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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Stratification I - Standard Risk (SR)/ High Risk (HR)<br>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<br> <br> Drug: PEG-Asparaginase<br> <br> Drug: Dexamethasone<br> <br> Drug: Cyclophosphamide<br> <br> Drug: Vincristine<br> <br> Drug: Mercaptopurine<br> <br> Drug: VP16<br> <br> Drug: Daunorubicin (DNR)<br> <br> Drug: Methotrexate<br> <br> Drug: Cytarabine<br> <br> Drug: Vindesine<br> <br> |
| Other: Stratification I - Philadelphia (PH)+<br>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<br> <br> Drug: PEG-Asparaginase<br> <br> Drug: Imatinib<br> <br> Drug: Dexamethasone<br> <br> Drug: Vincristine<br> <br> Drug: VP16<br> <br> Drug: Methotrexate<br> <br> Drug: Cytarabine<br> <br> Drug: Vindesine<br> <br> |
| Active Comparator: Rand I - B-Lin + CNS Rad + i.th. MTX<br>Chemotherapy according to Stratification I SR/HR CNS prophylaxis: CNS irradiation 24 Gy, intrathecal Methotrexate | Procedure: Cranial irradiation<br> <br> Drug: Methotrexate<br> <br> |
| Experimental: Rand I - B-Lin + i.th. MTX<br>Chemotherapy according to Stratification I SR/HR CNS prophylaxis: intrathecal Methotrexate | Drug: Methotrexate<br> <br> |
| Other: Stratification II - SR + MRD-neg<br>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<br> <br> Drug: Nelarabine<br> <br> Drug: PEG-Asparaginase<br> <br> Drug: Dexamethasone<br> <br> Drug: Cyclophosphamide<br> <br> Drug: Methotrexate<br> <br> Drug: Cytarabine<br> <br> Drug: Vindesine<br> <br> Drug: Adriamycin<br> <br> Drug: Prednisolone<br> <br> |
| Other: Stratification II - HR + MRD-neg<br>Chemotherapy or stem cell transplantation according to randomisation II | Drug: Rituximab<br> <br> Drug: Nelarabine<br> <br> Drug: PEG-Asparaginase<br> <br> Drug: Cyclophosphamide<br> <br> Drug: Methotrexate<br> <br> Procedure: Stem cell transplantation<br> <br> Drug: Cytarabine<br> <br> Drug: Vindesine<br> <br> Drug: Adriamycin<br> <br> Drug: Prednisolone<br> <br> |
| Other: Stratification II - SR/HR/PH+ + MRD-pos<br>Chemotherapy or targeted therapy, followed by stem cell transplantation Drugs: Fludarabine, Idarubicin, Cytarabine, Nelarabine | Drug: Nelarabine<br> <br> Drug: Idarubicin<br> <br> Drug: Fludarabine<br> <br> Drug: Cytarabine<br> <br> |
| Active Comparator: Randomisation II - HR + MRD-neg-SCT<br>Stem cell transplantation | Procedure: Stem cell transplantation<br> <br> |
| Experimental: Randomisation II - HR + MRD-neg-SR-chemo<br>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<br> <br> Drug: Nelarabine<br> <br> Drug: PEG-Asparaginase<br> <br> Drug: Dexamethasone<br> <br> Drug: Cyclophosphamide<br> <br> Drug: Methotrexate<br> <br> Drug: Cytarabine<br> <br> Drug: Vindesine<br> <br> Drug: Adriamycin<br> <br> Drug: Prednisolone<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event free survival |  | 3.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time until consolidation treatment I |  | approximately 70 days | 
| Disease free survival |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRD, Acute lymphoblastic leukemia, Lymphoblastic lymphoma, Nelarabine, BCR-ABL, PEG-Asparaginase, Rituximab