Fragmin for the Treatment of Acute VTE in Pediatric Cancer Patients

Study Overview
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Brief Summary
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Three month treatment of acute VTE with Fragmin in pediatric cancer patients

Detailed Description
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Primary study objectives include are to determine the pharmacodynamic (PD) profiles for treatment doses of dalteparin in pediatric subjects of different ages with cancer and venous thromboembolism (VTE), using anti-Xa (Xa) levels and a population PD analysis methodology, and to determine the median dose required to achieve therapeutic anti- Xa levels (0.5 to 1.0 International Units [IU]/mL) based on subject age and weight.

Official Title
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A THREE MONTH PROSPECTIVE OPEN LABEL STUDY OF THERAPY WITH FRAGMIN(REGISTERED) (DALTEPARIN SODIUM INJECTION) IN CHILDREN WITH VENOUS THROMBOEMBOLISM WITH OR WITHOUT MALIGNANCIES

Conditions
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Venous Thromboembolism

Intervention / Treatment
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* Drug: dalteparin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Exclusion Criteria: -

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Single Arm<br>Single arm open-label | Drug: dalteparin<br>* dalteparin subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Dose of Dalteparin Required to Achieve Prespecified Therapeutic Anti- Factor Xa Level | Prespecified therapeutic anti-factor Xa level was 0.5-1.0 international unit per milliliter (IU/mL). Cumulative data of Day 1 to 7 has been reported. | 4 hours post-dose at each Day 1 to 7 in dose adjustment phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved Prespecified Therapeutic Anti- Factor Xa Levels | Prespecified therapeutic anti-factor Xa level was 0.5-1.0 IU/mL. Percentage of participants who achieved the prespecified level during the dose adjustment phase were reported in this outcome measure. | Day 1 to 7 in dose adjustment phase | 
| Number of Participants With New or Progressive Symptomatic Venous Thromboembolism (VTE) | Symptomatic VTE defined as new or progressive signs and symptoms as judged by the investigator including but not limited to: objective swelling, pain or tenderness, pitting edema, erythema or cyanosis. Progression of VTE: Progression of clot burden in terms of severity of occlusion, or involvement of new venous segments at any time after the initial diagnosis. | Baseline up to 28 days after the last dose of study drug (up to Day 132) | 
| Time to First Occurrence of Symptomatic Recurrent Venous Thromboembolism (VTE) | It was defined as the time interval (in days) between date of first study treatment and 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 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 breaks, loose and travels in the blood, this is called VTE. VTE was confirmed by at least one radiographic test and was defined as any new or progressive VTE whose signs and symptoms (identified by the investigator) included: objective swelling or tenderness, pitting edema, erythema or cyanosis. | Baseline up to 28 days after the last dose of study drug (up to Day 132) | 
| Percentage of Participants With Clinical Response of Progression, Regression, Resolution and No Change in Venous Thromboembolism (VTE) | VTEs included both DVT and PE. DVT is a blood clot in the deep veins of the leg. PE is a blood clot in the lungs. Clinical response of progression was defined as progression of clot burden in terms of severity of occlusion, or involvement of new venous segments at any time after the initial diagnosis. Clinical response of regression: Regressed clot burden utilizing the same imaging modality as the screening visit. Clinical response of resolution: Thrombus resolution of the qualifying event measured by repeat imaging at the end of study (EOS) visit. | Baseline up to 28 days after the last dose of study drug (up to Day 132) | 
| Percentage of Participants With Major and Minor Bleeding Event | A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: fatal bleeding, bleeding accompanied by a decrease in hemoglobin of at least 2 grams per deciliter 24 hours, Overt bleeding deemed by the attending physician to necessitate permanent discontinuation of trial medication, Overt bleeding deemed by the attending physician to be unrelated to the participant's underlying condition and accompanied by blood product administration or bleeding occurred at a critical site (intraocular, intracranial, retroperitoneal). A bleeding event was considered as minor if it was clinically overt but not meeting the criteria for major or clinically relevant no major bleeding (bleeding resulting in any medical or surgical interventions but which did not meet the criteria for major bleeding). | Baseline up to 28 days after the last dose of study drug (up to Day 132) | 
| Number of Participants With Treatment Emergent Adverse Events (AEs) 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. 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 were events between first dose of study drug and up to 28 days after the last dose of study drug (up to Day 132) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs. | Baseline up to 28 days after the last dose of study drug (up to Day 132) | 
| Number of Participants With Laboratory Abnormalities | Criteria:hematology:hemoglobin, hematocrit, erythrocytes less than(<)0.8*lower limit of normal(LLN), platelets <0.5*LLN >1.75*upper limit of normal (ULN),leukocytes <0.6* LLN >1.5* ULN, lymphocytes, lymphocytes/Leukocytes, neutrophils, neutrophils/leukocytes <0.8* LLN >1.2* ULN, basophils, basophils/leukocytes, eosinophils, eosinophils/leukocytes monocytes monocytes/leukocytes >1.2*ULN, activated partial thromboplastin time, prothrombin time, prothrombin international normalized ratio >1.1* ULN. Clinical chemistry: bilirubin >1.5*ULN, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase >3.0*ULN, protein, albumin <0.8* LLN >1.2* ULN, blood urea nitrogen, creatinine >1.3* ULN, sodium <0.95*LLN >1.05*ULN, potassium, chloride, calcium, magnesium <0.9* LLN >1.1* ULN, phosphate <0.8* LLN >1.2* ULN, glucose <0.6*LLN >1.5*ULN, estimated(est) creatinine clearance, est GFR modified and bedside schwartz, >1.0* ULN. Urinalysis: creatinine >1.0*ULN. | Baseline up to 104 days | 
| Absolute Values of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DSBP) in Participants |  | Baseline, Day 1, Day 2, Day 30, Day 60, Day 90 | 
| Absolute Values of Heart Rate (HR) and Pulse Rate (PR) of Participants | Heart rate and pulse rate of participants were measured in terms of beats per minute. | Baseline, Day 1, Day 2, Day 30, Day 60, Day 90 | 
| Absolute Values of Height of Participants |  | Baseline, Day 1, Day 2, Day 30, Day 60, Day 90 | 
| Absolute Values of Weight of Participants |  | Baseline, Day 1, Day 2, Day 30, Day 60, Day 90 | 
| Absolute Values of Respiratory Rate of Participants | Respiratory rate was defined as the number of breaths per minute. | Baseline, Day 1, Day 2, Day 30, Day 60, Day 90 | 
| Absolute Values of Body Temperature of Participants |  | Baseline, Day 1, Day 2, Day 30, Day 60, Day 90 | 
| Absolute Values of Body Length of Participants |  | Baseline, Day 1, Day 2, Day 30, Day 60, Day 90 | 
| Number of Participants With Physical Examination Abnormalities of Participants | Physical examinations included head, eyes, ears, nose, throat, neck, heart, chest, lungs, abdomen, extremities, skin, neurological status and general appearance. Abnormality in physical examination was based on investigator's discretion. Only those categories in which at least 1 participant had abnormality were reported. | Screening, Visit 2 (Baseline), Visit 3 (Day 1), Visit 4 (Day 2), Visit 5 (Day 30), Visit 6 (Day 60), Visit 7 (Day 90) | 
| Time to First Occurrence of Major Bleeding Event | Time to first occurrence of major bleeding event was defined as the time interval (in days) between date of first study treatment and 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: fatal bleeding, bleeding accompanied by a decrease in hemoglobin of at least 2 grams per deciliter, overt bleeding deemed by the attending physician to necessitate permanent discontinuation of trial medication, overt bleeding deemed by the attending physician to be unrelated to the participant's underlying condition and accompanied by blood product administration, bleeding occurred at a critical site (intraocular, intracranial, retroperitoneal or intraspinal). | Baseline up to 28 days after the last dose of study drug (up to Day 132) | 
| Percentage of Participants Who Remained Within Prespecified Therapeutic Anti-Factor Xa Levels at Day 30, 60 and 90 in Follow up Phase | Prespecified therapeutic anti-factor Xa level was 0.5-1.0 IU/mL. The percentage of participants who had anti factor-Xa levels within the prespecified therapeutic range at Day 30, 60 and 90 during the follow up phase were reported in this outcome measure. | Day 30, Day 60, Day 90 in follow up phase | 
| Percentage of Participants With Anti-Factor Xa Levels Outside the Prespecified Range at Day 30, 60 and 90 in Follow up Phase | Prespecified therapeutic anti-factor Xa range was 0.5-1.0 IU/mL. The percentage of participants who had anti-factor Xa levels outside the prespecified therapeutic range at Day 30, 60 and 90 during the follow up phase were reported in this outcome measure. | Day 30, Day 60, Day 90 in follow-up phase | 
| Maintenance Dose of Dalteparin Required to Achieve Prespecified Therapeutic Anti- Factor Xa Levels | Prespecified therapeutic anti-factor Xa level was 0.5-1.0 IU/mL. Cumulative data for day 1 to 7 has been reported. | 4 hours post-dose at each Day 1 to 7 in dose adjustment phase | 
| Time to Achieve Prespecified Therapeutic Anti- Factor Xa Levels | Time to achieve the target range (prespecified therapeutic anti- factor Xa levels) was defined as the number of days from the first dose of study drug to the final dose that achieves the target anti-factor Xa level. Prespecified therapeutic anti-factor Xa level was 0.5-1.0 IU/mL. Cumulative data of Day 1 to 7 is reported. | Day 1 to 7 in dose adjustment phase | 
| Number of Dose Adjustments Required to Achieve Prespecified Therapeutic Anti-Xa Levels | During dose adjustment phase, doses were adjusted according to prespecified therapeutic anti-Xa levels in order to achieve target prespecified therapeutic anti-factor Xa levels (0.5 to 1.0 IU/mL). Number of dose adjustments which were done within the specified time window of up to 4 hours post dose on all days (1 to 7) to achieve the prespecified therapeutic anti-Xa levels are reported. | 4 hours post-dose at each Day 1 to 7 in dose adjustment phase | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VTE