Pilot Study Efficacy and Tolerance Fish Oil Emulsion Daunorubicin and Cytarabine Treatment of AML Younger Patients

Study Overview
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Brief Summary
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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
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Adjunction of a Fish oil emulsion OMEGAVEN to daunorubicin and cytarabine chemotherapy for the treatment of Acute MYeloblastic Leukemia of Younger patients.

Official Title
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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

Conditions
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Acute Myeloid Leukemia (AML)

Intervention / Treatment
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* Drug: OMEGAVEN
* Drug: Daunorubicin
* Drug: Cytarabine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 61 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 |
| --- | --- |
| Experimental: OMEGAVEN - Daunorubicin - Cytarabine<br>If WBC ≥ 30 G/L, chemotherapy the induction cycle : Daunorubicin 60 mg/m²/day IV on D1, D2, and D3 Cytarabine 200 mg/m²/day D1 to D7 OMEGAVEN® 2 ml/kg D1 to D9, If WBC ≤ 30 G/L, OMEGAVEN during 48 hours Induction cycle : OMEGAVEN® 2 ml/kg D-2 to D7 Daunorubicin 60 mg/m²/day IV on D1, D2, and D3 - Cytarabine 200 mg/m²/day IV D1 to D7 bone marrow aspirate at D15: If BM blasts are > 5% or if second induction course : Daunorubicin 35 mg/m²/day IV D17 and D18 OMEGAVEN® 2 ml/kg Cytarabine 1000 mg/m²/12h IV on D17, D18, and D19 For all patients: G-CSF 5 µg/kg/day subcutaneously from D21 to hematopoietic recovery (PMN > 1 G/L or > 0.5 G/L during 3 days). Consolidation will be administered at investigator's discretion | Drug: OMEGAVEN<br>* AML Study treatment induction phase<br>Drug: Daunorubicin<br>* AML Study treatment induction phase<br>* Other names: Cerubidine;Drug: Cytarabine<br>* AML Study treatment induction phase<br>* Other names: Aracytine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| response to study treatment | Number of patients incomplete response rate after the adjunction of a Fish oil emulsion to daunorubicin and cytarabine chemotherapy for the induction of untreated AML | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerance | Number of patients with side effects during and after the admistration of a Fish oil emulsion with daunorubicin and cytarabine chemotherapy for the induction of untreated AML | 4 months | 
| Efficacy on peripheral blasts decrease | Daily quantification of peripheral blasts by flow cytometry during the adjunction of a Fish oil emulsion to daunorubicin and cytarabine chemotherapy | 1 month | 
| pharmacokinetics | Measure of plasma concentration of daunorubicin and cytarabine administered together with a fish oil emulsion | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML, high-risk cytogenetics, younger patients, Induction treatment, OMEGAVEN