Acute lymphoblastic leukemia MedDRA version: 14.1 Level: LLT Classification code 10000845 Term: Acute lymphoblastic leukemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Methotrexate
Pharmaceutical Form: Injection
INN or Proposed INN: METHOTREXATE
CAS Number: 59-05-2
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentratio
Sponsors
Vilnius University Hospital Santariskiu Clinics
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Non B-ALL 2. Non Ph+ ALL 3. Age 18-45 years of age. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Bilineage ALL. 2. Pre-treatment with glucocorticosteroids or other antileukemic agents. Patients, who have been treated with systemic glucocorticosteroids or other anticancer agents (e.g. methotrexate or thiopurines) for more than a week prior to the diagnosis of ALL and initiation of antileukemic therapy, can be treated by the NOPHO ALL-2008 protocol and will be registered, but they cannot be included in the randomised trials. 3. Incomplete exploration for the risk group stratifying cytogenetic aberrations. 4. ALL predisposition syndromes. Patients with certain ALL-predisposing disorders (e.g. Down syndrome, Ataxia Telangiectasia) can be entered into the protocol with the amendments outlined in section 16, but can not be included in the randomised trials. 5. Previous cancer. Patients who have previously been treated for a malignant neoplasm can be treated by the NOPHO ALL-2008 protocol and will be registered, but they cannot be included in the randomised trials (see section 16). They will be treated according to the control arms of the protocol. 6. Intolerance to one or more anticancer agent. 7. Administration of additional chemotherapy during induction therapy for non-HR ALL. Patients with non-HR ALL, who at day 15 have a M3 bone marrow should not be given additional chemotherapy. If given, the patients will not be eligible for the SR-ALL treatment arm and the patient will not be eligible for randomisation. 8. Sexually active females not using contraception. 9. TPMT-deficiency (6MP-randomisation only). 10. DepoCyte during induction therapy (DepoCyte randomisation only)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To increase the fraction of patients, who become MRD-negative during consolidation for the non-HR ALL group through individualised intensification of the 6MP-dosage days 30-85. We will additionally measure EFS and toxicity as secondary end points of effect. 2. To test if intramuscular PEG-asparaginase administered either at six or two week intervals from day 92 until 8 months from diagnosis for patients with non-HR ALL will result in equal probability of EFS. As secondary endpoints asparaginase antibody production and toxicity including allergic reactions in the treatment-arms will be analysed. 3. To test if replacing six doses of conventional triple i.t. therapy with DepoCyte® during maintenance therapy for HR-ALL will yield an equal or reduced rate of serious toxicity (SAEs and SUSARs) with a similar or decreased CNS- and overall relapse rate.;Secondary Objective: 1. Patients with lower risk features at diagnosis (B-lineage ALL and WBC 25% leukemic blasts at day 15 and <5% leukemic blasts day 29), have a worse cure rate than patients with a fast bone-marrow response (<25% leukemic blasts at day 15 and <5% leukemic blasts day 29). 2. patients with T-lineage ALL and a d29 MRD-level <10-3 can be treated according to the IR-ALL strategy and obtain an EFS that is not significantly lower than that of B-precursor ALL patients with IR-ALL. 3. patients with CNS3 and no HR-ALL risk factors at diagnosis can be treated according to the IR-ALL strategy without radiotherapy and obtain an EFS that is not different from that of the remaining patients with IR-ALL and not inferior to CNS-positive patients treated according to the current ALL-2000 protocol.;Primary end point(s): A. Reduction of relapse rate and/or level of residual disease without an unacceptable increase in toxicitý. OR B. Equal rate of relapse with a reduction of rate of significant toxicities;Timepoint(s) of evaluation of this end point: 15th, 29th and 79th days | — |
Countries
Lithuania
Contacts
Public ContactTadas Zvirblis
Vilnius University Hospital Santariskiu Clinics
Outcome results
None listed