This phase III trial compares the effect of usual treatment of chemotherapy and steroids and a tyrosine kinase inhibitor (TKI) to the same treatment plus blinatumomab. Blinatumomab is a Bi-specific T-Cell Engager ('BiTE') that may interfere with the ability of cancer cells to grow and spread. The information gained from this study may help researchers determine if combination therapy with steroids, TKIs, and blinatumomab work better than the standard of care.
Name: Blinatumomab
Name: Cyclophosphamide
Name: Cytarabine
Name: Dasatinib
Name: Dexamethasone
Name: Doxorubicin Hydrochloride
Name: Mesna
Name: Methotrexate
Name: Ponatinib Hydrochloride
Name: Prednisone
Name: Vincristine Sulfate
Description: Will compare OS following induction with steroids + tyrosine kinase inhibitor (TKI) + blinatumomab and induction with steroids + TKI + chemotherapy. Will be based on an intent-to-treat analysis. Estimates of OS including medians and confidence intervals, will be calculated using the Kaplan-Meier method. Comparisons of OS between treatment arms will be conducted using the one-sided stratified log-rank test with steroid responsiveness, type of TKI intended to receive and age at diagnosis, the same factors used in randomization, as stratification factors. Cox proportional hazards models of OS, stratified on the same factors used in the randomization, will be used to assess the effect of treatment by adjusting other possible clinical and biological risk factors, including cytogenetic abnormalities.
Measure: Overall survival (OS) Time: Time between randomization and death from any cause, assessed up to 10 years from the date of registrationDescription: Will be centrally evaluated. Will be compared between two arms using Fisher's exact test with a one-sided type I error rate of 2.5%. Multivariable logistic regression modeling will be used to adjust for other possible clinical and biological risk factors. For patients registered to Step 3 (re-induction), the rates of MRD negativity and their corresponding 95% confidence intervals after re-induction will be given by treatment arm.
Measure: Rate of minimal residual disease (MRD) negativity Time: At week 15Description: Will be based on an intent-to-treat analysis. Estimates of EFS including medians and confidence intervals, will be calculated using the Kaplan-Meier method. Comparisons of EFS between treatment arms will be conducted using the one-sided stratified log-rank test with steroid responsiveness, type of TKI intended to receive and age at diagnosis, the same factors used in randomization, as stratification factors. Cox proportional hazards models of EFS, stratified on the same factors used in the randomization, will be used to assess the effect of treatment by adjusting other possible clinical and biological risk factors, including cytogenetic abnormalities
Measure: Event free survival (EFS) Time: Time from randomization to failure to achieve induction molecular remission by week 15, confirmed molecular relapse after molecular remission or to death in remission, assessed up to 10 years from the date of registrationDescription: Will be centrally evaluated. Will be compared between two arms using Fisher's exact test with a one-sided type I error rate of 2.5%. Multivariable logistic regression modeling will be used to adjust for other possible clinical and biological risk factors. For patients registered to Step 3 (re-induction), the rates of MRD negativity and their corresponding 95% confidence intervals after re-induction will be given by treatment arm.
Measure: Rate of MRD negativity Time: After re-induction and safetyDescription: All toxicity grades and reportable adverse events will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Measure: Incidence of adverse events Time: Up to 10 years from the date of registrationAllocation: Randomized
Crossover Assignment
There is one SNP
To be eligible for this trial, patients must be class 2B or better - Investigators must confirm which TKI patient is to receive - NOTE: Patients with known T315I mutation status should receive ponatinib treatment - NOTE: In situations due to insurance coverage issues and the pre-selected TKI is not immediately available, patients can receive dasatinib or imatinib during Step 1. --- T315I ---
- NOTE: Patients with known T315I mutation status should receive ponatinib treatment - For patients under age 70, intended chemotherapy regimen must have been determined prior to randomization - STEP 3: REGISTRATION (RE-INDUCTION) - ELIGIBILITY CRITERIA - INCLUSION - Institution has received centralized MRD results confirming positive status - Patients who presented with acute organ dysfunction must have their total bilirubin and AST (SGOT)/ALT (SGPT) reduce to < 2 X institutional ULN - Patients who presented with acute organ dysfunction must have an estimated creatinine clearance > 45 mg/min (based on Cockcroft-Gault equation) - Investigators must confirm which TKI patient is to receive - NOTE: Patients with known T315I mutation status should receive ponatinib treatment - For patients under age 70 and previously assigned to Arm C, intended chemotherapy regimen must have been determined Exclusion Criteria: - PREREGISTRATION (STEP 0) ELIGIBILITY CRITERIA - EXCLUSION - Patient must not have received chemotherapy for B-ALL. --- T315I ---
- NOTE: Patients with known T315I mutation status should receive ponatinib treatment - For patients under age 70, intended chemotherapy regimen must have been determined prior to randomization - STEP 3: REGISTRATION (RE-INDUCTION) - ELIGIBILITY CRITERIA - INCLUSION - Institution has received centralized MRD results confirming positive status - Patients who presented with acute organ dysfunction must have their total bilirubin and AST (SGOT)/ALT (SGPT) reduce to < 2 X institutional ULN - Patients who presented with acute organ dysfunction must have an estimated creatinine clearance > 45 mg/min (based on Cockcroft-Gault equation) - Investigators must confirm which TKI patient is to receive - NOTE: Patients with known T315I mutation status should receive ponatinib treatment - For patients under age 70 and previously assigned to Arm C, intended chemotherapy regimen must have been determined Exclusion Criteria: - PREREGISTRATION (STEP 0) ELIGIBILITY CRITERIA - EXCLUSION - Patient must not have received chemotherapy for B-ALL. --- T315I --- --- T315I ---