E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Leukaemia, Lymphoblastic, Acute and Lymphoma, Lymphoblastic |
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E.1.1.1 | Medical condition in easily understood language |
Leukaemia, Lymphoblastic, Acute and Lymphoma, Lymphoblastic |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 |
T o evaluate the safety and tolerability of nelarabine administered to Japanese patients with T-ALL or TLBL as a 2-hour intravenous infusion on a Day 1, 3 and 5 schedule for adult patients and as a 1-hour infusion on a Days 1-5 schedule for pediatric patients. |
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E.2.2 | Secondary objectives of the trial |
To determine the plasma pharmacokinetic (PK) profiles of nelarabine and ara-G when nelarabine is administered on these schedules.
•To determine intracellular ara-GTP concentrations when nelarabine is administered on these schedules*.
* Cohort 3 is established if possible at each of the centres. Determination of intracellular ara-GTP concentrations is not performed in subjects who have received induction therapy.
Primary Outcome/ |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histologic or cytogenetic documented diagnosis of T-ALL or T-LBL.
- Disease that is refractory to at least one prior chemotherapy regimen, or has relapsed following complete remission to at least one prior chemotherapy regimen.
- At least 4 weeks since the last dose of prior last chemotherapy, or radiotherapy before beginning treatment with 506U78 (2 weeks is permitted if growth of blast cells is significant).
- Adequate function of other organ systems as measured as follows.Serum creatinine is less than 1.5 times of upper limit of normal and estimated creatinine clearance >=50 mL/min. Hepatic transaminases (SGPT and SGOT) <=3 x upper limit of normal, bilirubin is less than 1.5 times of upper limit of normal(<=5 x upper limit of normal if it is related by T-ALL or T-LBL).
- Adequate performance status (ECOG-PS<=2).
- Capable of giving informed consent which includes compliance with the requirements and restrictions listed in the consent form.
- Patient is willing to accept hospitalization during the blood sampling for pharmacokinetic measurement (i.e., Cohort 1: for pharmacokinetic sample collection during both cycle 1 and 2; and Cohort 2: for pharmacokinetic sample collection during cycle 1).
- Female subjects who are of child-bearing potential must have a negative pregnancy test at the Screening Visit and agree to utilize contraceptive methods during participation in the study and for at least six months following the last dose of 506U78 Injection. Female subjects may be defined as of non-child-bearing potential if they are physiologically incapable of becoming pregnant, including any female who is post-menopausal. For purposes of this study, postmenopausal is defined as one year without menses. |
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E.4 | Principal exclusion criteria |
- Active infection at time of treatment.
- Concurrent disease or condition that would make the subject inappropriate for study participation.
- Receiving any other anticancer agents or enrolled on any investigational study during the course of the study.
- Patients must have recovered to Grade I or less toxicity of all previous chemotherapy prior to treatment.
- History of seizure disorder within one year prior to the date of informed consent.
- Pregnancy (as demonstrated by a positive pregnancy test at pre-study/screening) or breastfeeding. Fertile women and men must practice adequate contraception throughout the study and at least 6 month after the last dose of study drug. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Safety and tolerability: Adverse events (AEs), physical examinations, laboratory tests, 12-lead ECG
• Plasma PK parameters (e.g., AUC, Cmax) for nelarabine and ara-G
• Intracellular ara-GTP concentrations (e.g., Cmax, trough level) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
2-hour intravenous infusion on a Day 1, 3 and 5 schedule for adult patients and as a 1-hour
Infusion on a Days 1-5 schedule for pediatric patients. |
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E.5.2 | Secondary end point(s) |
Percentage of subjects with complete response with and without hematologic recovery (CR and CR*, respectively) in the assessment of best overall response |
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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 | 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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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) | 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 | 5 |
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 years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |