Optimization of Therapy in Adult Patients With Newly Diagnosed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma by Individualised, Targeted and Intensified Treatment

NCT02881086 | Completed Phase 3 DMC

• 1 other identifier: GMALL08_2013
• Study Type: interventional
• Target: 1,023
• Locations: 1 country
• Sites: 1

Brief Summary

A phase IV study with the primary goal to optimize therapy of adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma (LBL) by dose and time intensive, pediatric based chemotherapy, risk adapted stem cell transplantation (SCT) and minimal residual disease (MRD) based individualised and intensified therapy. Study will further evaluate the role of asparaginase intensification, the extended use of rituximab and the use of nelarabine as consolidation therapy in T-ALL in a phase III-part of the study. Furthermore two randomisations will focus on the role of central nervous system (CNS) irradiation in combination with intrathecal therapy versus intrathecal therapy only in B-precursor ALL/LBL and the role of SCT in high-risk patients with molecular complete remission. Finally a new, dose reduced induction therapy in combination with Imatinib will be evaluated in Ph/BCR-ABL positive ALL.

Conditions

Lymphoblastic Lymphoma; Acute Lymphoblastic Leukemia

Keywords

Acute lymphoblastic leukemia; Lymphoblastic lymphoma; Nelarabine; BCR-ABL; MRD; PEG-Asparaginase; Rituximab

Outcome Measures

Primary Outcomes (1)

• Event free survival

  3.5 years

Secondary Outcomes (2)

• Time until consolidation treatment I

  approximately 70 days

• Disease free survival

  1 year

Other Outcomes (14)

• Hematological remission rate

  after induction, approximately 6-8 weeks from diagnosis

• Molecular remission rate

  after induction and consolidation, approximately 6-8 weeks from diagnosis

• Results of the positron emission tomography (PET) based remission evaluation

  after consolidation, approximately 8-10 weeks

Study Arms (9)

Stratification I - Standard Risk (SR)/ High Risk (HR)

OTHER

Induction and consolidation I therapy for standard and high risk patients, PH/BCR-ABL-negative Chemotherapy, immunotherapy, intrathecal prophylaxis, CNS irradiation according to randomisation I Drugs: Rituximab, Vincristine, Daunorubicin, Dexamethasone, Cyclophosphamide, Cytarabine, Mercaptopurine, PEG-Asparaginase, Methotrexate, Vindesine, VP16

Drug: Rituximab; Drug: PEG-Asparaginase; Drug: Dexamethasone; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Mercaptopurine; Drug: VP16; Drug: Daunorubicin (DNR); Drug: Methotrexate; Drug: Cytarabine; Drug: Vindesine

Stratification I - Philadelphia (PH)+

OTHER

Induction and consolidation I therapy for PH+ patients Chemotherapy, immunotherapy, intrathecal prophylaxis Drugs: Rituximab, Vincristine, Imatinib, Dexamethasone, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, VP16

Drug: Rituximab; Drug: PEG-Asparaginase; Drug: Imatinib; Drug: Dexamethasone; Drug: Vincristine; Drug: VP16; Drug: Methotrexate; Drug: Cytarabine; Drug: Vindesine

Rand I - B-Lin + CNS Rad + i.th. MTX

ACTIVE COMPARATOR

Chemotherapy according to Stratification I SR/HR CNS prophylaxis: CNS irradiation 24 Gy, intrathecal Methotrexate

Procedure: Cranial irradiation; Drug: Methotrexate

Rand I - B-Lin + i.th. MTX

EXPERIMENTAL

Chemotherapy according to Stratification I SR/HR CNS prophylaxis: intrathecal Methotrexate

Drug: Methotrexate

Stratification II - SR + MRD-neg

OTHER

Chemotherapy, immunotherapy, intrathecal prophylaxis, consolidation II, reinduction, consolidation III - VI, maintenance Drugs: Rituximab, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, Adriamycin, Prednisolone, Cyclophosphamide, Nelarabine, Dexamethasone

Drug: Rituximab; Drug: Nelarabine; Drug: PEG-Asparaginase; Drug: Dexamethasone; Drug: Cyclophosphamide; Drug: Methotrexate; Drug: Cytarabine; Drug: Vindesine; Drug: Adriamycin; Drug: Prednisolone

Stratification II - HR + MRD-neg

OTHER

Chemotherapy or stem cell transplantation according to randomisation II

Drug: Rituximab; Drug: Nelarabine; Drug: PEG-Asparaginase; Drug: Cyclophosphamide; Drug: Methotrexate; Procedure: Stem cell transplantation; Drug: Cytarabine; Drug: Vindesine; Drug: Adriamycin; Drug: Prednisolone

Stratification II - SR/HR/PH+ + MRD-pos

OTHER

Chemotherapy or targeted therapy, followed by stem cell transplantation Drugs: Fludarabine, Idarubicin, Cytarabine, Nelarabine

Drug: Nelarabine; Drug: Idarubicin; Drug: Fludarabine; Drug: Cytarabine

Randomisation II - HR + MRD-neg-SCT

ACTIVE COMPARATOR

Stem cell transplantation

Procedure: Stem cell transplantation

Randomisation II - HR + MRD-neg-SR-chemo

EXPERIMENTAL

Chemotherapy, immunotherapy, intrathecal prophylaxis, consolidation II, reinduction, consolidation III - VI, maintenance Drugs: Rituximab, Dexamethasone, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, Adriamycin, Prednisolone, Cyclophosphamide, Nelarabine

Drug: Rituximab; Drug: Nelarabine; Drug: PEG-Asparaginase; Drug: Dexamethasone; Drug: Cyclophosphamide; Drug: Methotrexate; Drug: Cytarabine; Drug: Vindesine; Drug: Adriamycin; Drug: Prednisolone

Interventions

Rituximab DRUG

Randomisation II - HR + MRD-neg-SR-chemo; Stratification I - Philadelphia (PH)+; Stratification I - Standard Risk (SR)/ High Risk (HR); Stratification II - HR + MRD-neg; Stratification II - SR + MRD-neg

Nelarabine DRUG

Randomisation II - HR + MRD-neg-SR-chemo; Stratification II - HR + MRD-neg; Stratification II - SR + MRD-neg; Stratification II - SR/HR/PH+ + MRD-pos

PEG-Asparaginase DRUG

Randomisation II - HR + MRD-neg-SR-chemo; Stratification I - Philadelphia (PH)+; Stratification I - Standard Risk (SR)/ High Risk (HR); Stratification II - HR + MRD-neg; Stratification II - SR + MRD-neg

Cranial irradiation PROCEDURE

Rand I - B-Lin + CNS Rad + i.th. MTX

Imatinib DRUG

Stratification I - Philadelphia (PH)+

Idarubicin DRUG

Stratification II - SR/HR/PH+ + MRD-pos

Dexamethasone DRUG

Randomisation II - HR + MRD-neg-SR-chemo; Stratification I - Philadelphia (PH)+; Stratification I - Standard Risk (SR)/ High Risk (HR); Stratification II - SR + MRD-neg

Cyclophosphamide DRUG

Randomisation II - HR + MRD-neg-SR-chemo; Stratification I - Standard Risk (SR)/ High Risk (HR); Stratification II - HR + MRD-neg; Stratification II - SR + MRD-neg

Fludarabine DRUG

Stratification II - SR/HR/PH+ + MRD-pos

Vincristine DRUG

Stratification I - Philadelphia (PH)+; Stratification I - Standard Risk (SR)/ High Risk (HR)

Mercaptopurine DRUG

Stratification I - Standard Risk (SR)/ High Risk (HR)

VP16 DRUG

Stratification I - Philadelphia (PH)+; Stratification I - Standard Risk (SR)/ High Risk (HR)

Daunorubicin (DNR) DRUG

Stratification I - Standard Risk (SR)/ High Risk (HR)

Methotrexate DRUG

Rand I - B-Lin + CNS Rad + i.th. MTX; Rand I - B-Lin + i.th. MTX; Randomisation II - HR + MRD-neg-SR-chemo; Stratification I - Philadelphia (PH)+; Stratification I - Standard Risk (SR)/ High Risk (HR); Stratification II - HR + MRD-neg; Stratification II - SR + MRD-neg

Stem cell transplantation PROCEDURE

Randomisation II - HR + MRD-neg-SCT; Stratification II - HR + MRD-neg

Cytarabine DRUG

Randomisation II - HR + MRD-neg-SR-chemo; Stratification I - Philadelphia (PH)+; Stratification I - Standard Risk (SR)/ High Risk (HR); Stratification II - HR + MRD-neg; Stratification II - SR + MRD-neg; Stratification II - SR/HR/PH+ + MRD-pos

Adriamycin DRUG

Randomisation II - HR + MRD-neg-SR-chemo; Stratification II - HR + MRD-neg; Stratification II - SR + MRD-neg

Prednisolone DRUG

Randomisation II - HR + MRD-neg-SR-chemo; Stratification II - HR + MRD-neg; Stratification II - SR + MRD-neg

Vindesine DRUG

Randomisation II - HR + MRD-neg-SR-chemo; Stratification I - Philadelphia (PH)+; Stratification I - Standard Risk (SR)/ High Risk (HR); Stratification II - HR + MRD-neg; Stratification II - SR + MRD-neg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Acute lymphoblastic leukemia (pro-B, common, pre-B, early T, thymic T, mature T)
• Lymphoblastic lymphoma (B or T-lineage)
• Age 18-55 yrs
• Written informed consent
• Adequate contraception as specified per protocol

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 or breast feeding
• 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

Study Sites (1)

University Hospital of Frankfurt (Main)

Frankfurt am Main, 60590, Germany

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Rituximab; nelarabine; pegaspargase; Cranial Irradiation; Imatinib Mesylate; Idarubicin; Dexamethasone; Cyclophosphamide; fludarabine; Vincristine; Mercaptopurine; Etoposide; Daunorubicin; Methotrexate; Stem Cell Transplantation; Cytarabine; Vindesine; Doxorubicin; Prednisolone

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics; Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Sulfhydryl Compounds; Sulfur Compounds; Purines; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Aminopterin; Pterins; Pteridines; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative; Cytidine; Pyrimidine Nucleosides; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Nicola Gökbuget, Dr. med.

  University Hospital of Frankfurt (Main)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: GMALL Head

Study Record Dates

• First Submitted: August 4, 2016
• First Posted: August 26, 2016
• Study Start: August 1, 2016
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: December 16, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)