Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Treatment of Acute Lymphoblastic Leukemia in Children

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00400946
First received: November 16, 2006
Last updated: May 31, 2013
Last verified: May 2013
  Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving giving more than one drug (combination chemotherapy) may kill more cancer cells. It is not yet known whether pegasparaginase is more effective than asparaginase when given together with combination chemotherapy in treating acute lymphoblastic leukemia.

PURPOSE: This randomized phase III trial is studying pegasparaginase to see how well it works compared with asparaginase when given together with combination chemotherapy in treating young patients with newly diagnosed acute lymphoblastic leukemia.


Condition Intervention Phase
Drug/Agent Toxicity by Tissue/Organ
Leukemia
Drug: asparaginase
Drug: cyclophosphamide
Drug: cytarabine
Drug: dexamethasone
Drug: dexrazoxane hydrochloride
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: leucovorin calcium
Drug: mercaptopurine
Drug: methotrexate
Drug: methylprednisolone
Drug: pegaspargase
Drug: prednisolone
Drug: therapeutic hydrocortisone
Drug: vincristine sulfate
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of Acute Lymphoblastic Leukemia in Children

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Toxicity of pegasparaginase vs E. coli asparaginase [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Efficacy of pegasparaginase vs E. coli asparaginase [ Designated as safety issue: No ]
  • Prognostic significance of asparaginase antibody formation [ Designated as safety issue: No ]
  • Correlation of trough enzyme levels with outcome (toxicity and relapse) [ Designated as safety issue: Yes ]
  • Quality of life [ Designated as safety issue: No ]
  • Comparison of trough serum asparaginase enzyme levels, asparagine levels, and anti-asparaginase antibody levels [ Designated as safety issue: No ]
  • Rate of infections (episodes of bacteremia and disseminated fungal infections) during the remission induction phase of combination chemotherapy [ Designated as safety issue: No ]
  • Prognostic significance of response to remission induction chemotherapy as measured by morphology and minimal residual disease (MRD) [ Designated as safety issue: No ]
  • Outcome based on MRD status after 28 days of multiagent chemotherapy that intensifies treatment for B-lineage patients with MRD levels > 0.001 at the end of remission induction therapy [ Designated as safety issue: No ]
  • Outcome based on MRD status after 14 days of multiagent chemotherapy, every 18 weeks after achieving complete remission, and at the completion of all chemotherapy [ Designated as safety issue: No ]
  • Comparison of the outcome of patients (based on bone marrow morphology after 14 days of multiagent chemotherapy) with M2/M3 status vs M1 status or hypoplastic marrows [ Designated as safety issue: No ]
  • Efficacy of CNS-directed treatment [ Designated as safety issue: No ]
  • CNS-related toxicity of CNS-directed treatment [ Designated as safety issue: Yes ]
  • Relationship between dietary intake and rate of infections and risk of development of fractures during treatment [ Designated as safety issue: No ]

Estimated Enrollment: 800
Study Start Date: April 2005
Estimated Study Completion Date: November 2013
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I
Patients receive combination chemotherapy intrathecally, by infusion, by mouth, and by injection for up to approximately 2 years. They also receive E. coli asparaginase intramuscularly. Some patients also undergo radiation therapy to the head once a day for 8 or 10 days.
Drug: asparaginase
Given intramuscularly
Drug: cyclophosphamide
Given IV
Drug: cytarabine
Given IV and intrathecally
Drug: dexamethasone
Given orally
Drug: dexrazoxane hydrochloride
Given IV
Drug: doxorubicin hydrochloride
Given IV
Drug: etoposide
Given IV
Drug: leucovorin calcium
Given IV
Drug: mercaptopurine
Given orally
Drug: methotrexate
Given IV, intrathecally, and intramuscularly
Drug: methylprednisolone
Given IV
Drug: prednisolone
Given orally
Drug: therapeutic hydrocortisone
Given intrathecally
Drug: vincristine sulfate
Given IV
Radiation: radiation therapy
Some patients may undergo cranial radiotherapy
Experimental: Arm II
Patients receive combination chemotherapy intrathecally, by infusion, by mouth, and by injection for up to approximately 2 years. They also receive pegasparaginase IV. Some patients also undergo radiation therapy to the head once a day for 8 or 10 days.
Drug: cyclophosphamide
Given IV
Drug: cytarabine
Given IV and intrathecally
Drug: dexamethasone
Given orally
Drug: dexrazoxane hydrochloride
Given IV
Drug: doxorubicin hydrochloride
Given IV
Drug: etoposide
Given IV
Drug: leucovorin calcium
Given IV
Drug: mercaptopurine
Given orally
Drug: methotrexate
Given IV, intrathecally, and intramuscularly
Drug: methylprednisolone
Given IV
Drug: pegaspargase
Given IV
Drug: prednisolone
Given orally
Drug: therapeutic hydrocortisone
Given intrathecally
Drug: vincristine sulfate
Given IV
Radiation: radiation therapy
Some patients may undergo cranial radiotherapy

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   1 Year to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of acute lymphoblastic leukemia (ALL)

    • No known mature B-cell ALL, defined by the presence of any of the following:

      • Surface immunoglobulin
      • L3 morphology
      • t(8;14)(q24;q32)
      • t(8;22)
      • t(2;8)
    • T-cell surface markers and t(8;14)(q24;q11) allowed
  • Meets criteria for 1 of the following risk groups:

    • Standard-risk (SR) disease, defined by the following criteria:

      • 1 to 9 years of age
      • Highest pretreatment WBC < 50,000/mm³
      • No evidence of CNS leukemia, defined by all of the following:

        • Diagnostic lumbar puncture without any cerebrospinal fluid (CSF) blast cells on cytospin (CNS-1) OR < 5 WBC/high-power field (hpf) in CSF with blast cells on cytospin (CNS-2)
        • CNS-1 CSF on days 18 and 32 of study treatment
        • Absence of cranial nerve palsy at diagnosis
      • Absence of T-cell markers on lymphoblasts
      • Absence of t(9;22), mixed-lineage leukemia (MLL) gene translocations, and hypodiploidy < 45 chromosomes by karyotype or fluorescent in situ hybridization (FISH)
      • Minimal residual disease (MRD) level < 0.001 at the end of study remission induction therapy (day 32) OR end-of-induction MRD status cannot be determined
    • High-risk (HR) disease, defined by any of the following criteria:

      • 10 to 17 years of age
      • Highest pretreatment WBC ≥ 50,000/mm³
      • Evidence of CNS leukemia, defined by any of the following:

        • Diagnostic lumbar puncture with ≥ 5 WBC/hpf and blast cells on cytospin (CNS-3)
        • CNS-2 CSF on day 18 or 32 of study treatment
        • CNS-3 CSF on day 18 of study treatment
        • Presence of cranial nerve palsy at diagnosis
      • Predominance of T-cell markers on lymphoblasts
      • Presence of t(9;22)

        • An allogeneic stem cell donor will be sought for transplantation
        • These patients will not receive CNS therapy during study treatment
      • B-lineage and MRD level < 0.001 at the end of study remission induction therapy (day 32) OR end-of-induction MRD status cannot be determined
    • Very high-risk (VHR) disease, defined by any of the following criteria:

      • Presence of MLL gene translocations (i.e., t[4;11]) by karyotype, FISH, or molecular analysis
      • Presence of hypodiploidy < 45 chromosomes by karyotype or FISH analysis
      • MRD level ≥ 0.001 at the end of study remission induction therapy (day 32)
  • No secondary ALL

PATIENT CHARACTERISTICS:

  • No known HIV positivity
  • Not pregnant or nursing
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

  • No prior therapy except steroids of ≤ 1 week in duration and/or emergent radiation therapy to the mediastinum

    • Patients treated with steroids within the past 7 days will not receive steroid prophase during study treatment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00400946

Locations
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, New York
Albert Einstein Cancer Center at Albert Einstein College of Medicine
Bronx, New York, United States, 10461
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
New York, New York, United States, 10032
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, Rhode Island
Hasbro Children's Hospital
Providence, Rhode Island, United States, 02903
United States, Virginia
INOVA Fairfax Hospital
Fairfax, Virginia, United States, 22031
Canada, Ontario
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8N 3Z5
Canada, Quebec
Hopital Sainte Justine
Montreal, Quebec, Canada, H3T 1C5
Centre de Recherche du Centre Hospitalier de l'Universite Laval
Sainte Foy, Quebec, Canada, GIV 4G2
Puerto Rico
San Jorge Children's Hospital
Santurce, Puerto Rico, 00912
Sponsors and Collaborators
Dana-Farber Cancer Institute
Investigators
Principal Investigator: Lewis B. Silverman, MD Dana-Farber Cancer Institute
  More Information

Additional Information:
Publications:
Responsible Party: Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00400946     History of Changes
Obsolete Identifiers: NCT00165165
Other Study ID Numbers: 05-001 / CDR0000513019, P01CA068484, P30CA006516, DFCI-05001
Study First Received: November 16, 2006
Last Updated: May 31, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:
drug/agent toxicity by tissue/organ
untreated childhood acute lymphoblastic leukemia
L1 childhood acute lymphoblastic leukemia
L2 childhood acute lymphoblastic leukemia
T-cell childhood acute lymphoblastic leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Asparaginase
Cortisol succinate
Cyclophosphamide
Dexamethasone
Dexrazoxane
Doxorubicin
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone-17-butyrate
Levoleucovorin
Liposomal doxorubicin
Methotrexate
Methylprednisolone
Methylprednisolone Hemisuccinate
Methylprednisolone acetate
Pegaspargase
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate

ClinicalTrials.gov processed this record on November 25, 2014