relapsed/refractory pediatric acute myeloid leukemia
Conditions
Interventions
Treatment will consist of 2 courses. A combination of Vyxeos®/CPX-351 given at
day 1, 3, 5 with clofarabine given at day 2-6 will be administered in course 1,
and Vyxeos®/CPX-351 only in course 2.
Sponsors
Prinses Máxima Centrum voor Kinderoncologie
Eligibility
Age
2 Years to 99 Years
Inclusion criteria
Inclusion criteria: • Age >=1 year and = 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 = 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 =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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Frequency of Dose-limiting toxicities (DLTs) during the first course of therapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Safety and tolerability: frequency of AEs, frequency of laboratory abnormalities and number of toxic deaths 2. Measures of anti-leukemic activity: ORR after 1 course and as best response and ORR after 2 courses, which includes CR, CRi, and PR, determined by morphology with flow cytometric confirmation. 3. Overall patient survival (OS) and relapse-free survival 4. Number of patients undergoing HSCT after treatment Exploratory endpoints: 5. Serum and intracellular (as Ara-CTP accumulation in leukemic blasts) pharmacokinetic parameters 6. Relationship between response (ORR) and Ara-CTP accumulation 7. Correlation between duration of response and measurable residual disease (MRD) assessed by Flow-cytometry | — |
Countries
Netherlands
Outcome results
None listed