A Phase Ib study of Vyxeos® (liposomal daunorubicin and cytarabine) in combination with Clofarabine in children with relapsed/refractory AML, ITCC-092

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 5

Inclusion Criteria

• Age >=1 year and <=21 years
• 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 allogeneic HSCT
• Any relapse of AML with high risk cytogenetic characteristics (as defined in
Appendix V)

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

• 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.
• Female patients may not breastfeed 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, 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

• Evidence of a currently uncontrolled bacterial, viral or parasitic infection
• 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)
• Evidence of isolated extramedullary relapse, including isolated CNS-relapse
• Evidence of CNS3 or symptomatic CNS leukemia
• Down Syndrome
• Evidence of relapsed/refractory acute promyelocytic leukemia (APL)
• 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)
• History of prior veno-occlusive disease (VOD)
• Known hypersensitivity to cytarabine, clofarabine or liposomal daunorubicin
• Copper metabolism deficiency, such as Wilson's disease

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Frequency of Dose-limiting toxicities (DLTs) during the first course of<br /><br>therapy. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>1. Safety and tolerability: frequency of AEs, frequency of laboratory<br /><br>abnormalities and number of toxic deaths<br /><br>2. Measures of anti-leukemic activity: ORR after 1 course and as best response<br /><br>and ORR after 2 courses, which includes CR, CRi, and PR, determined by<br /><br>morphology with flow cytometric confirmation.<br /><br>3. Overall patient survival (OS) and relapse-free survival<br /><br>4. Number of patients undergoing HSCT after treatment<br /><br><br /><br>Exploratory endpoints:<br /><br>5. Serum and intracellular (as Ara-CTP accumulation in leukemic blasts)<br /><br>pharmacokinetic parameters<br /><br>6. Relationship between response (ORR) and Ara-CTP accumulation<br /><br>7. Correlation between duration of response and measurable residual disease<br /><br>(MRD) assessed by Flow-cytometry</p><br>