Evaluation of Dalteparin for Long-term (One Year) Treatment of Blood Clots in Subjects With Cancer

FRAG-A001-401: Dalteparin Sodium Injection (Fragmin), Multicenter, Open-Label, Single-arm, Long Term (52 Weeks) Study for Understanding the Safety and Efficacy in Subjects With Malignancies and Symptomatic Venous Thromboembolism

The purpose of this study is to determine the long term tolerability and safety of dalteparin in subjects with cancer.

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Drug: dalteparin

• Study Type: Interventional
• Enrollment (Actual): 338
• Phase: Phase 4

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria
    • LKH Graz Univrsitatstklinik fur Innere Medizin
  • Innsbruck, Austria
    • Medizinische Universitat Innsbruck Studienambulanz Hamatologie
  • Linz, Austria
    • KH d. Elizabethinen Linz GmbH Servicestelle fur klin. Studien und Universitare Angelegenheiten
  • Linz, Austria
    • KH der Barmherzigen Schwestern
  • St. Poelten, Austria
    • Dialysestation Landesklinkum St.Poelten
  • Vienna, Austria
    • Medizinische Universitat Wien
• Canada
  • Alberta
    • Edmonton, Alberta, Canada
      • University of Alberta
  • British Columbia
    • Vancouver, British Columbia, Canada
      • Vancouver General Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada
      • Queen Elizabeth II Health Sciences Centre
  • Ontario
    • London, Ontario, Canada
      • London Health Sciences Centre
    • Ottawa, Ontario, Canada
      • Ottawa Health Research Institute
    • Toronto, Ontario, Canada
      • University Health Network-Toronto General Hospital
  • Quebec
    • Montreal, Quebec, Canada
      • Sir Mortimer B. Davis Jewish General Hospital
    • Montreal, Quebec, Canada
      • Maisonneuve-Rosemont Hospital
• Netherlands
  • Apeldoorn, Netherlands
    • Gelre Ziekenhuizen-Locatie Apeldoorn
  • Sittard-Geleen, Netherlands
    • Orbis Medisch Centrum, Sittard-Geleen
• Spain
  • Barcelona, Spain
    • Hospital clinic i Provincial de Agencia de Ensayos Clinicos
  • Caragena (Murcia), Spain
    • Hospital General Santa Maria del Rosell
  • El Palmar (Murcia), Spain
    • Hospital Virgen de la Arrixaca
  • Girona, Spain
    • Hospital Universitari Dr Josep Trueta
  • Pamplona, Spain
    • Clínica Universitaria de Navarra
• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • Arizona Cancer Center
  • California
    • Pleasant Hill, California, United States, 94523
      • Bay Area Cancer Research Group
    • Torrance, California, United States, 90509
      • Harbor-UCLA Medical Center
  • Connecticut
    • Farmington, Connecticut, United States, 6030
      • University of CT Health Center
    • Norwich, Connecticut, United States, 6360
      • Eastern Connecticut Hematology and Oncology Associates
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Hospital-Lombardi Cancer Ctr
  • Florida
    • Daytona Beach, Florida, United States, 32114
      • Halifax Health
  • Georgia
    • Decatur, Georgia, United States, 30030
      • Atlanta Institute for Medical Research
  • Illinois
    • Skokie, Illinois, United States, 60076
      • Orchard Healthcare Research Inc.
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • James Graham Brown Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 2115
      • Bringham and Women's Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital K-15
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
    • Stony Brook, New York, United States, 11794
      • Stony Brook University, Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • MidDakota Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19106
      • Pennsylvania Oncology Hematology Associates
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Vermont
    • Burlington, Vermont, United States, 5401
      • Vermont Cancer Center at Fletcher Allen Health Care
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male and female subjects, age greater than or equal to 18 years of age.
2. Females should be either of non-childbearing potential as a result of surgery, radiation therapy, menopause (one year post onset), or of childbearing potential and willing to adhere to an acceptable method of pregnancy prevention.
3. Subjects must be newly diagnosed, symptomatic proximal deep-vein thrombosis of the lower extremity, pulmonary embolism, or both.
4. Subjects must have active malignancy defined as a diagnosis of cancer (excluding basal cell or squamous cell carcinoma of the skin) within six months before enrollment, having received any treatment for cancer within the previous six months, or having documented recurrent or metastatic cancer.
5. Prior to enrollment, subjects must not have received therapeutic doses of anticoagulant therapy (including low molecular weight heparin [LMWH]) for >48 hours (or >4 doses within 48 hours).
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
7. Subjects must have a life expectancy of >6 months.
8. Subjects must have a platelet count of >75,000 mm^3.
9. The subject must not be on any oral anticoagulant therapy for concomitant diseases.
10. Subjects must have no active or serious bleeding episodes within two weeks prior to study entry.
11. Subjects must be able to comply with scheduled follow-ups.

Exclusion Criteria:

1. Subjects who have a high risk of serious bleeding (e.g., recent neurosurgery within 30 days, history of intracranial hemorrhage, acute gastroduodenal ulcer, etc.).
2. Subjects who are on hemodialysis.
3. Subjects who have a prior placement of a Greenfield filter or other device to prevent embolization of deep vein thromboses.
4. Subjects with a known contraindication to the use of heparin (e.g., heparin-induced thrombocytopenia).
5. Subjects with a known hypersensitivity to heparin, dalteparin sodium, other LMWHs or pork products.
6. Subjects who are currently participating in another clinical trial involving anticoagulation therapy (with the exception of acetylsalicylic acid (ASA) in the 30 days prior to study entry, or who are actively using any investigational drugs/treatments 30 days prior to study entry involving anticoagulation therapy (with the exception of ASA , t.i.d).
7. Subject is pregnant or breast feeding.
8. Subjects with uncontrolled hypertension characterized by a sustained systolic pressure >170 mmHg and/or diastolic pressure >100 mmHg.
9. Subjects with a serious concomitant systemic disorder (for example, active infection including HIV or cardiac disease) that in the opinion of the investigator, would compromise the subject's ability to complete the study.
10. Any condition that makes the subject unsuitable in the opinion of the investigator.
11. Subjects with leukemia or myeloproliferative syndrome.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: dalteparin; Daily subcutaneous injection 200IU/kg dalteparin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Major Bleeding Events Adjudicated by Central Adjudication Committee	A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of greater than or equal to (>=) 2 gram per deciliter (g/dL), 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. In this outcome measure, number of participants with major bleeding events (adjudicated by Central Adjudication Committee) were reported.	Month 2 up to Month 6
Number of Participants With Major Bleeding Events Adjudicated by Central Adjudication Committee	A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of >=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. In this outcome measure, number of participants with major bleeding events (adjudicated by Central Adjudication Committee) were reported.	Month 7 up to Month 12
Number of Participants With New or Recurrent Venous Thromboembolism (VTE) Adjudicated by Central Adjudication Committee	VTEs included both deep vein thrombosis (DVT) and pulmonary embolism (PE). DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes pulmonary embolism (PE). When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. In this outcome measure, number of participants with new or recurrent VTE (adjudicated by Central Adjudication Committee) were reported.	Month 7 up to Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Investigator Identified Major Bleeding Events	A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of >=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. In this outcome measure, number of participants with major bleeding events (identified by investigator) were reported.	Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12
Number of Participants With Any Bleeding Event (Major or Minor) Adjudicated by Central Adjudication Committee	A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of >=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. A bleeding event was considered as minor if it was clinically overt but not meeting the criteria for major bleeding. In this outcome measure, number of participants with any (major or minor) bleeding events (adjudicated by Central Adjudication Committee) were reported.	Month 1 up to Month 6, Month 7 up to Month 12, Month 1 up to Month 12, Month 2 up to Month 6, and Month 2 up to Month 12
Number of Participants With Fatal Bleeding Events	Fatal bleeding events refers to those bleeding events which leads to death of participant. In this outcome measure, number of participants with fatal bleeding events were reported.	Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12
Time to First Occurrence of Major Bleeding Event Adjudicated by Central Adjudication Committee	Time to first occurrence of major bleeding event was defined as the time interval (in days) between the date of first study treatment and the date of documentation of first major bleeding event. A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of >=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death.	Month 1 up to Month 12
Time to First Occurrence of Any Bleeding Event (Major or Minor) Adjudicated by Central Adjudication Committee	Time to first occurrence of any bleeding event was defined as the time interval (in days) between the date of first study treatment and the date of documentation of first bleeding event (major or minor). A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of >=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. A bleeding event was considered as minor if it was clinically overt but not meeting the criteria for major bleeding.	Month 1 up to Month 12
Number of Participants With Investigator Identified New or Recurrent Venous Thromboembolism (VTEs)	VTEs included both DVT and PE. DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes PE. When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. In this outcome measure, number of participants with new or recurrent VTE (identified by investigator) were reported.	Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12
Number of Participants With New or Recurrent Venous Thromboembolism (VTE) or Central Venous Thrombosis (CVT) Adjudicated by Central Adjudication Committee	VTEs included both DVT and PE. DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes PE. When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. CVT is blood clot of the venous channels in the brain. CVT was diagnosed by contrast venography or ultrasonography. In this outcome measure, number of participants with new or recurrent VTE or CVT (adjudicated by Central Adjudication Committee) were reported.	Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12
Number of Participants With Investigator Identified New or Recurrent Venous Thromboembolism (VTE) or Central Venous Thrombosis (CVT)	VTEs included both DVT and PE. DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes PE. When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. CVT is blood clot of the venous channels in the brain. CVT was diagnosed by contrast venography or ultrasonography. In this outcome measure, number of participants with new or recurrent VTE or CVT (identified by investigator) were reported.	Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12
Time to First Occurrence of New or Recurrent Venous Thromboembolism (VTE) Adjudicated by Central Adjudication Committee	Time to first occurrence of new or recurrent VTE was defined as the time interval (in days) between the date of first study treatment and the date of documentation of first VTE. VTEs included both DVT and PE. DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes PE. When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram.	Month 1 up to Month 12
Time to First Occurrence of New or Recurrent VTE or CVT Adjudicated by Central Adjudication Committee	Time to first occurrence of new or recurrent VTE or CVT was defined as the time interval (in days) between the date of first study treatment and the date of documentation of first VTE or CVT. VTEs included both deep vein thrombosis (DVT) and pulmonary embolism (PE) .DVT is a blood clot in the deep veins of the leg. If a DVT clot that breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes pulmonary embolism (PE). When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan, contrast venography or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. CVT is blood clot of the venous channels in the brain. CVT was diagnosed by contrast venography or ultrasonography.	Month 1 up to Month 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Week 52 that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs.	Baseline (Day 1) up to Week 52
Number of Participants With Clinically Significant Laboratory Abnormalities	Criteria for abnormality: Hemoglobin greater than or equal to(>=)130*lower limit of normal(LLN); less than or equal to(<=)170*upper limit of normal(ULN), hematocrit >=0.39*LLN;<=0.51*ULN, red blood cell >=4.5*LLN;<=5.9*ULN, platelet>=150*LLN;<= 450*ULN, white blood cells >=4*LLN;<=11*ULN; lymphocytes>=0.09;<=0.44, neutrophils=>0.16*LLN;<=0.7*ULN, eosinophils<=0.04*ULN, basophils<=0.02*ULN, monocytes>0.08*ULN; bilirubin >=5.1*LLN;<=22.2*ULN, aspartate aminotransferase >=13*LLN;<=36*ULN, alanine aminotransferase>=11*LLN;<=54*ULN, alkaline phosphatase>=31*LLN ;<=104 *ULN, total protein>=60*LLN; <=76*ULN, albumin=>35*LLN;<=50*ULN, glucose>=3.77 ;<=6.05;blood urea nitrogen>=1.785*LLN;<=7.5*ULN, creatinine>=70.7*LLN;<=114.9*ULN, creatinine kinase>=30*LLN ;<=280*ULN, lactate dehydrogenase>=85*LLN;<=180*ULN, sodium>=137*LLN ;<=144*ULN, potassium >=3.5*LLN;<=5*ULN, chloride>=102*LLN;<=111*ULN, calcium>=2.22*LLN ;<=2.57*ULN, phosphorus=>0.81 ;<=1.45); nitrogen cholesterol>=1.78*LLN ;<=7.49*ULN.	Baseline (Day 1) up to Week 52
Number of Participants With Abnormal Physical Examinations Findings	Physical examinations included head, ears, nose, throat (ENT), neck, heart, chest, lungs, abdomen, extremities, neurological systems, skin, general appearance and others (thigh, abdomen unobtrusive scar, breast, cardio-vascular, constitutional, face, genitalia, genitourinary, gastrointestinal, hematologic, left ankle unobtrusive scar, lymph nodes, lymphatic, malaise/fatigue, mouth, musculoskeletal, musculoskeletal, peripherally inserted central catheters line site left arm, psychiatric, skeletal, urinary, weight, activity level, bladder irritation, dyspnea and eastern cooperative oncology group performance status [used to assess how the disease affects the daily living abilities of the participant. It ranges on the scale from 0-5 (0= normal activity; 1= symptoms but ambulatory; 2= in bed for less than (<) 50 percent (%) of the time; 3= in bed for greater than (>) 50% of the time; 4= 100% bedridden; 5= dead]). Abnormality in physical examinations was based on investigator's discretion.	Baseline (Day 1), Week 1, 4, 8, 12, 24, 36, 48, 52
Other Pre-specified: Number of Participants With Clinically Significant Electrocardiogram Findings	Clinically significant ECG findings included: corrected QT (QTc) > 450 ms, QTc >500 ms, change in QTc between 30 and 60 ms, change in QTc greater than or equal to 60 ms.	Baseline up to Week 52
Change From Baseline in Creatinine Clearance at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 in Severely Renal Impaired Participants	Creatinine clearance is an indicator of renal function. Creatinine clearance is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Normal values for healthy, young males are in the range of 100-135 milliliters per minute (mL/min) and for females, 90-125 mL/min. Creatinine clearance decreases with age.	Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Gary Palmer, MD, Medical Affairs, Eisai, Inc; Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: July 16, 2009
• First Submitted That Met QC Criteria: July 20, 2009
• First Posted (Estimated): July 21, 2009

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin
• Other Study ID Numbers: FRAG-A001-401; A6301095 (Other Identifier: Alias Study Number)