Relapsed or refractory pediatric acute myeloid leukemia MedDRA version: 21.0 Level: LLT Classification code 10060558 Term: Acute myeloid leukemia recurrent System Organ Class: 100000004864 MedDRA version: 21.1 Level: LLT Classification code 10081514 Term: Acute myeloid leukemia refractory System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Vyxeos liposomal
Product Name: Vyxeos liposomal
Product Code: CPX-351
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Daunorubicin
CAS Number: 20
Sponsors
Princess Máxima Center for pediatric oncology
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age =1 year and 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 Are the trial subjects under 18? yes Number of subjects for this age range: 25 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 3 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 • Known copper metabolism deficiency, such as Wilson's disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To establish the recommended phase 2 dose of Vyxeos®/CPX-351 in combination with clofarabine in children with relapsed/refractory AML ;Secondary Objective: • To determine the safety and tolerability of this combination. • To determine the (preliminary) efficacy in terms of the hematological remission rate in these patients as determined by morphology with flow cytometric confirmation. • To describe the durability of response, including the number of patients that undergo stem- cell transplant after re-induction with this regimen ;Primary end point(s): Dose-limiting toxicities (DLTs) during the first course of therapy. ;Timepoint(s) of evaluation of this end point: DLT evaluation after course 1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • safety and tolerability of combination clofarabine with Vyxeos/CPX-351 • hematological remission rate • overall response rate (ORR) • number of patients that undergo HSCT Exploratory endpoints: • serum and intracellular pharmacokinetics parameters of Vyxeos/CPX-351 • relationship ORR and intracellular Ara-CTP accumulation • correlation duration of response and MRD;Timepoint(s) of evaluation of this end point: • After course 1, after each subsequent course of therapy, and at 4wks, 10wks, 3months, 6 months and 9 months, 12 months, 18 months and 24 months of FUP • end of study (EOS) | — |
Countries
Austria, Denmark, Germany, Italy, Netherlands, Spain
Contacts
Public ContactTrialmanagement
Princess Máxima Center for pediatric oncology
Outcome results
None listed