High-Dose Methotrexate (MTX) for Adult Acute Lymphoblastic Leukemia (ALL)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate the clinical efficacy of high-dose methotrexate consolidation therapy for adult patients with BCR-ABL-negative ALL.

Detailed Description
-----------------
Although the multi-agent chemotherapies in current use produce complete remission for a majority of patients with acute lymphoblastic leukemia (ALL), the prognosis for adult ALL remains discouraging due to a high incidence of relapse. Optimal post-remission therapy, therefore, has been a matter of vital concern. In some pediatric ALL studies, the use of high-dose methotrexate (MTX) as a consolidation therapy, has been shown to improve outcome, however, there has been no randomized controlled trials to test its clinical efficacy in adult ALL. With this concern, the Japan Adult Leukemia Study Group (JALSG) has planned a prospective randomized controlled trial comparing high-dose MTX and intermediate-dose MTX for ALL patients who are negative for BCR-ABL. Those who are positive for BCR-ABL can participate in a separate protocol.

Official Title
-----------------
Randomized Controlled Trial to Test Efficacy of High-Dose Methotrexate Consolidation Therapy for BCR-ABL-Negative Acute Lymphoblastic Leukemia in Adults

Conditions
-----------------
Lymphoblastic Leukemia, Acute

Intervention / Treatment
-----------------
* Drug: Cyclophosphamide
* Drug: Daunorubicin
* Drug: Vincristine
* Drug: Prednisolone
* Drug: L-asparaginase
* Drug: Cytarabine
* Drug: Etoposide
* Drug: Dexamethasone
* Drug: Methotrexate
* Drug: Mercaptopurine
* Drug: Doxorubicin
* Drug: Methotrexate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Previously untreated BCR-ABL-negative ALL Age between 25 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
-----------------
Minimum Age: 25 Years
Maximum Age: 64 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>HD-MTX | Drug: Cyclophosphamide<br> <br> Drug: Daunorubicin<br> <br> Drug: Vincristine<br> <br> Drug: Prednisolone<br> <br> Drug: L-asparaginase<br> <br> Drug: Cytarabine<br> <br> Drug: Etoposide<br> <br> Drug: Dexamethasone<br> <br> Drug: Methotrexate<br>* 3 g/sqm (high dose)<br>Drug: Mercaptopurine<br> <br> Drug: Doxorubicin<br> <br> |
| Active Comparator: B<br>ID-MTX | Drug: Cyclophosphamide<br> <br> Drug: Daunorubicin<br> <br> Drug: Vincristine<br> <br> Drug: Prednisolone<br> <br> Drug: L-asparaginase<br> <br> Drug: Cytarabine<br> <br> Drug: Etoposide<br> <br> Drug: Dexamethasone<br> <br> Drug: Mercaptopurine<br> <br> Drug: Doxorubicin<br> <br> Drug: Methotrexate<br>* 0.5 g/sqm (intermediate dose)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity |  | 2 years | 
| The rate of complete remission |  | 2 months | 

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