Clinical trial NCT06184009: Treatment of Newly Diagnosed High Risk Pediatric Acute Lymphoblastic Leukemia
Official title: Treatment of Newly Diagnosed High Risk Pediatric Acute Lymphoblastic Leukemia-prospective, Nationwide, Multi-center Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Pediatric Acute Lymphoblastic Leukemia
Keywords: HR ALL
NGS-MRD
Lead sponsor: Seoul St. Mary's Hospital
Sponsor class: OTHER
Collaborators: name: Samsung Medical Center
name: Asan Medical Center
name: Seoul National University Hospital
name: Severance Hospital
name: Pusan National University Yangsan Hospital
name: Korea University Anam Hospital
First posted: 2023-12-28
Enrollment: 370
Sex: ALL
Minimum age (years): 1
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: * Clinical and genetic factors consistent with High risk : Induction → Consolidation

  1. BM MRD \&lt; 0.01% : IM #1 → DI #1 → IM #2 → Maintenance
  2. BM MRD ≥ 0.01% : IM #1 → DI #1 → IM #2 → DI #2 → Maintenance
  3. BM MRD ≥ 0.01% after Consolidation

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  1. T cell ALL : Change to very high risk regimen
  2. Pre-B ALL : IM #1 → Intensification

     1. BM MRD \&lt; 0.01% after IM #1 : DI #1 → IM #2 → DI #2 → Maintenance
     2. BM MRD ≥ 0.01% after IM #1 : Change to Very high risk regimen

        * Difference in the number of \&#39;interim maintenance(IM)\&#39; and \&#39;delayed intensification(DI)\&#39; is important for chemotherapies based on MRD.

Detailed description: * Clinical and genetic factors consistent with High risk : Induction → Consolidation

  1. BM MRD \&lt; 0.01% after both Induction and Consolidation : IM #1 → DI #1 → IM #2 → Maintenance
  2. BM MRD ≥ 0.01% after Induction, \&lt; 0.01% after Consolidation : IM #1 → DI #1 → IM #2 → DI #2 → Maintenance
  3. BM MRD ≥ 0.01% after Consolidation

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  1. T cell ALL : Change to very high risk regimen
  2. Pre-B ALL : IM #1 → Intensification

     1. BM MRD \&lt; 0.01% after IM #1 : DI #1 → IM #2 → DI #2 → Maintenance
     2. BM MRD ≥ 0.01% after IM #1 : Change to Very high risk regimen

        * T cell ALL patients with M1 BM post-Consolidation will start IM #1. However, the patients will switch to Very high risk regimen at the next chemotherapy cycle once post-Consolidation MRD ≥ 0.01% has been reported.

Eligibility criteria: \<Inclusion Criteria\>

* Age: 1year\~19years of age at diagnosis
* Patients who are newly diagnosed Pre-B ALL and meet one of the following criteria

  * High-risk group according to the National Cancer Institute (NCI)/Rome: Age greater than or equal to 10 years and less than 19 years at diagnosis, or white blood cell count greater than or equal to 50 x 10\^9/L at diagnosis
  * If extra-bone marrow lesions are identified at the time of diagnosis, Central nervous system involvement (CNS3) or testicular involvement
  * High-risk gene variants:

KMT2A rearrangement intrachromosomal amplification of chromosome 21 (iAMP21)

● If subjects are under the age of 10 at the time of diagnosis and took steroids for more than 24 hours within two weeks before the diagnosis, the risk group will be determined by the presence of a whole blood test within three days before starting steroids. If a whole blood test is performed within three days before beginning steroids, the risk group will be assessed based on the white blood cell count in the test. If there is no whole blood test before starting steroids, subjects are classified as a high-risk group. If subjects are ten or older at diagnosis, pre-diagnosis steroid treatment will not affect the risk classification.

* Newly diagnosed T cell ALL

\<Exclusion Criteria\>

* Patients with Burkitt leukemia/lymphoma or mature B-cell leukemia
* Patients with Down syndrome
* potential of pregnancy or during pregnancy (patients of childbearing age need adequate contraception for the duration of the trial)
* Patients who have already received steroid treatment for newly diagnosed ALL specified in the above selection criteria or chemotherapies more than one intrathecal cytarabine treatment
* Participating in an interventional clinical trial other than this research

Primary outcomes:
measure: Event Free Survival
timeFrame: Up to 5 years
Secondary outcomes:
measure: Overall Survival
timeFrame: Up to 5 years
measure: Recurred rate
timeFrame: Up to 5 years
measure: Death rate related to infusion
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul saint Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Yangsan
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
Study officials:
affiliation: The Catholic University of Korea
name: Jae Wook Lee, Ph.D
role: STUDY_CHAIR
References: