E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Lymphoblastic Leukemia
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E.1.1.1 | Medical condition in easily understood language |
Acute Lymphoblastic Leukemia
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000845 |
E.1.2 | Term | Acute lymphoblastic leukemia |
E.1.2 | System Organ Class | 100000004864 |
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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 assess the safety, tolerability and pharmacokinetics (PK) of clofarabine administered intravenously to pediatric patients with relapsed or refractory acute lymphoblastic leukemia (ALL) or for whom no other therapy with greater potential clinical benefit exists. The dosing regimen for the intravenous (IV) clofarabine was 30 or 52 mg/m2/day for 5 consecutive days |
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E.2.2 | Secondary objectives of the trial |
To document the activity of clofarabine and to explore the impact of deoxycytudune kinase (dCK) promoter polymorphism on PK and treatment outcome. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Signed and written informed consent provided by patients ≥ 20 years old or by the parents or guardians of patients less than 20 years old. Investigator should verbally obtain informed assent from the patients 7 years old or older and written informed assent from patients 12 years old or older.
•Greater than or equal to 25 percent blasts present in the bone marrow and/or peripheral blood count and diagnosed with ALL .at time of enrollment
•Patients with relapsed or refractory ALL. Patients must not be eligible for therapy of higher clinical benefit potential and must be in second or subsequent relapse and/or refractory, i.e. failed to achieve remission following 2 or more different regimens, or for whom no other therapy with greater potential clinical benefit exists.
•Have a Karnofsky Performance Status of greater than or equal to 70 for patients 10 years of age or older or Lansky Performance Status greater than or equal to 70 for patients below 10 years of age.
•Patients whose hepatic, renal, and pancreatic functional tests are within the ranges defined in the protocol |
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E.4 | Principal exclusion criteria |
•Received previous treatment with clofarabine.
•Have received any other investigational agent within 30 days prior to the first dose of the study drug.
•Have received any other chemotherapy within 14 days prior to the first dose of clofarabine. However, intrathecal drug administration is allowed up to 24 hours prior to the first dose of clofarabine. In addition, the patient must have been recovered from acute toxicity related to other chemotherapy or investigational agents (baseline or less than or equal to Common Terminology Criteria for Adverse Events ver 3.0 Grade 1)
•Have systemic fungal, bacterial, viral, or other infection that cannot be controlled(defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment). In addition, for patients with a history of fever (≥38.5˚C) within the preceding 3 days at the time of enrollment, documentation of negative blood cultures for at least 48 hours required.
•Have a psychiatric disorder that would interfere with consent, study participation, or follow-up.
•Patients whose spinal fluid tested immediately before the study registration within 7 days before dose indicates symptomatic Central Nervous System (CNS) involvement (i.e.CNS3).
•Have any other severe concurrent disease or a history of serious organ dysfunction or disease involving the heart, kidney, liver, or pancreas.
•Have received hematopoietic stem cell transplantation (HSCT) within 3 months prior to providing the consent or have acute graft-versus-host disease (GVHD) (greater than or equal to Grade 2) requiring immunosuppressive therapy or severe (systemic) chronic GVHD.
•Have a prior positive test for Hepatitis B surface (HBs) antigen or antibody, HBc antibody, Hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antibody. (The patients who have had treatment of vaccine and are positive for HBs antibody are eligible).
•Are pregnant or nursing. Male and female patients of reproductive potential must agree to use an effective means of birth control to avoid pregnancy during the study period and for 180 days after the last dose of study drug.
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E.5 End points |
E.5.1 | Primary end point(s) |
•Maximum Tolerated Dose (MTD)
•Safety as evaluated by adverse events (incidence, severity, duration, causality, seriousness, type)
•Pharmacokinetics as measured by maximum drug serum concentration (Cmax)
•Pharmacokinetics as measured by Time to maximum serum concentration (Tmax)
•Pharmacokinetics as measured by Area Under the drug-concentration curve (AUC)
•Pharmacokinetics as measured by half life (t1/2)
•Pharmacokinetics as measured by renal clearance (CLr)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
•Safety as evaluated by adverse events (incidence, severity, duration, causality, seriousness, type): 45 days after final study drug administration
•Pharmacokinetics as measured by maximum drug serum concentration (Cmax): Day 1 to Day 5
•Pharmacokinetics as measured by Time to maximum serum concentration (Tmax): Day 1 to Day 5
•Pharmacokinetics as measured by Area Under the drug-concentration curve (AUC): Day 1 to Day 5
•Pharmacokinetics as measured by half life (t1/2): Day 1 to Day 5
•Pharmacokinetics as measured by renal clearance (CLr): Day 1 to Day 5
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E.5.2 | Secondary end point(s) |
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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 | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
A Phase 1, Open-label, Multi-center Study of Clofarabine in Japanese Pediatric Patients |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
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 | No |
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 | Yes |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 5 |