E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
T-cell leukemia (precursor T-lymphoblastic leukemia/lymphoma ot T-PLL). |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036543 |
E.1.2 | Term | Precursor T-lymphoblastic lymphoma/leukaemia |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the sustained effectivenes (for a minimum of 28 days) of intravenous (IV) Forodesine Hydrochloride infusion in patients with advanced T-Cell leukemia (precursor T-lymphoblastic leukemia/lymphmoma or T-cell prolymphocytic leukemia [T-PLL]) |
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E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of multiple infusion cycles of forodesine hydrochloride in this patient population. To evaluate the effect of forodesine hydrochloride on plasma levels of 2-deoxyguanosine (dGuo) and red blood cell (RBC) purine nucleoside phosphorylase (PNP) activity and to correlate levels with efficacy parameters. To describe the steady-state pharmacokinetics (PK) and pharmacodynamics (PD) of forodesine hydrochloride following repeat administration. To evaluate the maintenance of response and safety of forodesine hydrochloride in long-term treatment. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Documented T-cell leukemia (precursor T-lymphoblastic leukemia/lymphoma ot T-PLL). Failure to have responded to one or more standard regimens for their disease. Performance status of <=2 by Eastern Cooperative Oncology Group (ECOG) criteria. Age - 18 years or older. Life expectancy of at least 3 months. Adequate liver function (aspartate transaminase [AST] ond/or alanine transaminase [ALT] not > 3 times upper limits of normal. Adequate kidney function (calculated creatinine clearance >50 mL/min). Negative urine pregnancy test within 2 to 7 days prior to the start of study treatment in females of childbearing potential. Females of childbearing potential and males must be willing and able to use an adequate method of contraception to avoid pregnancy for the duration of the study. Signed informed consent/assent form prior to start of any study specific procedures. |
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E.4 | Principal exclusion criteria |
Patients with known Human Immunodeficiency Virus (HIV)infection or human T-cell leukemia virus Type 1 (HTLV-1). Patients with known Hepatitis B and/or Hepatitis C active infection. Tumor-related central nervous system (CNS) leukemia requiring active treatment. Active serious infections not controlled by oral or IV antibiotics. Treatment with any investigational antileukemic agent or chemotherapy within 7 days prior to study entry, unless full recovery from side effects has occurred. Rapidly progressive disease with compromised organ function judged to be life threatening by the investigator. Concurrent treatment with other anticancer agents (corticosteroid use will not be excluded, but patient must remain on stable dose). Pregnant and/or lactating females. Cutaneous T-cell lymphoma (CTCL) diagnosis (including Sezary syndrome) |
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of patients with a sustained response will constitute the primary outcome measure for the trial. A responsing patient is one with a partial or complete response. A patient with a sustained response is one responding to treatment for at least 28 days, beginning with the first laboratory measurement that shows a clinically significant response and concludes with the cycle-6 (or cycle-8) assessments. for precursor T-lymphoblastic leukemia/lymphoma or T-PLL patients with circulating tumor cells, a sustained response will be based on the peripheral blood assessment; for patients who have no disease in the peripheral blood, a sustained response will be based on the bone marrow assessment. For patients with extramedullary disease, a sustained response will also be based on assessments made by additional test methods (i.e. CT scans). During the 28-day period, a partial response or better status must be maintained. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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) | Yes |
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 | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |