Study of Imatinib-Combined Chemotherapy for BCR-ABL-Positive Acute Lymphoblastic Leukemia (ALL)

Study Overview
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Brief Summary
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The purpose of this study is to determine the clinical efficacy and safety of imatinib-combined chemotherapy on newly diagnosed BCR-ABL-positive ALL.

Detailed Description
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Philadelphia chromosome (Ph) is a translocation abnormality leading to the formation of the BCR-ABL gene rearrangement. This genetic abnormality occurs in up to 30% of adult acute lymphoblastic leukemia (ALL), and its presence is known to be the most adverse prognostic factor for ALL. Because long-term survival cannot be achieved by conventional chemotherapy alone, there is a clear medical need for alternative treatment approaches. Imatinib is a potent selective inhibitor of the BCR-ABL protein kinase, and it has been reported that single-agent imatinib induced response in a substantial proportion of Ph-positive ALL (Ph+ALL) patients, but that the response was not durable. The Japan Adult Leukemia Study Group (JALSG) has therefore started a phase 2 study designed to evaluate the clinical effect of imatinib-combined chemotherapy on newly diagnosed BCR-ABL-positive ALL.

Official Title
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Phase 2 Study of Imatinib-Combined Chemotherapy for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia

Conditions
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Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: imatinib
* Drug: cyclophosphamide
* Drug: daunorubicin
* Drug: vincristine
* Drug: prednisolone
* Drug: methotrexate
* Drug: cytarabine
* Drug: dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously untreated BCR-ABL-positive ALL Age between 15 and 64 years Performance status between 0 and 3 (ECOG criteria) Adequate functioning of the liver (serum bilirubin level < 2.0 mg/dL), kidneys (serum creatinine level < 2.0 mg/dL), and heart (left ventricular ejection fraction greater than 50% and no severe abnormalities detected on electrocardiograms and echocardiographs) Written informed consent to participate in the trial Exclusion Criteria: Uncontrolled active infection Another severe and/or life-threatening disease Positive for HIV antibody and/or hepatitis B surface (HBs) antigen tests Another primary malignancy which is clinically active and/or requires medical interventions Pregnant and/or lactating women Past history of renal failure

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 64 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: A<br> | Drug: imatinib<br> <br> Drug: cyclophosphamide<br> <br> Drug: daunorubicin<br> <br> Drug: vincristine<br> <br> Drug: prednisolone<br> <br> Drug: methotrexate<br> <br> Drug: cytarabine<br> <br> Drug: dexamethasone<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of complete remission |  | 63 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The duration of remission |  | 1 year | 
| Overall survival |  | 1 year | 
| Toxicity caused by combination of imatinib and chemotherapy |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute lymphoblastic leukemia, BCR-ABL, Philadelphia-chromosome, newly diagnosed