E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020907 |
E.1.2 | Term | Hyperuricemia |
E.1.2 | System Organ Class | 100000004861 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate safety of rasburicase in pediatric patients with NHL and AL |
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E.2.2 | Secondary objectives of the trial |
To assess efficacy of rasburicase for prevention and treatment of hyperuricemia |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- The patient or parent/legal guardian is willing and able to provide signed informed consent, and if required, the patient is willing to provide assent. - Children or adolescent aged 2 to 18 years old (inclusive) at time of signing of informed consent. - At screening, the patient is expected to have a minimum life expectancy of 45 days and has a performance status (PS) ≤ 3 on the Eastern Cooperative Oncology Group (ECOG) scale, or a PS ≥ 30 on the Lansky score as per the Investigator’s preference. - Newly diagnosed NHL or AL who is at the initiation of or during the first cycle of chemotherapy, baseline blood uric acid >8 mg/dL (473 μmol/L) at screening. - If newly diagnosed NHL patient with blood uric acid ≤ 8 mg/dL at screening, the patient must be diagnosed with Stage III or IV non-Hodgkin’s lymphoma with high tumor burden which will be high risk of TLS (Tumor lysis syndrome). - If newly diagnosed AL patient is with blood uric acid ≤ 8 mg/dL at the screening but with a high risk of TLS. - The patient will receive the chemotherapy, and will be confined in hospital for at least 14 days after first dose of rasburicase. |
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E.4 | Principal exclusion criteria |
- Acute promyelocytic leukemia - Patient who has been treated or planned to receive allopurinol within 72 hours of rasburicase administration. - Patients with abnormal liver or renal function. - Documented history of hereditary allergy or asthma. - Patients with known deficiency of glucose-6-phosphate dehydrogenase (G6PD), or a history of hemolytic disease or methemoglobinemia. - Patients with severe infection or active bleeding. - Previous therapy with urate oxidase. - Hypersensitive reaction against rasburicase or any of the other ingredients of the study drug. - Patient is not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or patients potentially at risk of noncompliance to study procedures. - Pregnant or breastfeeding woman. - Woman of childbearing potential (WOCBP) not protected by highly-effective method(s) of birth control and/or who are unwilling or unable to be tested for pregnancy. - Male participant with a female partner of childbearing potential not protected by highly-effective method(s) of birth control. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of AEs and SAEs : Incidence of AE or SAE will be summarized as the number and percentage of subjects who experienced any AE or SAE during the treatment period. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1)Number of responders after completion of rasburicase treatment under chemotherapy: Response will be defined as achievement of normal uric acid levels (≤ 8.0 mg/dL) in those patients whose uric acid levels are >8.0 mg/dL 2)Proportion of patients who can maintain the normal uric acid levels throughout the study: In those patients whose baseline plasma uric acid levels are ≤ 8 mg/dL but with a high risk of TLS 3)Percentage of the maximum decreasing degree of plasma uric acid level from baseline |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial months | 11 |