Nilotinib With Chemotherapy for the Treatment of Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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Patients with acute lymphoblastic leukemia and positivity for the breakpoint cluster region-Abelson murine leukemia (BCR-ABL) protein or the Philadelphia chromosome have a poor prognosis with standard chemotherapy. The prognosis seemed to improve following the adition of imatinibe, a BCR-ABL inhibitor, to the treatment but still a substantial amount of patients relapse or progress during treatment. Nilotinib is a BCR-ABL inhibitor more potent than imatinib. It has been shown to be effective against most of the cells that bear mutations of the BCR-ABL protein leading to resistance to imatinibe. The investigators' hypothesis is that the addition of nilotinib to a standard chemotherapy for acute lymphoblastic leukemia (ALL) will translate into more rapid BCR-ABL reduction and effectiveness against imatinib-resistant clones leading to less relapses and better survival.

Official Title
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Estudo da eficácia do Nilotinibe Concomitante à Quimioterapia no Tratamento de Pacientes Com Leucemia linfoblástica Aguda Filadélfia Positiva recém-diagnosticada

Conditions
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Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: Nilotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Acute Lymphoblastic Leukemia (ALL) BCR-ABL positive positive by PCR (central Lab) No previous treatment for ALL except for corticoids and cyclophosphamide less than 600 mg/m2 Must be able to swallow tablets Lab results within normal limits (Potassium, Calcium, Magnesio, Phosphorus, Transaminases, Alkaline Phosphatase, Bilirrubine, Amylase, Lypase) Exclusion Criteria: Heart disease Interval QTc Fridericia > 480 msec Coumadin use Pregnancy PS = 4 Previous medical history of etilism or/and pancreatic disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: nilotinib<br>single arm study | Drug: Nilotinib<br>* 400mg, Oral, Bid, Daily for three years<br>* Other names: AMN107;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission |  | Day + 21 and Day + 41 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | Three years | 
| Molecular remission |  | Every three months until three years | 
| Toxicity |  | Three times a week for the first 40 days than once weekly for the next 9 months than monthly for the next 2.1 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Leukemia, Lymphoblastic, Acute, Philadelphia, BCR-ABL, Nilotinib, Treatment