Treatment of Newly Diagnosed High Risk Acute Lymphoblastic Leukemia in Children

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

Treatment of Newly Diagnosed High Risk Acute Lymphoblastic Leukemia in Children

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02339350
• Other study ID #: KSPHO_HRALL
• Status: Recruiting
• Phase: Phase 2
• First received: January 12, 2015
• Last updated: January 15, 2015
• Start date: January 2015
• Est. completion date: April 2023

Study information

• Verified date: January 2015
• Source: The Korean Society of Pediatric Hematology Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Ministry of Food and Drug Safety
• Study type: Interventional

Clinical Trial Summary

Treatment of pediatric acute lymphoblastic leukemia (ALL) has advanced and the overall survival exceeds 80% nowadays. However the overall survival of high risk ALL remains 75-90%, thus recent studies focus on treatment intensification according to the risk group. According to the previous reports, we designed a multicenter prospective trial for pediatric ALL.

Description:

Purpose of the study

1. For slow early responder (SER), to confirm if the augmented interim maintenance using intravenous high dose methotrexate will improve the treatment outcome.

2. For slow early responder (SER), to confirm if removal of prophylactic radiotherapy will relieve long term complications.

3. To predict the treatment response and prognosis high risk pediatric ALL by monitoring of minimal residual disease (MRD).

Inclusion criteria

1. Diagnosis

1. Newly diagnosed B-precursor ALL meeting criteria 1.2

2. Newly diagnosed B-precursor ALL who was previously treated with steroid.

3. Newly diagnosed T cell ALL, excluding early T-cell precursor (ETP) leukemia

1.2 Initial WBC count

1. from 1 years old to 9 years old : WBC ≥ 50,000/μL

2. from 10 years old to 21 years old : Any WBC

3. from 1 years old to 21 years old : Any WBC with Testicular leukemia or CNS leukemia (CNS3)

Exclusion criteria (who are classified as very high risk group) 2.1 Philadelphia chromosome (+) or bcr/abl rearrangement (+) 2.2 Chromosome <45 by cytogenetics 2.3 Induction failure (Day 28 M3 marrow (>25% blasts)) 2.4 t(4:11) (as identified by cytogenetics, FISH or molecular studies) 2.5 Early T-cell precursor leukemia 2.6 Down syndrome ALL

Methods We will classify the patients to rapid early responder (RER) and slow early responder (SER), according to the treatment response after induction remission and risk factors at diagnosis. SER includes M2 (5-25% or leukemic cells at bone marrow exam) or M3 (25% or more of leukemic cells at bone marrow exam) response at the 14th day of the start of induction remission. If a patient showed total WBC count ≥ 100,000/μL, had testis or CNS (CNS 3) involvement at diagnosis and was diagnosed as T-ALL, the patients will also be included into the SER group.

Rapid early responders will undergo interim maintenance two times and reinduction for one time. Slow early responders will undergo two times of interim maintenance treatment with high dose intravenous methotrexate. For SER, adriamycin was previously administered only when absolute neutrophil count and platelet was normal, but it will be administered without restriction in this study. Both groups (RER and SER) will undergo maintenance chemotherapy thereafter, with the treatment duration of 3 years from the 1st interim maintenance for boys and 2 years for girls.

For SER group, prophylactic radiotherapy will not be done and it will be replaced by high dose intravenous methotrexate and intensification of intrathecal chemotherapy by replacing the intrathecal methotrexate to intrathecal cytarabine, methotrexate and hydrocortisone.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 110
• Est. completion date: April 2023
• Est. primary completion date: April 2023
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 21 Years

Eligibility

Inclusion Criteria:

1. Diagnosis

1. Newly diagnosed B-precursor ALL meeting criteria 1.2

2. Newly diagnosed B-precursor ALL who was previously treated with steroid.

3. Newly diagnosed T cell ALL, excluding early T-cell precursor (ETP) leukemia

1.2 Initial WBC count

1. from 1 years old to 9 years old : WBC = 50,000/µL

2. from 10 years old to 21 years old : Any WBC

3. from 1 years old to 21 years old : Any WBC with Testicular leukemia or CNS leukemia (CNS3)

Exclusion Criteria:

1. Philadelphia chromosome (+) or bcr/abl rearrangement (+)

2. Chromosome <45 by cytogenetics

3. Induction failure (Day 28 M3 marrow (>25% blasts))

4. t(4:11) (as identified by cytogenetics, FISH or molecular studies)

5. Early T-cell precursor leukemia

6. Down syndrome ALL

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Child
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• high dose methotrexate
HD-MTX IV 5,000 mg/m2 I.V. over 4hr on day 0, 14, 28, 42 of SER interim maintenance schedule
• Intrathecal triple chemotherapy
Intrathecal triple chemotherapy for SEG group instead of radiotherapy

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University, College of Medicine	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
The Korean Society of Pediatric Hematology Oncology

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	event-free survival of SER group		5 years from diagnosis	No
Secondary	Number of adverse events		5 years from diagnosis	Yes