociparstat sodium in people with Acute Myeloid Leukemia, run by Jazz Pharmaceuticals.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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). Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Dociparstat sodium
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
No sites listed yet
Study dates
Dec 2013to Jun 2015
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • All patients had to meet the following criteria to be eligible for this study:
  • Had newly diagnosed, previously untreated acute myeloid leukemia (AML). Acute promyelocytic leukemia and acute megakaryoblastic leukemia subtypes were excluded
  • Had no prior chemotherapy for AML; however, prior hydroxyurea to control white blood cell count was allowed
  • Was aged 18 years or older.
  • Had an Eastern Cooperative Oncology Group (ECOG) Performance status of 0-2.
  • Had a cardiac ejection fraction ≥ 50% (echocardiography or Multi-Gated Acquisition Scan [MUGA]).
  • Had adequate hepatic and renal function (aspartate aminotransferase [AST], alanine aminotransferase [ALT], bilirubin and creatinine < 2.5 x upper normal limit).
  • Was able to provide informed consent and signed an approved consent form that conformed to federal and institutional guidelines.

Who cannot join

  • Patients who met any of the following criteria were not eligible to be enrolled in this study:
  • Had acute promyelocytic leukemia.
  • Had acute megakaryoblastic leukemia.
  • Had central nervous system (CNS) leukemia
  • Had the presence of uncontrolled bleeding.
  • Had the presence of significant active infection that was uncontrolled, as judged by the Investigator.
Show all 21Show fewer
  • Had a history of severe congestive heart failure or other cardiac disease that contraindicated the use of anthracyclines, including idarubicin.
  • Had pre-existing liver disease.
  • Had renal insufficiency, which, in the opinion of the Investigator, might have adversely affected the schedule and dose of therapy with cytarabine, as well as the management of tumor lysis syndrome. Patients with creatinine levels ≥2 mg/dL were not eligible.
  • Had use of recreational drugs or history of drug addiction, within the prior 6 months.
  • Had known history of positive hepatitis B surface antigens or hepatitis C virus (HCV) antibodies.
  • Had known history of positive test for human immunodeficiency virus (HIV) antibodies
  • Had psychiatric or neurologic conditions that could have compromised patient safety or compliance, or interfered with the ability to give proper informed consent.
  • Had history of other active malignant disease within 5 years, other than cured basal cell carcinoma of the skin, cured in situ carcinoma of the cervix, or localized prostate cancer that had received definitive therapy. Such prostate cancer patients who were receiving hormonal therapy were eligible.
  • Had the presence of disseminated intravascular coagulation, as confirmed by laboratory studies demonstrating evidence of both increased thrombin generation (decreased fibrinogen, prolonged prothrombin time [PT] and partial thromboplastin time [aPTT]), as well as increased fibrinolysis (elevated D-dimer level).
  • Had received any form of anticoagulant therapy.
  • Had the presence of a known bleeding disorder or coagulation abnormality.
  • Had received treatment with any other investigational agent within 7 days prior to study entry. All prior toxicities should have been resolved to no greater than Grade 1 (with the exception of alopecia).
  • Were pregnant or breast-feeding patients.
  • Were of childbearing potential and were not using adequate contraception.
  • Had any condition that required maintenance of platelet counts at 50,000/μL or higher.

About this study

Official title: 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

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).

Read the detailed description

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.

Being tested
Dociparstat sodium
Keywords
Acute Myeloid Leukemia, AML, ODSH, ODSH-AML, CX-01, dociparstat, dociparstat sodium, 2-O, 3-O desulfated heparin
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dociparstat sodiumDrug

    Also called dociparstat, ODSH, CX-01, 2-O, 3-O desulfated heparin

    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.
Study groups in NCT02056782
Study groupRoleWhat they receive
DociparstatExperimentalThe 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.
Receives: Drug: Dociparstat sodium

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    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.

    Measured: Day 1 to Day 35 (35 days)

Secondary outcomes (1)

  1. Number of Subjects Who Achieved a Morphologic Complete Remission

    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.

    Measured: Day 1 to Day 35 (35 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Feb 2014 (estimated)
  2. Study startDec 2013
  3. Primary completionFeb 2015
  4. Study completionJun 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02056782
Sponsor's protocol ID
PGX-ODSH-2013-AML-1
Acronym
PGX-AML
Status last verified
May 2022
First submitted
22 Jan 2014
Last updated
21 Feb 2023
Data monitoring committee
Yes
Individual data sharing
Undecided

Publications

  • Greer JP, Baer MR, Kinney MC. Acute Myelogenous Leukemia in Adults. In Wintrobe's Clinical Hematology. Lee GR et al ed. Williams and Wilkins, Baltimore, 2098-2142, 2004.

  • Stroncek DF, Rebulla P. Platelet transfusions. Lancet. 2007 Aug 4;370(9585):427-38. doi: 10.1016/S0140-6736(07)61198-2.

    PubMed 17679020

  • Kuter DJ. What is the potential for thrombopoietic agents in acute leukemia? Best Pract Res Clin Haematol. 2011 Dec;24(4):553-8. doi: 10.1016/j.beha.2011.09.002. Epub 2011 Nov 4.

    PubMed 22127320

  • Trafalis DT, Poulakidas E, Kapsimali V, Tsigris C, Papanicolaou X, Harhalakis N, Nikiforakis E, Mentzikof-Mitsouli C. Platelet production and related pathophysiology in acute myelogenous leukemia at first diagnosis: prognostic implications. Oncol Rep. 2008 Apr;19(4):1021-6.

    PubMed 18357391

  • Stasi R, Bosworth J, Rhodes E, Shannon MS, Willis F, Gordon-Smith EC. Thrombopoietic agents. Blood Rev. 2010 Jul-Sep;24(4-5):179-90. doi: 10.1016/j.blre.2010.04.002. Epub 2010 May 20.

    PubMed 20493600

  • Majka M, Janowska-Wieczorek A, Ratajczak J, Kowalska MA, Vilaire G, Pan ZK, Honczarenko M, Marquez LA, Poncz M, Ratajczak MZ. Stromal-derived factor 1 and thrombopoietin regulate distinct aspects of human megakaryopoiesis. Blood. 2000 Dec 15;96(13):4142-51.

    PubMed 11110685

  • Lambert MP, Rauova L, Bailey M, Sola-Visner MC, Kowalska MA, Poncz M. Platelet factor 4 is a negative autocrine in vivo regulator of megakaryopoiesis: clinical and therapeutic implications. Blood. 2007 Aug 15;110(4):1153-60. doi: 10.1182/blood-2007-01-067116. Epub 2007 May 10.

    PubMed 17495129

  • Lambert MP, Reznikov A, Grubbs A, Nguyen Y, Xiao L, Aplenc R, Rauova L, Poncz M. Platelet factor 4 platelet levels are inversely correlated with steady-state platelet counts and with platelet transfusion needs in pediatric leukemia patients. J Thromb Haemost. 2012 Jul;10(7):1442-6. doi: 10.1111/j.1538-7836.2012.04767.x. No abstract available.

    PubMed 22564375

  • Lambert MP, Xiao L, Nguyen Y, Kowalska MA, Poncz M. The role of platelet factor 4 in radiation-induced thrombocytopenia. Int J Radiat Oncol Biol Phys. 2011 Aug 1;80(5):1533-40. doi: 10.1016/j.ijrobp.2011.03.039.

    PubMed 21740995

  • Joglekar MV, Quintana Diez PM, Marcus S, Qi R, Espinasse B, Wiesner MR, Pempe E, Liu J, Monroe DM, Arepally GM. Disruption of PF4/H multimolecular complex formation with a minimally anticoagulant heparin (ODSH). Thromb Haemost. 2012 Apr;107(4):717-25. doi: 10.1160/TH11-11-0795. Epub 2012 Feb 8.

    PubMed 22318669

  • Lambert MP, Sharma SS, Xiao L, Marcus S et al. 2-O, 3-O-Desulfated Heparin (ODSH) Mitigates Chemotherapy-Induced Thrombocytopenia (CIT) by Blocking the Negative Paracrine Effect of Platelet Factor 4 (PF4) On Megakaryopoiesis. Proceedings of the 54th Annual Meeting of the American Society of Hematology. Abstract 386, 2012.

  • Yang L, Yu Y, Kang R, Yang M, Xie M, Wang Z, Tang D, Zhao M, Liu L, Zhang H, Cao L. Up-regulated autophagy by endogenous high mobility group box-1 promotes chemoresistance in leukemia cells. Leuk Lymphoma. 2012 Feb;53(2):315-22. doi: 10.3109/10428194.2011.616962. Epub 2011 Nov 15.

    PubMed 21864037

  • Kang R, Tang D, Schapiro NE, Livesey KM, Farkas A, Loughran P, Bierhaus A, Lotze MT, Zeh HJ. The receptor for advanced glycation end products (RAGE) sustains autophagy and limits apoptosis, promoting pancreatic tumor cell survival. Cell Death Differ. 2010 Apr;17(4):666-76. doi: 10.1038/cdd.2009.149. Epub 2009 Oct 16.

    PubMed 19834494

  • Rao NV, Argyle B, Xu X, Reynolds PR, Walenga JM, Prechel M, Prestwich GD, MacArthur RB, Walters BB, Hoidal JR, Kennedy TP. Low anticoagulant heparin targets multiple sites of inflammation, suppresses heparin-induced thrombocytopenia, and inhibits interaction of RAGE with its ligands. Am J Physiol Cell Physiol. 2010 Jul;299(1):C97-110. doi: 10.1152/ajpcell.00009.2010. Epub 2010 Apr 7.

    PubMed 20375277

  • Abe R, Shimizu T, Sugawara H, Watanabe H, Nakamura H, Choei H, Sasaki N, Yamagishi S, Takeuchi M, Shimizu H. Regulation of human melanoma growth and metastasis by AGE-AGE receptor interactions. J Invest Dermatol. 2004 Feb;122(2):461-7. doi: 10.1046/j.0022-202X.2004.22218.x.

    PubMed 15009731

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Dociparstat sodium in people with Acute Myeloid Leukemia, run by Jazz Pharmaceuticals.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time (Days) to Transfusion-independent Platelet Recovery (Platelet Counts Values ≥ 20,000/μL and ≥ 50,000/μL Without a Platelet Transfusion) (time frame: Day 1 to Day 35 (35 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02056782, which also lists 31 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2023.

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