New hope for kids with tough leukemia: drug combo trial launches

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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. NL72866.041.20 / Vyxeos liposomal and Clofarabine in R/R pediatric AML - ITCC-092 Protocol version: 2.2, 08-04-2021 38 of 80 * 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.