Leukemia, Acute Lymphoblastic
Conditions
Brief summary
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.
Interventions
DIETARY_SUPPLEMENTEskimo-3 Pure Fish Oil
Dosage: 10 ml/day (2.6 g EPA+DHA)
DIETARY_SUPPLEMENTRapeseed Oil
Dosage: 10 ml/day (0 g EPA+DHA)
Sponsors
Danish Child Cancer Foundation
Rigshospitalet, Denmark
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Years to 45 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hyperlipidemia | From treatment day 4 until treatment day 169 or 204 | Triglycerides and/or total cholesterol levels five times or more than the age-dependent upper normal limit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lipid metabolism | 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. | Triglycerides, total cholesterol, VLDL-cholesterol, LDL-cholesterol and HDL-cholesterol. |
| Compliance | From treatment day 4 until end of intervention (treatment day 169 or 204) | Assessed by self-registration forms, return of bottles and levels of EPA+DHA in whole blood |
| Bone density | 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. | Assessed by DEXA-scan and bone biomarkers (iCa, PTH, vit D, phosphate, magnesium, creatinine, alkaline phosphatase, CTX, P1NP. |
| Endothelial function | At treatment day 4, 81 and 169 for VLR and at treatment day 4, 102 and 204 for IR-low and IR-high | sTM, syndecan-1, PECAM, VEGFR1 |
| Incidence of severe adverse events | From treatment day 4 until end of intervention (treatment day 169 or 204) | Cumulative incidence of osteonecrosis, asparaginase associated pancreatitis and thrombosis. |
| Hemostatic status | At treatment day 4, 81 and 169 for VLR and at treatment day 4, 102 and 204 for IR-low and IR-high | Thromboelastography (TEG), multiplate and thrombocytes. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Milder side effects | At end of intervention (day 169 or 204) | Assessed by questionnaire. |
| Dietary intake | At treatment day 4, 81 and 169 for VLR and at treatment day 4, 102 and 204 for IR-low and IR-high | Assessed by 3-day food records |
Countries
Denmark
Contacts
Primary ContactRenate Dagsdottir Laumann, MSc
Outcome results
None listed