Vyxeos plus clofarabine for relapsed or refractory pediatric AML

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This Phase 1, multi-center trial gives combined Vyxeos (liposomal daunorubicin and cytarabine) and clofarabine to pediatric patients with relapsed or refractory AML to determine safety, tolerability, and an appropriate dose. The rationale is that clofarabine inhibits ribonucleotide reductase, depleting normal deoxynucleotides and increasing Ara‑CTP levels to potentially boost cytarabine’s cytotoxicity delivered via liposomal Vyxeos. Eligible patients must meet defined relapse or refractory criteria and baseline organ-function and performance requirements before receiving treatment. The trial is led by the Princess Maxima Center with participating sites in Vienna, Copenhagen, and Augsburg, and will inform recommended dosing and early signals of activity for future studies.

Why it matters

Who can join: the full rules

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.

Where it's running

• St. Anna Kinderspital
  Vienna, Austria Recruiting
• Rigshospitalet
  Copenhagen, Denmark Recruiting
• Universitätsklinikum Augsburg
  Augsburg, Germany Recruiting
• Charité Berlin
  Berlin, Germany Recruiting
• University Children´s Hospital III Essen
  Essen, Germany Recruiting
• Universitätsklinikum Frankfurt
  Frankfurt, Germany Recruiting

Study contacts

• Principal investigator: C.M. Zwaan, Prof. dr. — Princess Maxima Center
• Study coordinator: Loes Meijs
• Email: L.A.M.Meijs-3@prinsesmaximacentrum.nl
• Phone: +31 6 50173349

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.