Effect of Fish Oil on Hyperlipidemia and Toxicities in Children and Young Adults With Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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Acute lymphoblastic leukemia (ALL) is the most common malignant disease among children. Treatment results have improved over time due to intensive risk-adapted therapy and the 5-year survival rate is now above 90%. However, the burden of therapy has increased proportionally. Many children develop serious acute and chronic side effects, which impact on the patients expected lifespan and impair their quality of life as a result of therapy. Treatment with PEG-asparaginase and dexamethasone increases the levels of triglycerides and total cholesterol. Consequently, the incidence of hyperlipidemia is high during initial ALL therapy. Studies have suggested that hyperlipidemia is a risk factor for development of osteonecrosis, thrombosis and possibly acute pancreatitis. Long-chained marine omega-3 fatty acids, found in fish oil, decrease levels of triglycerides and total cholesterol in hyperlipidemic patients. Due to the high survival rate, it is of great interest to develop methods to reduce treatment related toxicities. The investigators hypothesise that daily intake of fish oil will prevent development of hyperlipidemia during ALL treatment phases with dexamethasone and PEG-asparaginase compared to placebo and that fish oil intake may reduce the incidence of severe adverse events related to ALL treatment.

Official Title
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Effect of Fish Oil Versus Placebo on Hyperlipidemia and Toxicities in Children and Young Adults With Acute Lymphoblastic Leukemia - A Randomized Controlled Trial

Conditions
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Leukemia, Acute Lymphoblastic

Intervention / Treatment
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* Dietary Supplement: Eskimo-3 Pure Fish Oil
* Dietary Supplement: Rapeseed Oil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children (1-17.9 years) and young adults (18-45 years) diagnosed with ALL, stratified to very-low risk (VRL), intermediate risk low (IR-low) and intermediate risk high (IR-high) in the ALLTogether protocol. Exclusion Criteria: Patients diagnosed with ALL, stratified to high risk (HR) after induction treatment or stem cell transplantation in the ALLTogether protocol

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 45 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fish oil<br>Eskimo-3 Pure Fish Oil, 10 ml per day (2.6 g EPA+DHA) | Dietary Supplement: Eskimo-3 Pure Fish Oil<br>* Dosage: 10 ml/day (2.6 g EPA+DHA)<br>* Other names: Fish Oil;|
| Placebo Comparator: Placebo<br>Rapeseed Oil, 10 ml per day | Dietary Supplement: Rapeseed Oil<br>* Dosage: 10 ml/day (0 g EPA+DHA)<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hyperlipidemia | Triglycerides and/or total cholesterol levels five times or more than the age-dependent upper normal limit. | From treatment day 4 until treatment day 169 or 204 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lipid metabolism | Triglycerides, total cholesterol, VLDL-cholesterol, LDL-cholesterol and HDL-cholesterol. | VLR and IR-low: 4, 11, 18, 25, 32, 39, 46, 53, 60, 67, 81, 95, 109, 123, 137, 151 and 169. IR-high: treatment day 4, 11, 18, 25, 32, 39, 46, 53, 60, 67, 74, 81, 88, 95, 102, 109, 123, 137, 151, 165, 179, 193 and 204. | 
| Compliance | Assessed by self-registration forms, return of bottles and levels of EPA+DHA in whole blood | From treatment day 4 until end of intervention (treatment day 169 or 204) | 
| Bone density | Assessed by DEXA-scan and bone biomarkers (iCa, PTH, vit D, phosphate, magnesium, creatinine, alkaline phosphatase, CTX, P1NP. | DEXA-scan at start and end of intervention. Bone biomarkers at treatment day 4, 81 and 169 for VLR and treatment day 4, 102 and 204 for IR-low and IR-high. | 
| Hemostatic status | Thromboelastography (TEG), multiplate and thrombocytes. | At treatment day 4, 81 and 169 for VLR and at treatment day 4, 102 and 204 for IR-low and IR-high | 
| Endothelial function | sTM, syndecan-1, PECAM, VEGFR1 | At treatment day 4, 81 and 169 for VLR and at treatment day 4, 102 and 204 for IR-low and IR-high | 
| Incidence of severe adverse events | Cumulative incidence of osteonecrosis, asparaginase associated pancreatitis and thrombosis. | From treatment day 4 until end of intervention (treatment day 169 or 204) |