Vyxeos® With Clofarabine for Pediatric AML

We will include pediatric patients ≥1 year and ≤21 years with:

• Any ≥ 2nd relapse of AML
• Refractory AML (defined as ≥ 20% blasts in the bone marrow after standard (re-) induction therapy)
• Early 1st relapse (defined as relapse within one year from initial diagnosis) of AML
• Any relapse of AML after prior allogenic HSCT
• Any relapse of AML with high risk cytogenetic characteristics (as defined in Appendix V)

In order to be eligible to participate in this study, a subject must meet all of the following criteria:

Initial work-up:

• Complete initial work-up within 7 days prior to study entry, including bone-marrow aspiration, lumbar puncture (without intrathecal therapy)

General condition:

• Lansky play score ≥ 60 for patients <16 years of age; or Karnofsky performance status ≥ 60 for patients ≥ 16 years of age (see Appendix I for Performance scales).
• Life expectancy > 6 weeks
• The patient must have a calculated GFR ≥ 70mL/min/1.73 m2.
• Liver function: total serum bilirubin ≤ 3 mg/dl or 50 μmol/L and aspartate transaminase (AST) and alanine transaminase (ALT) ≤200 U/L
• Adequate cardiac function (defined as shortening fraction ≥28% or ejection fraction ≥50%)
• No evidence of a currently uncontrolled bacterial, viral or parasitic infection
• No evidence of a fungal infection, defined as either:

• Pulmonary infiltrates suggestive of a fungal infection at HR-CT (within 3 weeks prior to enrollment)
• Positive Aspergillus serum test (galactomannan), according to local laboratory practice (within 3 weeks prior to enrollment)
• No evidence of isolated extramedullary relapse, including isolated CNS-relapse
• No evidence of CNS3 or symptomatic CNS leukemia
• No Down Syndrome
• No evidence of relapsed/refractory acute promyelocytic leukemia (APL)
• No use of any anticancer therapy within 2 weeks before study entry. The patient must have recovered from all acute toxicities from any previous therapy (note: hematological toxicities do not need to be considered since the patient has overt leukemia)
• No history of prior veno-occlusive disease (VOD)
• No known hypersensitivity to cytarabine, clofarabine or liposomal daunorubicin
• No known copper metabolism deficiency, such as Wilson's disease.

Other:

• For female patients with childbearing potential, a negative test for pregnancy is to be performed before entry on study.
• Male and female patients must use a highly effective contraceptive method according to the CTFG 2014-guidelines during the study and for a minimum of 6 months after study treatment.

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• Female patients may not breast feed during the study and for a minimum of 3 months after study treatment.
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule is required; those conditions should be discussed with the patient before registration in the trial.
• Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.

Concomitant treatments:

• Concomitant administration of any other experimental drug under investigation, or concurrent treatment with any other anti-cancer therapy other than specified in the protocol is not allowed.
• GCSF will not be used for priming and no routine GCSF support is allowed during the 1st course, except for life-threatening infections.

Additional criteria:

• At least 6 patients must be enrolled with an M3 or a WBC count >10x109/L with blasts.