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

Sponsor

Japan Adult Leukemia Study Group (Other)

Overall Status

Unknown status

CT.gov ID

NCT00131027

Collaborator

(none)

240

Enrollment

Location

Arms

108

Duration (Months)

2.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoblastic Leukemia, Acute	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	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

240 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Sep 1, 2002

Anticipated Primary Completion Date :

Mar 1, 2011

Anticipated Study Completion Date :

Sep 1, 2011

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: A

HD-MTX

Drug: Cyclophosphamide

Drug: Daunorubicin

Drug: Vincristine

Drug: Prednisolone

Drug: L-asparaginase

Drug: Cytarabine

Drug: Etoposide

Drug: Dexamethasone

Drug: Methotrexate

3 g/sqm (high dose)

Drug: Mercaptopurine

Drug: Doxorubicin

Active Comparator: B

ID-MTX

Drug: Cyclophosphamide

Drug: Daunorubicin

Drug: Vincristine

Drug: Prednisolone

Drug: L-asparaginase

Drug: Cytarabine

Drug: Etoposide

Drug: Dexamethasone

Drug: Mercaptopurine

Drug: Doxorubicin

Drug: Methotrexate

0.5 g/sqm (intermediate dose)

Outcome Measures

Primary Outcome Measures

Disease-free survival [3 years]

Secondary Outcome Measures

Toxicity [2 years]
The rate of complete remission [2 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 64 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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