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] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10063625 |
E.1.2 | Term | Acute lymphoblastic leukemia recurrent |
E.1.2 | System Organ Class | 100000004864 |
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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 |
Determine the antileukemic activity of combination chemotherapy including bortezomib as reinduction therapy in childhood relapsed/refractory ALL |
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E.2.2 | Secondary objectives of the trial |
- Determine the feasibility and safety of combining bortezomib with conventional combination chemotherapy in children and adolescents with relapsed/refractory ALL
- Evaluate bortezomib levels and proteasome inhibition in cerebrospinal fluid, bone marrow and peripheral blood in patients with relapsed/refractory ALL, and assess the relationship to the efficacy and toxicity of bortezomib
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age between 6 months and 19 years
- patients with a second or subsequent relapsed ALL
- patients with first relapsed ALL after prior allogeneic stem cell transplantation in first complete remission
- patients with refractory first relapse of ALL, as defined by the ALL relapse protocol these patienst were enrolled in
- circulating leukemic blasts of at least 100/ul peripheral blood (i.e. at least 0.1x109/l)
- patients must take adequate contraceptives when of childbearing potential
- written informed consent
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E.4 | Principal exclusion criteria |
- relapse not involving bone marrow
- symptomatic CNS leukemia
- Active uncontrolled infection
- Performance status (Lansky or Karnofsky score) of 60% or less
- Life expectancy of less than 6 weeks
- Existing peripheral neuropathy NCI grade 2 or higher
- Presence of acute diffuse infiltrative and/or pericardial disease
- Existing clinical signs of cardiotoxicity
- Previous allogeneic stem cell transplantation within 100 days
- Pregnant or breastfeeding
- Other contra-indications for chemotherapy, including no recovery from previous treatment
- Previous exposure to bortezomib
- other experimental or conventional antileukemic treatment within 7 days from start of bortezomib
- alergy to boron and its metabolites
- no concomitant anti-leukemic therapy other than according to this protocol
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E.5 End points |
E.5.1 | Primary end point(s) |
Antileukemic activity of bortezomib when added to dexamethasone and vincristine and intrathecal methotrexate, as determined by the absolute peripheral blood (PB) blast count on day 8 of treatment. Morphology will be centrally reviewed. |
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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. Antileukemic activity of bortezomib when added to
demathasone and vincristine and intrathecal methotrexate, as
determined by the absolute bone marrow (BM) blast percentage
on day 8, and BM and PB analysis on day 22 of treatment, in
absolute numbers and expressed as an M1, M2 or M3 marrow
(<5%, 5-15%, 15% or above respectively). Morphology will be
centrally reviewed.
2. Feasibility of combining bortezomib with dexamethasone and
vincristine and intrathecal methotrexate, as determined by the
percentage of patients in whom bortezomib had to be dosereduced
or withdrawn because of toxicity.
3. Toxicity of bortezomib when combined with dexamethasone
and vincristine and intrathecal methotrexate, as determined by
the percentage of patients suffering from grade III/IV toxicity in
any field
4. Determine the feasibility of combining a second cycle of
bortezomib with combination chemotherapy, its toxicity and
antileukemic activity, as measured after 6 weeks of therapy by
bone marrow, peripheral blood and cerebrospinal fluid. |
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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 | 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 | 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) | 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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
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 |
bortezomib early versus late administration |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |