International Collaborative Treatment Protocol For Children And Adolescents With Acute Lymphoblastic Leukemia

• Status: Active, not recruiting
• Trial end date: 2021-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Rationale/Purpose: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating young patients with acute lymphoblastic leukemia (ALL).

This trial is studying several different combination chemotherapy regimens to compare how well they work in treating young patients with ALL.

Study objectives

Primary study questions:

• Non high-risk (non-HR) precursor-B ALL (pB-ALL) patients with TEL/AML1-negative ALL or unknown TEL/AML1 status and flow cytometry minimal residual disease (MRD) in bone marrow on day 15 <0.1% or with TEL/AML1-positive ALL (randomized study question R1): Can the daunorubicin dose in Protocol IA be safely reduced by 50 % with a non-inferior EFS and a reduction of toxicity (treatment-related mortality and AE/SAE in Protocol I)?

• Patients with pB-ALL and risk group medium risk (MR) (randomized study question R2): Can the clinical outcome be improved by protracted asparagine depletion achieved through application of intensified PEG-L-asparaginase during reintensification and early maintenance?

• High-risk (HR) patients (as identified by day 33 - randomized study question RHR): Can the clinical outcome be improved by protracted exposure to PEG-L-asparaginase during Protocol IB?

Secondary study questions:

• Standard risk (SR) patients identified by at least one sensitive marker: Is the clinical outcome comparable to that obtained in SR patients (identified with two sensitive markers) in AIEOP-BFM ALL 2000, or can the outcome even be improved with the use of PEG-L-asparaginase instead of native E. coli L-ASP?

• T-ALL non-HR patients: Can the high level of outcome which was obtained for these patients in study AIEOP-BFM ALL 2000 be preserved or even improved with the use of PEG-L-ASP instead of native E. coli L-ASP?

• HR patients with persisting high MRD levels despite the use of the HR blocks in the intensified consolidation phase "MRD Non-Responders": Is it possible to improve the outcome and to achieve a further reduction of leukemic cell burden by administration of an innovative treatment schedule (DNX-FLA)?

• Patients participating in the randomized asparaginase studies (pB-ALL/MR, HR): Are asparaginase activity and asparaginase antibodies associated with development of allergic reactions, and do they have an effect on the outcome of the patients?

• What is the relative value of different methods of MRD monitoring in the definition of alternative stratification systems within a BFM-oriented protocol?

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital Schleswig-Holstein; University of Schleswig-Holstein
• Collaborator: Deutsche Krebshilfe e.V., Bonn (Germany)
• Treatments: 6-Mercaptopurine; Asparaginase; Cyclophosphamide; Cytarabine; Daunorubicin; Dexamethasone; Doxorubicin; Etoposide; Fludarabine; Ifosfamide; Liposomal doxorubicin; Mercaptopurine; Methotrexate; Pegaspargase; Prednisone; Thioguanine; Vincristine; Vindesine

Criteria

Inclusion Criteria:

• newly diagnosed acute lymphoblastic leukemia

• age ≥ 1 year (> 365 days) and < 18 years old (up to 17 years old and 365 days)

• no Ph+ (BCR/ABL or t(9;22)-positive) ALL

• no evidence of pregnancy or lactation period

• no participation in another clinical study

• patient enrolled in a participating center

• written informed consent

Exclusion Criteria:

• pre-treatment with cytostatic drugs

• pre-treatment with cytostatic drugs

• steroid pre-treatment with ≥ 1 mg/kg/d for more than two weeks during the last month before diagnosis

• treatment started according to another protocol

• underlying diseases that prohibit treatment according to the protocol

• ALL diagnosed as second malignancy steroid pre-treatment with ≥ 1 mg/kg/d for more than two weeks during the last month before diagnosis