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

NCT00198991 | Completed Phase 4

• 1 other identifier: GMALL01
• Study Type: interventional
• Target: 1,883
• Locations: 1 country
• Sites: 1

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.

Conditions

Adult Acute Lymphocytic Leukemia

Keywords

ALL; Treatment; de novo; Minimal residual disease; Adult

Outcome Measures

Primary Outcomes (4)

• Remission rate

  Rate of patients with complete remission

  day 46

• Remission duration

  Rate and probability of patients with ongoing remission after prior achievement of remission

  up to 10 years

• Disease free survival

  Rate and probability of patients remaining disease free i.e without relapse, death in CR or secondary malignancy

  up to 10 years

• Overall survival

  Rate and probability of patients remaining alive

  up to 10 years

Secondary Outcomes (3)

• Realisation of Stem cell transplantation (SCT)

  up to 10 years

• Toxicity according to WHO/CTCAE

  after each cycle up to 2.5 years

• Response assessment based on MRD

  up to 5 years

Study Arms (1)

All patients

EXPERIMENTAL

All patients are treated upfront according to one arm

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

Interventions

Cyclophosphamide DRUG

Cytostatic drug

All patients

Dexamethasone DRUG

Antileukemic drug

All patients

Vincristine DRUG

Cytostatic drug

All patients

Daunorubicin DRUG

Cytostatic drug

All patients

Asparaginase DRUG

Cytostatic drug

Also known as: Pegylated Asparaginase

All patients

Methotrexate DRUG

Cytostatic drug

All patients

Cytarabine DRUG

Cytostatic drug

All patients

Mercaptopurine DRUG

Cytostatic drug

All patients

G-CSF DRUG

Growth factor

All patients

Vindesine DRUG

Cytostatic drug

All patients

Etoposide DRUG

Cytostatic drug

Also known as: Etoposide Phosphate

All patients

Prednisolone DRUG

Antileukemic drug

All patients

Adriamycin DRUG

Cytostatic drug

All patients

Thioguanine DRUG

Cytostatic drug

All patients

Teniposide DRUG

Cytostatic drug

All patients

CNS irradiation PROCEDURE

Cytostatic drug

All patients

Mediastinal Irradiation PROCEDURE

Irradiation

All patients

Stem cell transplantation (SCT) PROCEDURE

Stem cell transplantation

All patients

Idarubicin DRUG

Cytostatic drug

All patients

Fludarabine DRUG

Cytostatic drug

All patients

Cladribine DRUG

Cytostatic drug

All patients

Eligibility Criteria

• Age: 15 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Goethe University: lead
• Deutsche Krebshilfe e.V., Bonn (Germany): collaborator
• German Federal Ministry of Education and Research: collaborator

Study Sites (1)

University of Frankfurt, Medical Dept. II

Frankfurt, 60590, Germany

Location

Related Publications (6)

• Kobitzsch B, Gokbuget N, Schwartz S, Reinhardt R, Bruggemann M, Viardot A, Wasch R, Starck M, Thiel E, Hoelzer D, Burmeister T. Loss-of-function but not dominant-negative intragenic IKZF1 deletions are associated with an adverse prognosis in adult BCR-ABL-negative acute lymphoblastic leukemia. Haematologica. 2017 Oct;102(10):1739-1747. doi: 10.3324/haematol.2016.161273. Epub 2017 Jul 27.

  PMID: 28751559 DERIVED

• Herold T, Schneider S, Metzeler KH, Neumann M, Hartmann L, Roberts KG, Konstandin NP, Greif PA, Braundl K, Ksienzyk B, Huk N, Schneider I, Zellmeier E, Jurinovic V, Mansmann U, Hiddemann W, Mullighan CG, Bohlander SK, Spiekermann K, Hoelzer D, Bruggemann M, Baldus CD, Dreyling M, Gokbuget N. Adults with Philadelphia chromosome-like acute lymphoblastic leukemia frequently have IGH-CRLF2 and JAK2 mutations, persistence of minimal residual disease and poor prognosis. Haematologica. 2017 Jan;102(1):130-138. doi: 10.3324/haematol.2015.136366. Epub 2016 Aug 25.

  PMID: 27561722 DERIVED

• Topp MS, Gokbuget N, Zugmaier G, Degenhard E, Goebeler ME, Klinger M, Neumann SA, Horst HA, Raff T, Viardot A, Stelljes M, Schaich M, Kohne-Volland R, Bruggemann M, Ottmann OG, Burmeister T, Baeuerle PA, Nagorsen D, Schmidt M, Einsele H, Riethmuller G, Kneba M, Hoelzer D, Kufer P, Bargou RC. Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL. Blood. 2012 Dec 20;120(26):5185-7. doi: 10.1182/blood-2012-07-441030. Epub 2012 Sep 28.

  PMID: 23024237 DERIVED

• Gokbuget N, Stanze D, Beck J, Diedrich H, Horst HA, Huttmann A, Kobbe G, Kreuzer KA, Leimer L, Reichle A, Schaich M, Schwartz S, Serve H, Starck M, Stelljes M, Stuhlmann R, Viardot A, Wendelin K, Freund M, Hoelzer D; German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia. Outcome of relapsed adult lymphoblastic leukemia depends on response to salvage chemotherapy, prognostic factors, and performance of stem cell transplantation. Blood. 2012 Sep 6;120(10):2032-41. doi: 10.1182/blood-2011-12-399287. Epub 2012 Apr 4.

  PMID: 22493293 DERIVED

• Gokbuget N, Kneba M, Raff T, Trautmann H, Bartram CR, Arnold R, Fietkau R, Freund M, Ganser A, Ludwig WD, Maschmeyer G, Rieder H, Schwartz S, Serve H, Thiel E, Bruggemann M, Hoelzer D; German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia. Adult patients with acute lymphoblastic leukemia and molecular failure display a poor prognosis and are candidates for stem cell transplantation and targeted therapies. Blood. 2012 Aug 30;120(9):1868-76. doi: 10.1182/blood-2011-09-377713. Epub 2012 Mar 22.

  PMID: 22442346 DERIVED

• Burmeister T, Meyer C, Schwartz S, Hofmann J, Molkentin M, Kowarz E, Schneider B, Raff T, Reinhardt R, Gokbuget N, Hoelzer D, Thiel E, Marschalek R. The MLL recombinome of adult CD10-negative B-cell precursor acute lymphoblastic leukemia: results from the GMALL study group. Blood. 2009 Apr 23;113(17):4011-5. doi: 10.1182/blood-2008-10-183483. Epub 2009 Jan 14.

  PMID: 19144982 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Neoplasm, Residual

Interventions

Cyclophosphamide; Dexamethasone; Vincristine; Daunorubicin; Asparaginase; pegaspargase; Methotrexate; Cytarabine; Mercaptopurine; Granulocyte Colony-Stimulating Factor; Vindesine; Etoposide; etoposide phosphate; Prednisolone; Doxorubicin; Thioguanine; Teniposide; Stem Cell Transplantation; Idarubicin; fludarabine; Cladribine

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Aminoglycosides; Glycosides; Carbohydrates; Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Aminopterin; Pterins; Pteridines; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Sulfhydryl Compounds; Sulfur Compounds; Purines; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; 2-Chloroadenosine; Adenosine; Purine Nucleosides; Deoxyadenosines; Deoxyribonucleosides; Ribonucleosides

Study Officials

• Dieter Hoelzer, MD,PhD

  University Hospital of Frankfurt, Medical Dept. II

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 20, 2005
• Study Start: April 1, 2003
• Primary Completion: June 30, 2011
• Study Completion: June 30, 2013
• Last Updated: August 18, 2022

Record last verified: 2022-08

Locations

DE (1)