Treatment of Newly Diagnosed High Risk Acute Lymphoblastic Leukemia in Children

January 15, 2015 updated by: Hee Young Shin, The Korean Society of Pediatric Hematology Oncology
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Anticipated)

110

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Seoul, Korea, Republic of
        • Recruiting
        • Seoul National University, College of Medicine
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Rapid early responder group
  1. RER Consolidation BM exam on day 63: M1, M2 -> IM M3 or residual CNS ds or Bx proven extramedullary ds - off protocol
  2. RER Interim Maintenance #1
  3. RER Delayed Intensification
  4. RER Interim Maintenance #2
  5. RER Maintenance (12 weeks=84 days)
Experimental: Slow early responder group

Includes : SER, Testis(+), CNS 3, T-cell (non ETP), Initial PB WBC ≥ 100,000/μL

1. SER Consolidation

  • Intrathecal triple chemotherapy at d0, 7, 14, 21 2. SER Interim Maintenance #1
  • high dose methotrexate included
  • Intrathecal triple chemotherapy at d0, 28 3. SER Delayed Intensification #1
  • Intrathecal triple chemotherapy at d0, 28, 35 4. SER Interim Maintenance #2
  • high dose methotrexate included
  • Intrathecal triple chemotherapy at d0, 28 5. SER Delayed Intensification #2
  • Intrathecal triple chemotherapy at d0, 28, 35 6. SER Maintenance
  • Intrathecal triple chemotherapy at d0
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
Drug: Intrathecal triple chemotherapy
Intrathecal triple chemotherapy for SEG group instead of radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
event-free survival of SER group
Time Frame: 5 years from diagnosis
5 years from diagnosis

Secondary Outcome Measures

Outcome Measure
Time Frame
Number of adverse events
Time Frame: 5 years from diagnosis
5 years from diagnosis

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Korean Society of Pediatric Hematology Oncology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2015

Primary Completion (Anticipated)

April 1, 2023

Study Completion (Anticipated)

April 1, 2023

Study Registration Dates

First Submitted

January 12, 2015

First Submitted That Met QC Criteria

January 12, 2015

First Posted (Estimate)

January 15, 2015

Study Record Updates

Last Update Posted (Estimate)

January 16, 2015

Last Update Submitted That Met QC Criteria

January 15, 2015

Last Verified

January 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KSPHO_HRALL

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Child

Clinical Trials on high dose methotrexate

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Ecuador

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe