Vyxeos plus clofarabine for relapsed or refractory pediatric AML

A Phase lb Study of Vyxeos® (Liposomal Daunorubicin and Cytarabine) in Combination With Clofarabine in Children With Relapsed/Refractory AML, ITCC-092

This trial tries combining Vyxeos (liposomal daunorubicin/cytarabine) with clofarabine to treat children and young adults aged 1–21 with relapsed or refractory AML.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 1 Year to 21 Years
• Sex: All
• Sponsor: Princess Maxima Center for Pediatric Oncology (other)
• Drugs / interventions: chemotherapy, fludarabine
• Locations: 13 sites (Vienna and 12 other locations)
• Trial ID: NCT07156435 on ClinicalTrials.gov

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.

Who should consider this trial

Good fit: Children and young adults aged 1–21 with relapsed or refractory AML — including early first relapse, second or greater relapse, relapse after prior allogeneic HSCT, or high‑risk cytogenetics — who meet performance and organ‑function criteria are the intended candidates.

Not a fit: Newly diagnosed patients in first remission, those with poor performance status, or those with inadequate renal or hepatic function (below protocol thresholds) are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, the combination could increase remission rates and help more children reach potentially curative stem‑cell transplantation.

How similar studies have performed: Earlier early‑phase trials pairing clofarabine with cytarabine or fludarabine‑based regimens showed promising responses in relapsed pediatric AML, but combining clofarabine specifically with Vyxeos is a novel approach.

Eligibility 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 (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 this trial is running

Vienna and 12 other locations

• 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)
• Universitätsklinikum Hamburg-Eppendorf — Hamburg, Germany (RECRUITING)
• Clinica Pediatrica Fondazione MBBM — Monza, Italy (RECRUITING)
• Ospedale Pediatrico Bambino Gesu (OPBG) — Roma, Italy (RECRUITING)
• Princess Maxima Center — Utrecht, Utrecht, Netherlands (RECRUITING)
• Hospital Sant Joan de Déu — Barcelona, Spain (RECRUITING)
• Hospital Vall D'Hebron — Barcelona, Spain (RECRUITING)
• Hospital Infantil Universitario Niño Jesús — Madrid, Spain (RECRUITING)

Study contacts

• Principal investigator: C.M. Zwaan, Prof. dr. — Princess Maxima Center
• Study coordinator: Loes Meijs

Conditions: Relapsed Pediatric AML, Refractory Pediatric AML, pediatric AML, relapsed/refractory, clofarabine, liposomal daunorubicin and cytarabine