Vyxeos® and Clofarabine in relapsed/refractory pediatric AM

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 25

Inclusion Criteria

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 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 protocol 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 conditions:
•Lansky play score = 60; or Karnofsky performance status = 60
•Life expectancy > 6 weeks
•The patient must have a radioisotope GFR = 70mL/min/1.73 m2.
•Liver function: serum bilirubin =3 × upper limit of normal (ULN) and aspartate transaminase (AST)/alanine transaminase (ALT) =5×ULN
•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 presence of 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
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 during the study and for a minimum of 6 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

Exclusion Criteria

see inclusion criteria

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To establish the recommended phase 2 dose of Vyxeos®/CPX-351 in combination with clofarabine in children with relapsed/refractory AML

Secondary Outcome Measures

Name	Time	Method
•To determine the safety and tolerability of this combination<br>•To determine the (preliminary) efficacy in terms of the hematological remission rate in these patients as determined by morphology with flow cytometric confirmation.<br>•To describe the durability of response, including the number of patients that undergo stem- cell transplant after re-induction with this regimen