Treatment of Childhood Acute Lymphoblastic Leukemia

This study has been terminated.
(Terminated by IRB for continuing review)
Sponsor:
Collaborator:
Children's Hospital Boston
Information provided by:
Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00165087
First received: September 9, 2005
Last updated: December 20, 2007
Last verified: December 2007
  Purpose

The purpose of this study is to reduce the side-effects and discomfort of anti-leukemia therapy, to attain long-term control of the disease and to hopefully eradicate it.


Condition Intervention Phase
Acute Lymphoblastic Leukemia
Drug: asparaginase (E. Coli)
Drug: asparaginase (Erwina)
Drug: dexrazoxane
Drug: doxorubicin
Procedure: cranial radiation (once daily fractionation)
Procedure: cranial radiation (twice-daily fractionation)
Procedure: Intrathecal chemotherapy without radiation
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 Childhood Acute Lymphoblastic Leukemia

Resource links provided by NLM:


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

Primary Outcome Measures:
  • -To evaluate the efficacy and safety of doxorubicin with or without dexrazoxane
  • -To determine the efficacy of hyperfractionated radiation plus standard intrathecal chemotherapy compared with intensive intrathecal chemotherapy alone in standard risk patients.
  • -To compare the relative efficacy and toxicity of E.coli and Erwinia asparaginase
  • -To compare the relative efficacy and toxicity of cranial radiation delivered in once-daily versus twice-daily fractions in high risk patinets.

Secondary Outcome Measures:
  • -To compare randomized treatment groups using health-related quality of life analyses.

Estimated Enrollment: 491
Study Start Date: January 1996
Study Completion Date: September 2006
Primary Completion Date: September 2006 (Final data collection date for primary outcome measure)
Detailed Description:
  • Children with acute lymphoblastic leukemia (ALL) are treated somewhat differently depending upon on the relative risk of the leukemia recurring. For this study they are classified into "Standard Risk", "High Risk" and "Infant/High Risk".
  • The treatment for patients in the "Standard Risk" and "High Risk" groups consists of three phases of therapy: induction treatment; prevention of brain and spinal cord leukemia (CNS treatment); and intensification/continuation chemotherapy.
  • The treatment for patients in the "Infant/High Risk" group consists of four phases of therapy: induction treatment; infant intensification therapy; intensification/continuation chemotherapy; and CNS treatment.
  • The induction treatment consists of a combination of chemotherapy drugs whose purpose is to kill all detectable leukemia cells. This process usually requires a least one month and includes six anti-leukemia drugs. These drugs are: vincristine, doxorubicin, methotrexate, cytosine arabinoside, asparaginase and steroids (methylprednisolone or prednisone).
  • After the induction phase, "Infant/High Risk" patients will receive a highly intensive month of treatment (infant intensification) . Drugs used during this month include high-dose methotrexate, asparaginase, 6-mercaptopurine and high dose cytosine arabinoside (ARA-C).
  • CNS treatment begins during induction therapy but is intensified during the second and third month after diagnosis. Treatment for all patients will include a series of spinal taps with the instillation of anti-leukemia drugs, including cytosine arabinoside and methotrexate and with or without hydrocortisone (depending upon randomization).
  • All high risk patients (those in both "High Risk" and "Infant/High Risk") as well as some standard risk patients will receive radiation treatment to the brain. Radiation therapy will either be given in either "conventional" treatments (once daily for 10 days), or "hyperfractionated" treatments (twice daily at half doses for 10 days). Total dose of radiation is 1800 cGy.
  • Intensification and continuation therapy, begins 4-5 weeks after diagnosis for "Standard Risk" and "High Risk" groups and 4-5 weeks after infant intensification in "Infant/High Risk" group. This phase of treatment continues until the completion of two years of treatment. Patients in the "Standard Risk" group will receive five anti-leukemia drugs (vincristine, prednisone, methotrexate, asparaginase, and 6-mercaptopurine). Patients in "High Risk" and "Infant/High Risk" will receive six anti-leukemia drugs (vincristine, prednisone, doxorubicin, methotrexate, asparaginase and 6-mercaptopurine).
  • All patients will be able to participate in a randomization comparing two types of asparaginase, E.coli and Erwinia. Patients will be randomized to receive either once weekly E.coli or once-weekly Erwinia during the Intensification phase, each given for a total of 20 weeks.
  • Patients in the "Standard Risk" group are able to participate in an additional randomization. Standard risk patients will be randomized to receive one of two different regimens designed to prevent central nervous system leukemia, either 1)radiation therapy (given twice daily) with chemotherapy in the spinal fluid every 18 weeks, or 2) intensive chemotherapy in the spinal fluid alone without radiation.
  • Patients in the "High Risk" and "Infant/High Risk" groups are able to participate in two randomizations in addition to the asparaginase randomization. The first will be to assess whether the drug dexrazoxane prevents heart damage caused by doxorubicin without affecting risk of relapse. Patients will be randomized to receive either doxorubicin alone or doxorubicin with dexrazoxane during the induction, CNS and intensification phases. The second randomization will compare the relative efficacy and toxicity of different cranial radiation schedules. Patients will be randomized to receive radiation in either once daily or twice daily fractions.
  • Blood and bone marrow samples will be collected to learn more about the biology of leukemia. These samples will also be used to test minimal residual disease levels to learn if these levels help predict risk of relapse.
  • Quality of life questionnaires will also be performed by the parents of patients, by children over eight, and by the child's clinician.
  Eligibility

Ages Eligible for Study:   up to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Acute lymphoblastic leukemia, excluding known mature B-cell ALL
  • < 18 years of age
  • Patients who are leukopheresed or exchanged are eligible for study only after completion of the pheresis or exchange transfusion
  • Absence of a t(8,14) (q24; q32), t (8,22), t(2,8)
  • Total bilirubin < 1.4mg/dl

Exclusion Criteria:

  • Known HIV positive
  • Prior steroid therapy within 30 days of diagnosis
  • Septic shock
  • Ongoing intracranial hemorrhage
  • Clinical evidence of CNS or lung leukostasis
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00165087

Locations
United States, Louisiana
Ochsner Clinic
New Orleans, Louisiana, United States, 70121
United States, Maine
Maine Medical Center
Lewiston, Maine, United States, 04240
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
United States, New York
Mt. Sinai Medical Center
New York, New York, United States, 10029
University of Rochester
Rochester, New York, United States, 14627
Canada, Ontario
McMaster University
Hamilton, Ontario, Canada
Canada, Quebec
Sainte Justine Hosptial
Montreal, Quebec, Canada
Laval University
Montreal, Quebec, Canada
Puerto Rico
San Jorge Children's Hospital
Santurce, Puerto Rico, 00912
Sponsors and Collaborators
Dana-Farber Cancer Institute
Children's Hospital Boston
Investigators
Principal Investigator: Stephen E. Sallan, MD Dana-Farber Cancer Institute
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00165087     History of Changes
Other Study ID Numbers: 95-001
Study First Received: September 9, 2005
Last Updated: December 20, 2007
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
childhood ALL
standard risk
high risk
infant/high risk

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Asparaginase
Doxorubicin
Razoxane
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Cardiovascular Agents
Chelating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 16, 2014