acute lymphoblastic leukemia (including acute biphenotypic leukemia) in infants <1 year of age MedDRA version: 14.1 Level: LLT Classification code 10000845 Term: Acute lymphoblastic leukemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: CYTOSAR
Product Name: Cytarabine (TEST) IV
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Cytarabine
CAS Number: 147944
Concentration unit: mg/m2 milligram(s)/square mete
Sponsors
Dutch Childhood Oncology Group
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Children aged 365 days or less with newly diagnosed acute lymphoblastic leukemia (ALL) or biphenotypic leukemia according to EGIL criteria. Children with CNS or testicular leukemia at diagnosis are eligible. 2. Morphological verification of the diagnosis, confirmed with cytochemistry and immunophenotyping. In case a bone marrow aspiration results in a “dry tap”, a trephine biopsy is advised unless it is possible to confirm the diagnosis by peripheral blood examination. 3. Informed consent of the parents or other legally authorized guardian of the patient. 4. Mandatory guidelines as per Amendment 23 May 2012. 5. An amendment to the Stem Cell Transplantation (SCT) regimen was made on the 23 May 2012 because of the high SCT related mortality. 5.a The SCT conditioning regimen Busulfan Cyclofosfamide-Melphalan will be replaced by the less toxic conditioning regimen iv Busulfan (or Treosulfan), Fludarabine and Thiotepa. 5.b. It is advised to refer infant Acute Lymphoblastic Leukemia (ALL) cases to SCT to large experienced transplant centers. Are the trial subjects under 18? yes Number of subjects for this age range: 445 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Mature B-ALL, defined by the immunophenotypical presence of surface immunoglobulines or t(8;14) and breakpoint as in B-ALL. 2. the presence of the t(9;22) (q34;q11) or bcr-abl fusion in the leukemic cells (if these data are not known, the patient is eligible). 3. Age > 365 days 4. Relapsed ALL 5. Systemic use of corticosteroids less than 4 weeks before diagnosis. Patients who received corticosteroids by aerosol are eligible for the study. 6. HR patients who have MRD level of <10e-4 by PCR at the start of OCTADA(D) will not be eligible for mismatched donor transplant.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the role of an early intensification of two "AML" induction blocks versus protocol Ib directly after induction, in a randomized way in MR and HR patients.;Secondary Objective: 1. To assess the role of an early intensification of two "AML" induction blocks versus protocol Ib directly after induction, in a randomized way in MR and HR patients, separately. 2. To assess the overall outcome of the Interfant-06 protocol compared to the historical control series, especially the Interfant-99. 3. To assess the outcome of LR, MR and HR patients as compared to the historical control series in Interfant-99. 4. To study which factors have independent prognostic value. 5. To assess the role of SCT in HR patients and MR patients with MRD levels of = 10e-4 at the start of OCTADA(D) ;Primary end point(s): 1. Primary endpoint for the randomized question (primary aim) will be the Disease Free Survival (DFS). DFS is defined as the time from randomization to relapse, second malignancy or death, whichever occurs first. 2. Primary endpoint for the comparison with historical controls (secondary aim) will be the Event Free Survival (EFS). EFS is defined as the time from diagnosis to early death, resistance to induction, relapse, second malignancy or death in complete remission, whichever occurs first. Secondary endpoint will be survival from date of diagnosis to death from any cause. 3.a. It is mandatory to give antibiotic and antifungal prophylaxis during and after the intensive chemotherapy courses induction, IB, ADE, MAE, MARMA and OCTADA(D) until recovery of neutrophils. Advice is to use ciprofloxacin and itraconazol but alternative prophylaxis can be used according to national or international guidelines. Itraconazol should not be given in combination with weekly vincristine (induction first weeks of OCTADA(D)) because the interaction may lead to increased neurotoxicity. 3.b. Patients should be kept in the hospital after intensive therapy courses or they sh | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoint will be survival from date of randomization to death from any cause. Assessment of the results of the randomized question will also be performed within MR and HR patients separately.;Timepoint(s) of evaluation of this end point: 1. The evaluation of outcome will also be performed in terms of survival time from diagnosis (endpoint is death for any cause). 2. The evaluation of SCT will be done primarily according to the “intention to treat” principle, comparing the DFS in patients who have a suitable donor with those for whom no donor was found, regardless of whether they actually received SCT. Secondarily, analysis will also be done by treatment performed. This latter analysis will be adjusted by waiting time to SCT P52. | — |
Countries
Austria, Belgium, Denmark, France, Germany, Ireland, Italy, Portugal, United Kingdom
Contacts
Public ContactDCOG
Dutch Childhood Oncology Group
Outcome results
None listed