Newly-diagnosed Intermediate/High Risk Pediatric B-cell ALL Protocol

Condition(s) studied

Investigational drug(s) / intervention(s)

Blinatumomab (Group A): For Group A I/HR-ALL patients after induction remission phase, continuous 28 days' blinatumomab followed by 3 cycles of high-dose methotrexate (HDMTX) will be applied, subsequently followed by interim continuation, late intensification, and maintenance therapy

Venetoclax (nonRand Group): For I/HR patients non eligible for blinatumomab randomization, venetoclax+ mini-hyperCVD will be applied after PVDL induction, subsequently followed by CAT as intensification, interim continuation, late intensification, and maintenance therapy

Blinatumomab (Group B): For Group B I/HR-ALL patients after induction remission phase: a two 14-day cycles of blinatumomab, alternating with three cycles of HDMTX will be applied, subsequently followed interim continuation, late intensification, and maintenance therapy

Study summary

Building upon the results from the CCCG-ALL-2015, CCCG-ALL-2020 multicenter study cohort, concurrent research findings, and the latest clinical trials, the CCCG-ALL-2025 I/HR-B-ALL is thus developed to further improve the event-free survival (EFS), and overall survival (OS), and quality of life (QoL) of children with intermediate- and high- risk B-cell childhood acute lymphoblastic leukaemia (I/HR-B-ALL), while decreasing adverse reactions and transplantation rates. This trial primarily aims to explore:

1. The efficacy of two randomized Blinatumomab application scheme on I/HR-ALL as determined by MRD negatvitiy rate.
2. The efficacy of modified mini-hyperCVD + Venetoclax in I/HR-ALL cannot afford blinatumomab, in contrast to historical control as determined by MRD negatvitiy rate.

Eligibility

Primary outcome measure(s)

• To investigate if Group B[2*(14-day blinatumomab + HDMTX*2)] can result in noninferior event-free survival (EFS) compared to Group A [28-day blinatumomab + HDMTX*4 — Based on the above analysis in this study the investigators will randomize 1800 patients. The analysis will start1.5 years after the last patient is randomized. The expected study duration is approximately 6.5 years.
  * The randomization is stratified by hospitals and status of flow-cytometry MRD (positive or negative) immediately prior to the blinatumomab-HDMTX treatment. * Kaplan-Meier (KM) estimates of each EFS function will be computed along with standard error by the default procedure in R. To test noninferiority the investigators consider a noninferiority margin of 0.04 for 5-year EFS as clinically meaningful. * Assume the EFS in the control group (Arm A) to be the same as the provisional I/HR in the CCCG-ALL2020 trial (preliminary data above), with the 1-year and 3-year EFS possibly 0.837 and 0.768 respectively. A simulation study with 10,000 rounds shows that by randomizing 1800 patients and 1.5 years of follow up, the above decision rule of declaring noninferiority has well controlled probabilities of false positive and false negative errors.

Trial sites (27)

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