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

Sponsor

Goethe University (Other)

Overall Status

Recruiting

CT.gov ID

NCT02881086

Collaborator

(none)

900

Enrollment

Location

Arms

107

Duration (Months)

8.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Lymphoblastic Leukemia Lymphoblastic Lymphoma	Drug: Rituximab Drug: Nelarabine Drug: PEG-Asparaginase Procedure: Cranial irradiation Drug: Imatinib Drug: Idarubicin Drug: Dexamethasone Drug: Cyclophosphamide Drug: Fludarabine Drug: Vincristine Drug: Mercaptopurine Drug: VP16 Drug: Daunorubicin (DNR) Drug: Methotrexate Procedure: Stem cell transplantation Drug: Cytarabine Drug: Vindesine Drug: Adriamycin Drug: Prednisolone	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

900 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Treatment Optimization in Adult Patients With Newly Diagnosed Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma by Individualised, Targeted and Intensified Treatment - a Phase IV-trial With a Phase III-part to Evaluate Safety and Efficacy of Nelarabine in T-ALL Patients

Study Start Date :

Aug 1, 2016

Anticipated Primary Completion Date :

Jul 1, 2022

Anticipated Study Completion Date :

Jul 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Other: Stratification I - Standard Risk (SR)/ High Risk (HR) 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
Other: Stratification I - Philadelphia (PH)+ 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
Active Comparator: Rand I - B-Lin + CNS Rad + i.th. MTX Chemotherapy according to Stratification I SR/HR CNS prophylaxis: CNS irradiation 24 Gy, intrathecal Methotrexate	Procedure: Cranial irradiation Drug: Methotrexate
Experimental: Rand I - B-Lin + i.th. MTX Chemotherapy according to Stratification I SR/HR CNS prophylaxis: intrathecal Methotrexate	Drug: Methotrexate
Other: Stratification II - SR + MRD-neg 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
Other: Stratification II - HR + MRD-neg 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
Other: Stratification II - SR/HR/PH+ + MRD-pos Chemotherapy or targeted therapy, followed by stem cell transplantation Drugs: Fludarabine, Idarubicin, Cytarabine, Nelarabine	Drug: Nelarabine Drug: Idarubicin Drug: Fludarabine Drug: Cytarabine
Active Comparator: Randomisation II - HR + MRD-neg-SCT Stem cell transplantation	Procedure: Stem cell transplantation
Experimental: Randomisation II - HR + MRD-neg-SR-chemo 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

Outcome Measures

Primary Outcome Measures

Event free survival [3.5 years]

Secondary Outcome Measures

Time until consolidation treatment I [approximately 70 days]
Disease free survival [1 year]

Other Outcome Measures

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]
Remission duration [up to 10 years]
Relapse rate [up to 10 years]
Overall survival [up to 10 years]
Relapse location [at timepoint of relapse (up to 10 years)]
Early death [during induction, approximately 6-8 weeks from diagnosis]
Death in clinical remission (CR) [during treatment, up to approximately 2.5 years from diagnosis]
Comorbidities according to Charlson Score [up to 2.5 years]
Quality of life assessed by QLQ-C30 [up to 2.5 years]
Eastern Cooperative Oncology Group (ECOG) under therapy [up to 2.5 years]
Toxicity assessed by CTCAE v4.03 [up to 2.5 years]
Results of the Dementia Detection (DemTect) test [up to 2.5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 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)
Lymphoblastic lymphoma (B or T-lineage)
Age 18-55 yrs
Written informed consent
Adequate contraception as specified per protocol

Exclusion Criteria:

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