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Treatment of Newly Diagnosed High Risk Acute Lymphoblastic Leukemia in Children

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ClinicalTrials.gov Identifier: NCT02339350
Recruitment Status : Recruiting
First Posted : January 15, 2015
Last Update Posted : January 16, 2015
Sponsor:
Information provided by (Responsible Party):
Hee Young Shin, The Korean Society of Pediatric Hematology Oncology

Brief 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.

Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia Child Drug: high dose methotrexate Drug: Intrathecal triple chemotherapy Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Newly Diagnosed High Risk Acute Lymphoblastic Leukemia in Children
Study Start Date : January 2015
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : April 2023


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




Primary Outcome Measures :
  1. event-free survival of SER group [ Time Frame: 5 years from diagnosis ]

Secondary Outcome Measures :
  1. Number of adverse events [ Time Frame: 5 years from diagnosis ]


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Ages Eligible for Study:   1 Year to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02339350


Locations
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Korea, Republic of
Seoul National University, College of Medicine Recruiting
Seoul, Korea, Republic of
Contact: Hee Young Shin, MD, PhD    82-2-2072-2917    hyshin@snu.ac.kr   
Sponsors and Collaborators
The Korean Society of Pediatric Hematology Oncology
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Responsible Party: Hee Young Shin, KSPHO, The Korean Society of Pediatric Hematology Oncology
ClinicalTrials.gov Identifier: NCT02339350    
Other Study ID Numbers: KSPHO_HRALL
First Posted: January 15, 2015    Key Record Dates
Last Update Posted: January 16, 2015
Last Verified: January 2015
Additional relevant MeSH terms:
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Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors