Treatment of Newly Diagnosed High Risk Pediatric Acute Lymphoblastic Leukemia (HR ALL)

Jae Wook Lee

Status and phase: Enrolling; Phase 2

Conditions: Pediatric Acute Lymphoblastic Leukemia

Treatments: Drug: ALL, High risk

Study type: Interventional

Funder types: Other

Identifiers

NCT06184009

2023-3626-0001

Details and patient eligibility

About

• Clinical and genetic factors consistent with High risk : Induction → Consolidation

  1. BM MRD < 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
  <!-- -->

  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.

Full 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
  <!-- -->

  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.

Enrollment: 370 estimated patients

Sex: All

Ages: 1 to 19 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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370 participants in 1 patient group

ALL, High risk with DI #2(Doxorubicin)

Experimental group

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 <!-- --> 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 : Continue with \&#39;No. 2\&#39; of High risk regimen starting with DI #1 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.

Treatment:

Drug: ALL, High risk