A Phase I/II study of clofarabine in combination with cytarabine and liposomal daunorubicin in children with relapsed/refractory pediatric AML - CLARA-DNX

• Register: EUCTR
• Last refreshed on: 17 August 2015
• Main ID: EUCTR2009-009457-13-AT
• Date of registration: 28/12/2009
• Prospective Registration: Yes
• Primary sponsor: Erasmus MC
• Public title: A Phase I/II study of clofarabine in combination with cytarabine and liposomal daunorubicin in children with relapsed/refractory pediatric AML - CLARA-DNX
• Scientific title: A Phase I/II study of clofarabine in combination with cytarabine and liposomal daunorubicin in children with relapsed/refractory pediatric AML - CLARA-DNX
• Date of first enrolment: 28/01/2010
• Target sample size: 28
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-009457-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Austria, Czech Republic, France, Germany, Netherlands

Key inclusion & exclusion criteria

Inclusion criteria:
• 2nd relapse of AML
• refractory AML in 1st relapse (defined as = 20% blasts in the bone marrow after the 1st course of re-induction therapy according to the AML 2001/01 protocol)
• 1st early relapse (relapse within one year from initial diagnosis) of AML (only when the Relapsed AML 2001/01 study is closed)
• = 18 years old at initial diagnosis
• Lansky play score > 60; or Karnofsky performance status > 60
• Life expectancy > 6 weeks
• Calculated creatinine clearance = 90 ml/min/1.73m2 as calculated by the Schwartz formula for estimated glomerular filtration rate (GFR) where GFR (ml/min/1.73 m2) = k*Height (cm)/serum creatinine (mg/dl). k is a proportionality constant which varies with age and is a function of urinary creatinine excretion per unit of body size; 0.45 up to 12 months of age; 0.55 children and adolescent girls; and 0.70 adolescent boys.
• Liver function:
Serum bilirubin =1.5 × upper limit of normal (ULN)
Aspartate transaminase (AST)/alanine transaminase (ALT) <2.5 × ULN
Alkaline phosphatase <2.5 × ULN
• Able to comply with scheduled follow-up and with management of toxicity.
• For female patients with childbearing potential, a negative test for pregnancy is to be considered before entry on study
• Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.
• Written informed consent from patients or from parents or legal guardians for minor patients, according to local law and regulations


Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Isolated extramedullary relapse, including isolated CNS-relapse
• Symptomatic CNS leukemia in case of combined relapse
• Relapsed/refractory acute promyelocytic leukemia (APL)
• Relapsed/refractory myeloid leukemia of Down Syndrome (ML DS)
• Other serious illnesses or medical conditions
• Current uncontrolled infection
• Evidence of cardiac dysfunction (shortening fraction below 28%)
• Pregnant or lactating patients
Prior or current history:
• 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)
• Hypersensitivity to cytarabine, clofarabine or liposomal daunorubicin



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Relapsed/refractory acute myeloid leukemia
MedDRA version: 9.1 Level: LLT Classification code 10060558 Term: Acute myeloid leukemia recurrent
MedDRA version: 9.1 Level: LLT Classification code 10066638 Term: Acute myeloid leukemia progression

Intervention(s)

Trade Name: Evoltra 1 mg/ml concentrate for solution for infusion
Product Name: Evoltra
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: CLOFARABINE
CAS Number: 123318-82-1
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20mg/20ml-

Trade Name: Cytarabine 100 mg/ml (off patent generic drug)
Product Name: Cytarabine
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: CYTARABINE
CAS Number: 147-94-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100mg/ml-

Trade Name: DaunoXome
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: DAUNORUBICIN
CAS Number: 20830813
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2mg/ml-

Primary Outcome(s)

Primary end point(s): To identify the recommended dose of the combination of clofarabine, cytarabien an dliposomal daunorubicin in relapsed/refractory AML, hence to identify dose-limiting toxicities and the MTD.

Secondary Objective: - To determine the safety and tolerability of this combination
- To determine (preliminary) efficacy in terms of the hematological remission rate in these patients
- To describe the durability of response, including the number of patients that undergo stem-cell transplant after re-induction with this regimen
- To describe the pharmacokinetics of clofarabine in combination with cytarabine and liposomal daunorubicin
- To preliminary assess the CSF blast disappearance, and the CSF-levels of clofarabine

Main Objective: To establish the recommended dose of clofarabine in combination with cytarabine and liposomal daunorubicin (DaunoXome®) in children with relapsed/refractory AML.

Note: dosages of cytarabine and liposomal daunorubicin should be comparable to those used in the current Relapsed AML 2001/01 study (i.e. in the context of the FLAG/liposomal daunorubicin regimen).

Secondary ID(s)

Study ITCC 020 & I-BFM Relapsed AML

2009-009457-13-NL