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

Phase 3

Active, not recruiting

• Conditions: Acute Lymphoblastic Leukemia; Lymphoblastic Lymphoma
• Interventions: Drug: Rituximab; Procedure: Cranial irradiation; Drug: Nelarabine; Drug: Idarubicin; Drug: PEG-Asparaginase; Drug: Imatinib; Drug: Fludarabine; Drug: Dexamethasone; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Methotrexate; Procedure: Stem cell transplantation; Drug: Mercaptopurine; Drug: Cytarabine; Drug: VP16; Drug: Vindesine; Drug: Daunorubicin (DNR); Drug: Adriamycin; Drug: Prednisolone

• Registration Number: NCT02881086
• Lead Sponsor: Goethe University

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 r...

Detailed Description

Not available

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study Start: 2016-08
• Study First Submitted: 2016-08-04
• Study First Submitted QC: 2016-08-23
• Study First Posted: 2016-08-26
• Primary Completion: 2022-08
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-09
• Last Update Posted: 2024-10-10
• Study Completion: 2025-07

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 1000

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Stratification II - SR + MRD-neg	Cyclophosphamide	Chemotherapy, immunotherapy, intrathecal prophylaxis, consolidation II, reinduction, consolidation III - VI, maintenance Drugs: Rituximab, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, Adriamycin, Prednisolone, Cyclophosphamide, Nelarabine, Dexamethasone
Stratification II - SR + MRD-neg	Methotrexate	Chemotherapy, immunotherapy, intrathecal prophylaxis, consolidation II, reinduction, consolidation III - VI, maintenance Drugs: Rituximab, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, Adriamycin, Prednisolone, Cyclophosphamide, Nelarabine, Dexamethasone
Stratification II - SR + MRD-neg	Cytarabine	Chemotherapy, immunotherapy, intrathecal prophylaxis, consolidation II, reinduction, consolidation III - VI, maintenance Drugs: Rituximab, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, Adriamycin, Prednisolone, Cyclophosphamide, Nelarabine, Dexamethasone
Stratification II - HR + MRD-neg	Rituximab	Chemotherapy or stem cell transplantation according to randomisation II
Stratification II - HR + MRD-neg	Nelarabine	Chemotherapy or stem cell transplantation according to randomisation II
Stratification II - HR + MRD-neg	Stem cell transplantation	Chemotherapy or stem cell transplantation according to randomisation II
Stratification II - SR + MRD-neg	Adriamycin	Chemotherapy, immunotherapy, intrathecal prophylaxis, consolidation II, reinduction, consolidation III - VI, maintenance Drugs: Rituximab, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, Adriamycin, Prednisolone, Cyclophosphamide, Nelarabine, Dexamethasone
Stratification II - SR + MRD-neg	Prednisolone	Chemotherapy, immunotherapy, intrathecal prophylaxis, consolidation II, reinduction, consolidation III - VI, maintenance Drugs: Rituximab, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, Adriamycin, Prednisolone, Cyclophosphamide, Nelarabine, Dexamethasone
Stratification II - SR + MRD-neg	Vindesine	Chemotherapy, immunotherapy, intrathecal prophylaxis, consolidation II, reinduction, consolidation III - VI, maintenance Drugs: Rituximab, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, Adriamycin, Prednisolone, Cyclophosphamide, Nelarabine, Dexamethasone
Stratification II - HR + MRD-neg	Vindesine	Chemotherapy or stem cell transplantation according to randomisation II
Stratification II - HR + MRD-neg	Adriamycin	Chemotherapy or stem cell transplantation according to randomisation II
Stratification II - HR + MRD-neg	Prednisolone	Chemotherapy or stem cell transplantation according to randomisation II
Stratification II - SR/HR/PH+ + MRD-pos	Nelarabine	Chemotherapy or targeted therapy, followed by stem cell transplantation Drugs: Fludarabine, Idarubicin, Cytarabine, Nelarabine
Stratification II - SR/HR/PH+ + MRD-pos	Idarubicin	Chemotherapy or targeted therapy, followed by stem cell transplantation Drugs: Fludarabine, Idarubicin, Cytarabine, Nelarabine
Randomisation II - HR + MRD-neg-SCT	Stem cell transplantation	Stem cell transplantation
Randomisation II - HR + MRD-neg-SR-chemo	Vindesine	Chemotherapy, immunotherapy, intrathecal prophylaxis, consolidation II, reinduction, consolidation III - VI, maintenance Drugs: Rituximab, Dexamethasone, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, Adriamycin, Prednisolone, Cyclophosphamide, Nelarabine
Randomisation II - HR + MRD-neg-SR-chemo	Methotrexate	Chemotherapy, immunotherapy, intrathecal prophylaxis, consolidation II, reinduction, consolidation III - VI, maintenance Drugs: Rituximab, Dexamethasone, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, Adriamycin, Prednisolone, Cyclophosphamide, Nelarabine
Randomisation II - HR + MRD-neg-SR-chemo	Rituximab	Chemotherapy, immunotherapy, intrathecal prophylaxis, consolidation II, reinduction, consolidation III - VI, maintenance Drugs: Rituximab, Dexamethasone, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, Adriamycin, Prednisolone, Cyclophosphamide, Nelarabine
Randomisation II - HR + MRD-neg-SR-chemo	Nelarabine	Chemotherapy, immunotherapy, intrathecal prophylaxis, consolidation II, reinduction, consolidation III - VI, maintenance Drugs: Rituximab, Dexamethasone, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, Adriamycin, Prednisolone, Cyclophosphamide, Nelarabine
Randomisation II - HR + MRD-neg-SR-chemo	Dexamethasone	Chemotherapy, immunotherapy, intrathecal prophylaxis, consolidation II, reinduction, consolidation III - VI, maintenance Drugs: Rituximab, Dexamethasone, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, Adriamycin, Prednisolone, Cyclophosphamide, Nelarabine
Randomisation II - HR + MRD-neg-SR-chemo	Cytarabine	Chemotherapy, immunotherapy, intrathecal prophylaxis, consolidation II, reinduction, consolidation III - VI, maintenance Drugs: Rituximab, Dexamethasone, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, Adriamycin, Prednisolone, Cyclophosphamide, Nelarabine
Stratification I - Standard Risk (SR)/ High Risk (HR)	Rituximab	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
Stratification I - Standard Risk (SR)/ High Risk (HR)	PEG-Asparaginase	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
Stratification I - Standard Risk (SR)/ High Risk (HR)	Dexamethasone	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
Stratification I - Standard Risk (SR)/ High Risk (HR)	Cyclophosphamide	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
Stratification I - Standard Risk (SR)/ High Risk (HR)	VP16	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
Stratification I - Standard Risk (SR)/ High Risk (HR)	Daunorubicin (DNR)	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
Stratification I - Philadelphia (PH)+	Rituximab	Induction and consolidation I therapy for PH+ patients Chemotherapy, immunotherapy, intrathecal prophylaxis Drugs: Rituximab, Vincristine, Imatinib, Dexamethasone, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, VP16
Stratification I - Philadelphia (PH)+	PEG-Asparaginase	Induction and consolidation I therapy for PH+ patients Chemotherapy, immunotherapy, intrathecal prophylaxis Drugs: Rituximab, Vincristine, Imatinib, Dexamethasone, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, VP16
Stratification I - Philadelphia (PH)+	Imatinib	Induction and consolidation I therapy for PH+ patients Chemotherapy, immunotherapy, intrathecal prophylaxis Drugs: Rituximab, Vincristine, Imatinib, Dexamethasone, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, VP16
Stratification I - Philadelphia (PH)+	Dexamethasone	Induction and consolidation I therapy for PH+ patients Chemotherapy, immunotherapy, intrathecal prophylaxis Drugs: Rituximab, Vincristine, Imatinib, Dexamethasone, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, VP16
Stratification I - Philadelphia (PH)+	Vincristine	Induction and consolidation I therapy for PH+ patients Chemotherapy, immunotherapy, intrathecal prophylaxis Drugs: Rituximab, Vincristine, Imatinib, Dexamethasone, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, VP16
Stratification I - Philadelphia (PH)+	VP16	Induction and consolidation I therapy for PH+ patients Chemotherapy, immunotherapy, intrathecal prophylaxis Drugs: Rituximab, Vincristine, Imatinib, Dexamethasone, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, VP16
Stratification I - Philadelphia (PH)+	Methotrexate	Induction and consolidation I therapy for PH+ patients Chemotherapy, immunotherapy, intrathecal prophylaxis Drugs: Rituximab, Vincristine, Imatinib, Dexamethasone, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, VP16
Stratification I - Philadelphia (PH)+	Cytarabine	Induction and consolidation I therapy for PH+ patients Chemotherapy, immunotherapy, intrathecal prophylaxis Drugs: Rituximab, Vincristine, Imatinib, Dexamethasone, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, VP16
Stratification I - Philadelphia (PH)+	Vindesine	Induction and consolidation I therapy for PH+ patients Chemotherapy, immunotherapy, intrathecal prophylaxis Drugs: Rituximab, Vincristine, Imatinib, Dexamethasone, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, VP16
Rand I - B-Lin + CNS Rad + i.th. MTX	Cranial irradiation	Chemotherapy according to Stratification I SR/HR CNS prophylaxis: CNS irradiation 24 Gy, intrathecal Methotrexate
Rand I - B-Lin + CNS Rad + i.th. MTX	Methotrexate	Chemotherapy according to Stratification I SR/HR CNS prophylaxis: CNS irradiation 24 Gy, intrathecal Methotrexate
Rand I - B-Lin + i.th. MTX	Methotrexate	Chemotherapy according to Stratification I SR/HR CNS prophylaxis: intrathecal Methotrexate
Stratification II - SR + MRD-neg	PEG-Asparaginase	Chemotherapy, immunotherapy, intrathecal prophylaxis, consolidation II, reinduction, consolidation III - VI, maintenance Drugs: Rituximab, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, Adriamycin, Prednisolone, Cyclophosphamide, Nelarabine, Dexamethasone
Stratification II - SR + MRD-neg	Dexamethasone	Chemotherapy, immunotherapy, intrathecal prophylaxis, consolidation II, reinduction, consolidation III - VI, maintenance Drugs: Rituximab, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, Adriamycin, Prednisolone, Cyclophosphamide, Nelarabine, Dexamethasone
Stratification II - HR + MRD-neg	Methotrexate	Chemotherapy or stem cell transplantation according to randomisation II
Stratification I - Standard Risk (SR)/ High Risk (HR)	Vincristine	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
Stratification I - Standard Risk (SR)/ High Risk (HR)	Mercaptopurine	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
Stratification I - Standard Risk (SR)/ High Risk (HR)	Methotrexate	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
Stratification I - Standard Risk (SR)/ High Risk (HR)	Cytarabine	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
Stratification I - Standard Risk (SR)/ High Risk (HR)	Vindesine	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
Stratification II - SR + MRD-neg	Nelarabine	Chemotherapy, immunotherapy, intrathecal prophylaxis, consolidation II, reinduction, consolidation III - VI, maintenance Drugs: Rituximab, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, Adriamycin, Prednisolone, Cyclophosphamide, Nelarabine, Dexamethasone
Stratification II - SR + MRD-neg	Rituximab	Chemotherapy, immunotherapy, intrathecal prophylaxis, consolidation II, reinduction, consolidation III - VI, maintenance Drugs: Rituximab, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, Adriamycin, Prednisolone, Cyclophosphamide, Nelarabine, Dexamethasone
Stratification II - HR + MRD-neg	Cyclophosphamide	Chemotherapy or stem cell transplantation according to randomisation II
Stratification II - HR + MRD-neg	PEG-Asparaginase	Chemotherapy or stem cell transplantation according to randomisation II
Stratification II - HR + MRD-neg	Cytarabine	Chemotherapy or stem cell transplantation according to randomisation II
Stratification II - SR/HR/PH+ + MRD-pos	Fludarabine	Chemotherapy or targeted therapy, followed by stem cell transplantation Drugs: Fludarabine, Idarubicin, Cytarabine, Nelarabine
Stratification II - SR/HR/PH+ + MRD-pos	Cytarabine	Chemotherapy or targeted therapy, followed by stem cell transplantation Drugs: Fludarabine, Idarubicin, Cytarabine, Nelarabine
Randomisation II - HR + MRD-neg-SR-chemo	PEG-Asparaginase	Chemotherapy, immunotherapy, intrathecal prophylaxis, consolidation II, reinduction, consolidation III - VI, maintenance Drugs: Rituximab, Dexamethasone, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, Adriamycin, Prednisolone, Cyclophosphamide, Nelarabine
Randomisation II - HR + MRD-neg-SR-chemo	Cyclophosphamide	Chemotherapy, immunotherapy, intrathecal prophylaxis, consolidation II, reinduction, consolidation III - VI, maintenance Drugs: Rituximab, Dexamethasone, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, Adriamycin, Prednisolone, Cyclophosphamide, Nelarabine
Randomisation II - HR + MRD-neg-SR-chemo	Adriamycin	Chemotherapy, immunotherapy, intrathecal prophylaxis, consolidation II, reinduction, consolidation III - VI, maintenance Drugs: Rituximab, Dexamethasone, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, Adriamycin, Prednisolone, Cyclophosphamide, Nelarabine
Randomisation II - HR + MRD-neg-SR-chemo	Prednisolone	Chemotherapy, immunotherapy, intrathecal prophylaxis, consolidation II, reinduction, consolidation III - VI, maintenance Drugs: Rituximab, Dexamethasone, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, Adriamycin, Prednisolone, Cyclophosphamide, Nelarabine

Primary Outcome Measures

Name	Time	Method
Event free survival	3.5 years

Secondary Outcome Measures

Name	Time	Method
Disease free survival	1 year
Time until consolidation treatment I	approximately 70 days

Trial Locations

Locations (1)

University Hospital of Frankfurt (Main); 🇩🇪 Frankfurt (Main), Germany