Phase II Study for Safety and Efficacy Evaluation of Imatinib Mesylate in Children With Chronic Myeloid Leukemia (CML) Philadelphia Chromosome-positive (Ph+)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the hematological, cytogenetic and molecular response to continuous-use of Imatinib in children with CML Ph+.

Official Title
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Phase II Study for Safety and Efficacy Evaluation of Imatinib Mesylate in Children With Chronic Myeloid Leukemia (CML) Philadelphia Chromosome-positive (Ph+)

Conditions
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Chronic Myeloid Leukemia (CML) With Philadelphia Chromosome-positive (Ph+)

Intervention / Treatment
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* Drug: Imatinib Mesylate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnose: suspected CML (hematology and/or myelogram and/or immunophenotyping and/or Leukocyte alkaline phosphatase [LAP]) to be confirmed, after, by cytogenetic and/or molecular biology. OBS: only CML Ph+ newly-diagnose in chronic or accelerate phase; resistant CML Ph+ to Interferon α (INF-α), Hydroxyurea and/or low-dose ARA-C in chronic or accelerate phase; CML Ph+ with cytogenetic relapse after BMT, that didn't use Imatinib previously, in chronic or accelerate phase. Female patients of childbearing age, should have pregnancy test (blood βhCG) performed before treatment initiation. Effective contraception must be used. Pregnant women won't be included. Karnofsky and Lansky scale: ≥40. Life expectation > 8 weeks. Laboratory: renal function (serum creatinine ≤ 1,5 x ULN and/or Clearance ≥70 ml/min/1,73m2), hepatic function (total bilirubin ≤ 1,5 x ULN, TGP < 3 x ULN and albumin > 2 g/dl. CNS toxicity ≤ II Cardiac function: normal ejection fraction. Signed ICF by child legal responsible. Exclusion Criteria: Patient receiving any other tyrosine kinase inhibitor (TKI). Pregnant patient or breastfeeding. Patient considered incapable to follow purposed treatment. Patients with molecular relapsed. Medications: Colony stimulating: it cannot be administered at least 1 week before treatment. Anticonvulsants: Imatinib is metabolized by P-450 enzyme, thereby subject cannot receive drug that activates the P-450 system. The anticonvulsants allowed are valproic acid and benzodiazepines. Anticoagulants: The use of warfarin (Marevan) is not allowed. If anticoagulant is needed, low-molecular-weight heparin (LMWH) can be used. Avoid anticoagulants with platelets < 50000. INF-Α 48h before D1. Hydroxyurea 24h before D1. ARA-C doses >100 mg/m2 for 5-7 days, 14 days before D1. Anthracyclines, Mitoxantrone or Etoposide 21 days before D1. Any other chemotherapeutic agent 28 days before D1. Hematopoietic Cell Transplantation (HCT) 6 weeks before D1.

Ages Eligible for Study
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Maximum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Imatinib Mesylate<br> | Drug: Imatinib Mesylate<br>* Patient will receive Imatinib Mesylate, continuous-use, 260 mg/m2/day dose, maximum allowed 400 mg, for 24 months.<br>* Other names: Glivec, MI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the complete cytogenetic response with continuous-use of Imatinib. |  | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the response to continuous-use of Imatinib and the toxicity and tolerability in children with CML Ph+. |  | Up to 24 months |