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 | 10024338 |
E.1.2 | Term | Leukemia lymphoblastic acute |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 feasibility of patient accrual and toxicity of an intensified chemotherapeutic regimen incorporating novel agents for treatment of children and adolescents with VHR ALL. |
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E.2.2 | Secondary objectives of the trial |
1. To determine if the BCR-ABL-specific tyrosine kinase inhibitor STI571 can be incorporated into this regimen with acceptable toxicity for patients with Ph+ ALL
2. To compare EFS for VHR patients treated with the intensive chemotherapy with that of historical controls
3. To conduct a preliminary evaluation of the feasibility and efficacy of following intensive reinduction by Hematopoietic Stem Cell Transplantation (HSCT) as therapy for patients with an HLA-matched related donors
4. To determine if MRD assessed at the end of induction and prior to intensification therapy by PCR and flow cytometry can predict relapse
5. To evaluate whether MRD detected by PCR at post-intensification time points is prognostically significant |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients 1 to 20 years of age diagnosed with ALL who achieve remission after frontline induction therapy must have one of the features listed below:
a. Ph+ ALL: presence of t(9;22)(q34;q11) determined by institutional cytogenetics or FISH; and/or presence of BCR-ABL fusion transcript identified by RT-PCR
b. Hypodiploid with ≤ 44 chromosomes
2. Patients 1 to 20 years of age diagnosed with ALL who do not achieve remission after frontline induction therapy must have one of the features listed below:
a. M3 (> 25% blasts) bone marrow status at the end of initial induction therapy
b. M2 (5-25% blasts) bone marrow status at the end of initial induction therapy and M2 or M3 bone marrow status at end of consolidation therapy (CCG studies) or at the end of the extended induction phase (POG studies).
3. Patients who are Ph+, hypodiploid with ≤ 44 chromosomes, or M3 at the end of induction therapy must enroll on study within 42 days of initial diagnosis.
4. Patients who are M2 at the end of induction and M2 or M3 at the end of consolidation therapy (CCG) or extended induction therapy (POG) must enroll within 14 days of their last day of frontline therapy |
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E.4 | Principal exclusion criteria | |
E.5 End points |
E.5.1 | Primary end point(s) |
•Feasibility, in terms of toxicity and patient accrual
•Safety |
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E.5.2 | Secondary end point(s) |
•Event-free survival
•Feasibility of administering hematopoietic stem cell transplantation after the second consolidation block of chemotherapy
•Prognostic effect of minimal residual disease assays |
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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 | 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) | Yes |
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.8.3 |
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 |
Australia |
Canada |
New Zealand |
United States |
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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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 2 |