| DEC-NET Serial number GB342 |
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| Published online | 18/01/2005 10.41.00 |
| Last updated | 19/07/2005 10.39.53 |
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| This trial has been approved by an ethics committee |
| Current trial status | Open (actively recruiting new participants) |
First subject enrolment
Target N. of subjects |
07/2004
36 |
Major Disease
(ICD9 class) | LYMPHOID LEUKEMIA ACUTE |
| Experimental drug |
IMATINIB
Treatment regimen (dosage and duration)
300mg/m2 Initially for 28 days then 14 day block |
IFOSFAMIDE
Treatment regimen (dosage and duration)
800mg/M2 from end of methotrexate infusion |
METHOTREXATE
Treatment regimen (dosage and duration)
20mg/m2 once weekly during interim maintenance |
CYCLOPHOSPHAMIDE
Treatment regimen (dosage and duration)
200mg/m2 on days 2-4 of consolidation block 1 and on day 36 of delayed intensification Phase IIB and second delayed reintensification Phase IIB |
DEXAMETHASONE
Treatment regimen (dosage and duration)
10mg/m2 days 1-21 of delayed (and second) reintensification, days 1-5 of consolidation block 1, 2 and 3, and days 1-5 continuation therapy |
DAUNORUBICIN
Treatment regimen (dosage and duration)
30mg/m2 day 5 consolidation block 2. |
ETOPOSIDE
Treatment regimen (dosage and duration)
100mg/m2 for 5 doses on days 3-5 of consolidation block 3 |
DOXORUBICIN HYDROCHLORIDE
Treatment regimen (dosage and duration)
25mg/m2 on day 8, day 15, day 22, day 29 of delayed reintensification. |
MERCAPTOPURINE
Treatment regimen (dosage and duration)
60mg/m2 days 1-28 of Phase IB, 50mg/m2 days 1-29 of maintenance |
| Gender | Both |
| Age (range) | <18 |
Eligibility criteria |
| Inclusion criteria |
| Children and adolescents aged under 18 years at diagnosis, with Ph+ALL documented by FISH for BCR-ABL, who are eligible for the current local prospective therapeutic study of childhood ALL and for whom informed consent was given by the parents or by legal guardian or young adult |
| Exclusion criteria |
| On day 36 at the start of the first course of IMATINIB
1. Abnormal hepatic function (ALT/AST > 10 times the upper limit of the normal range);
2. Abnormal renal function (creatinine > 1.5 times the upper limit of the normal range or a calculated creatinine clearance of 80ml/ min or less, adjusted to a body surface area of 1.73 sqm);
3. Active systemic bacterial, fungal or viral infection as documented by positive cultures, radiological imaging techniques, and septic shock symptoms.
4. Are pregnant or lactating. Male and female patients who are fertile must agree to use an effective means of birth control (i.e., latex condom, diaphragm, cervical cap, etc) to avoid pregnancy.
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Trial design/methodology |
| Phase | 2 |
| Kind of study | Efficacy
Safety
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| Design | Controlled
Randomised
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| Purpose of study |
| The primary objective is to utilise a new chemotherapy approach for children with relapsed acute lymphoblastic leukaemia (ALL) based on risk group stratification and therapy directed by the presence of minimal residual disease. The aim is to standardise nationally the treatment of children with ALL who fail induction or relapse once morpholigical remission has been obtained. |
| Primary outcomes |
| The following end points will be used , stratified by risk group: death in continuous clinical remission, relapse, second malignancy. The MRD level of 10-4, will be used at the end of induction in the intermediate group to distinguish those who will benefit from chemotherapy or BMT. |
| Secondary outcomes |
| Feasibility and safety of the addition of IMATINIB to conventional chemotherapy schedule.
2. Long term clinical outcome (EFS, survival)
3. Pattern of molecular response at the 5 scheduled time points for MRD measurement.
4. Conversion rate to CR in patients resistant to the first part of the induction phase of chemotherapy included in the Poor-risk group.
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| Summary of study design, objectives, and ongoing research findings |
| This is an international, intergroup, multicentre, open label, randomised, Phase II/III clinical trial. The study aims to evaluate the efficacy of Imatinib when added to post induction therapy in children with Philadelphia-positive (Ph+) acute lymphoblastic leukaemia (ALL). The end point being sought is event (EFS) and disease free survival (DFS). Secondary objectives include evaluating the safety of Imatinib use with combination chemotherapy, the pattern of molecular response to therapy and the use of minimal residual disease as a surrogate marker for response to treatment. Ph+ ALL is a subset of childhood ALL with a poor outcome with chemotherapy and children with this type of disease are usually transplanted. Even with this approach the EFS is considerably lower than that of standard risk ALL. This study wishes to evaluate the use of Imatinib in addition to standard combination chemotherapy to treat children with Ph+ ALL. The hypothesis is that, Imatinib by inhibiting ABL tyrosine kinase may make the cells more susceptible to chemotherapy and the use of the latter will prevent the emergence of Imatinib resistance.
All children will be induced according to ALL2003 guidelines. Once Ph+ has been confirmed by FISH, the Trial Manager will be informed and Novartis. All children who give written informed consent will receive post-induction treatment according to EsPhALL. Children who have a good marrow response are eligible for randomisation to receive or not receive Imatinib (GlivecÒ) along with the post-induction treatment. Those who refuse to be randomised should be treated according to Regimen C of ALL2003. All children with poor risk disease will receive Imatinib along with chemotherapy. All children are eligible for allogeneic stem cell transplantation at the end of the block HR3.
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