Clinical trial NCT01999413: Pilot Study Efficacy and Tolerance Fish Oil Emulsion Daunorubicin and Cytarabine Treatment of AML Younger Patients
Official title: Pilot Study of the Efficacy and Tolerance of the Adjunction of a Fish Oil Emulsion to Daunorubicin and Cytarabine Chemotherapy for the Treatment of Acute MYeloblastic Leukemia of Younger Patients With High-risk Cytogenetics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia (AML)
Keywords: AML
high-risk cytogenetics
younger patients
Induction treatment
OMEGAVEN
Lead sponsor: French Innovative Leukemia Organisation
Sponsor class: OTHER
Collaborators: name: Fresenius Kabi
First posted: 2013-12-03
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 61
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Pilot study of the efficacy and tolerance of the adjunction of a Fish oil emulsion to daunorubicin and cytarabine chemotherapy for the treatment of Acute MYeloblastic Leukemia of Younger patients (under 61 years) with high-risk cytogenetics.

Detailed description: Adjunction of a Fish oil emulsion OMEGAVEN to daunorubicin and cytarabine chemotherapy for the treatment of Acute MYeloblastic Leukemia of Younger patients.

Eligibility criteria: Inclusion Criteria:

* Patient between 18 and 60 years old (less than 61 years old)
* With newly diagnosed with AML according to WHO classification:
* With 20% or more blasts in the bone marrow
* Patients with history of tumors other than myeloproliferative disorders or myelodysplastic syndromes, having received chemotherapy and/or radiotherapy without previous history of myelodysplastic syndromes are eligible for the present study
* High-risk cytogenetics defined as one the following abnormalities : 5/5q-, 7/7q-, t(6,9), 11q23 abnormality excluding t(9;11), 3q abnormality,complex karyotype (\>3 abnormalites)
* Left ventricular ejection fraction (LVEF) \> 50% on echocardiography or multigated acquisition (MUGA) scan or similar radionuclide angiographic scan.
* Adequate liver function (all of the following) except if secondary to the leukemia:

Total bilirubin below 1.5 x upper limit of normal (ULN), AST and ALT below 2.5 x ULN , gamma-GT below 2.5 x ULN,

* Adequate kidney function (all of the following): Serum creatinine below 1.5 x ULN, Creatinine clearance above 50 mL/min (Cockroft and Gault formula)
* ECOG performance status \< or = 2.
* Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
* The patient must give written (personally signed and dated) informed consent before completing any study-related procedure which means assessment or evaluation that would not form part of the normal medical care of the patient.
* Affiliated to the French Social Security (Health Insurance).

Exclusion Criteria:

* Previous allogeneic stem cell transplantation.
* Pre-existing aplastic anemia
* Presence of favourable cytogenetics with t(8;21), t(15;17), or inv(16)
* Previous history of MDS or myeloproliferative neoplasm
* Uncontrolled active infection.
* History of arrythmia.
* Cardiac toxicity induced by another anthracycline administration
* Maximum cumulative dose reached for any anthracyclin
* Allergy to cytarabine, daunorubicin, fish or egg proteins10. Significant neurologic (grade \> 2) or psychiatric disorder, dementia or seizures.
* Clinical symptoms suggesting active central nervous system leukemia.
* Degenerative or toxic encephalopathy
* Severe complications of leukemia such as:Uncontrolled bleeding, Pneumonia with hypoxia or shock
* Prior total body irradiation \> 10 Gy.
* Known active HIV, Hepatitis B or C infection
* Pregnancy or breastfeeding
* Concomitant anti-amarile vaccination (yellow fever)
* Concurrent treatment with any other anti-cancer therapy except Hydroxyurea

Primary outcomes:
measure: response to study treatment
timeFrame: 1 month
Secondary outcomes:
measure: Tolerance
timeFrame: 4 months
measure: Efficacy on peripheral blasts decrease
timeFrame: 1 month
measure: pharmacokinetics
timeFrame: 1 month
Other outcomes:
Locations:
city: Tours
country: France
facility: Emmanuel GYAN
Study officials:
affiliation: French Innovative Leukemia Organisation
name: Emmanuel GYAN, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gyan E, Pigneux A, Hunault M, Peterlin P, Carre M, Bay JO, Bonmati C, Gallego-Hernanz MP, Lioure B, Bertrand P, Vallet N, Ternant D, Darrouzain F, Picou F, Bene MC, Recher C, Herault O. Adjunction of a fish oil emulsion to cytarabine and daunorubicin induction chemotherapy in high-risk AML. Sci Rep. 2022 Jun 13;12(1):9748. doi: 10.1038/s41598-022-13626-y.
citation: Picou F, Debeissat C, Bourgeais J, Gallay N, Ferrie E, Foucault A, Ravalet N, Maciejewski A, Vallet N, Ducrocq E, Haddaoui L, Domenech J, Herault O, Gyan E. n-3 Polyunsaturated fatty acids induce acute myeloid leukemia cell death associated with mitochondrial glycolytic switch and Nrf2 pathway activation. Pharmacol Res. 2018 Oct;136:45-55. doi: 10.1016/j.phrs.2018.08.015. Epub 2018 Aug 22.
citation: Gyan E, Raynard B, Durand JP, Lacau Saint Guily J, Gouy S, Movschin ML, Khemissa F, Flori N, Oziel-Taieb S, Bannier Braticevic C, Zeanandin G, Hebert C, Savinelli F, Goldwasser F, Hebuterne X; NutriCancer2012 Investigator Group. Malnutrition in Patients With Cancer: Comparison of Perceptions by Patients, Relatives, and Physicians-Results of the NutriCancer2012 Study. JPEN J Parenter Enteral Nutr. 2018 Jan;42(1):255-260. doi: 10.1177/0148607116688881. Epub 2017 Dec 11.