German Multicenter Trial for Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Adults (07/2003)

Sponsor

Goethe University (Other)

Overall Status

Completed

CT.gov ID

NCT00198991

Collaborator

Deutsche Krebshilfe e.V., Bonn (Germany) (Other), German Federal Ministry of Education and Research (Other)

1,883

Enrollment

Location

Arm

123

Actual Duration (Months)

15.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study evaluates the efficacy and tolerability of an intensified induction and consolidation therapy. Thereafter patients receive individualised treatment stratified according to relapse risk with stem cell transplantation for patients with high and very high risk of relapse. Patients with standard risk receive further consolidation and reinduction chemotherapy. In parallel minimal residual disease (MRD) is evaluated. After six months and one year the decision on intensification or discontinuation of therapy is made based on the results of MRD evaluation.

Condition or Disease	Intervention/Treatment	Phase
Adult Acute Lymphocytic Leukemia	Drug: Cyclophosphamide Drug: Dexamethasone Drug: Vincristine Drug: Daunorubicin Drug: Asparaginase Drug: Methotrexate Drug: Cytarabine Drug: Mercaptopurine Drug: G-CSF Drug: Vindesine Drug: Etoposide Drug: Prednisolone Drug: Adriamycin Drug: Thioguanine Drug: Teniposide Procedure: CNS irradiation Procedure: Mediastinal Irradiation Procedure: Stem cell transplantation (SCT) Drug: Idarubicin Drug: Fludarabine Drug: Cladribine	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

1883 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

German Multicenter Study for Treatment Optimisation in Acute Lymphoblastic Leukemia in Adults and Adolescents Above 15 Years (Amend 3) (GMALL 07/2003)

Actual Study Start Date :

Apr 1, 2003

Actual Primary Completion Date :

Jun 30, 2011

Actual Study Completion Date :

Jun 30, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: All patients All patients are treated upfront according to one arm	Drug: Cyclophosphamide Cytostatic drug Drug: Dexamethasone Antileukemic drug Drug: Vincristine Cytostatic drug Drug: Daunorubicin Cytostatic drug Drug: Asparaginase Cytostatic drug Other Names: Pegylated Asparaginase Drug: Methotrexate Cytostatic drug Drug: Cytarabine Cytostatic drug Drug: Mercaptopurine Cytostatic drug Drug: G-CSF Growth factor Drug: Vindesine Cytostatic drug Drug: Etoposide Cytostatic drug Other Names: Etoposide Phosphate Drug: Prednisolone Antileukemic drug Drug: Adriamycin Cytostatic drug Drug: Thioguanine Cytostatic drug Drug: Teniposide Cytostatic drug Procedure: CNS irradiation Cytostatic drug Procedure: Mediastinal Irradiation Irradiation Procedure: Stem cell transplantation (SCT) Stem cell transplantation Drug: Idarubicin Cytostatic drug Drug: Fludarabine Cytostatic drug Drug: Cladribine Cytostatic drug

Arm

Intervention/Treatment

Experimental: All patients

All patients are treated upfront according to one arm

Drug: Cyclophosphamide

Cytostatic drug

Drug: Dexamethasone

Antileukemic drug

Drug: Vincristine

Cytostatic drug

Drug: Daunorubicin

Cytostatic drug

Drug: Asparaginase

Cytostatic drug

Other Names:

Pegylated Asparaginase

Drug: Methotrexate

Cytostatic drug

Drug: Cytarabine

Cytostatic drug

Drug: Mercaptopurine

Cytostatic drug

Drug: G-CSF

Growth factor

Drug: Vindesine

Cytostatic drug

Drug: Etoposide

Cytostatic drug

Other Names:

Etoposide Phosphate

Drug: Prednisolone

Antileukemic drug

Drug: Adriamycin

Cytostatic drug

Drug: Thioguanine

Cytostatic drug

Drug: Teniposide

Cytostatic drug

Procedure: CNS irradiation

Cytostatic drug

Procedure: Mediastinal Irradiation

Irradiation

Procedure: Stem cell transplantation (SCT)

Stem cell transplantation

Drug: Idarubicin

Cytostatic drug

Drug: Fludarabine

Cytostatic drug

Drug: Cladribine

Cytostatic drug

Outcome Measures

Primary Outcome Measures

Remission rate [day 46]
Rate of patients with complete remission
Remission duration [up to 10 years]
Rate and probability of patients with ongoing remission after prior achievement of remission
Disease free survival [up to 10 years]
Rate and probability of patients remaining disease free i.e without relapse, death in CR or secondary malignancy
Overall survival [up to 10 years]
Rate and probability of patients remaining alive

Secondary Outcome Measures

Realisation of Stem cell transplantation (SCT) [up to 10 years]
Rate of patients receiving an SCT
Toxicity according to WHO/CTCAE [after each cycle up to 2.5 years]
Rate of adverse events according to WHO/CTCAE (cycle duration in this complex protocol is variable and cannot be specified)
Response assessment based on MRD [up to 5 years]
Rate of MRD response after specific cycles

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Acute lymphoblastic leukemia (pro-B, common, pre-B, early T, thymic T, mature T)
Age 15-65 yrs (*55-65 years if biologically younger according to general condition)
Written informed consent

Exclusion Criteria:

Severe comorbidity or leukemia associated complications
Late relapse of pediatric ALL or ALL as second malignancy
Cytostatic pre-treatment
Pregnancy
Severe psychiatric illness or other circumstances which may compromise cooperation of the patient
Participation in other clinical trials interfering with the study therapy