Combination Chemotherapy in Treating Children With Relapsed Acute Lymphoblastic Leukemia
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Leukemia
Intervention: cytarabine (Drug); dexamethasone (Drug); etoposide (Drug); idarubicin (Drug); ifosfamide (Drug); leucovorin calcium (Drug); mesna (Drug); methotrexate (Drug); pegaspargase (Drug); therapeutic hydrocortisone (Drug); thioguanine (Drug); vincristine (Drug); low-LET cobalt-60 gamma ray therapy (Procedure); low-LET electron therapy (Procedure); low-LET photon therapy (Procedure)
Phase: Phase 3
Status: Active, not recruiting
Sponsored by: Children's Cancer Group Official(s) and/or principal investigator(s):
Michael L.N. Willoughby, MD, Study Chair, Affiliation: Princess Margaret Hospital for Children
Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing
so they stop growing or die.
PURPOSE: Phase III trial to compare the effectiveness of combination chemotherapy in treating
children who have relapsed acute lymphoblastic leukemia.
Clinical Details
Official title: EXTRAMEDULLARY RELAPSE AND OCCULT BONE MARROW INVOLVEMENT IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA: A PHASE III GROUP-WIDE STUDY
Study design: Treatment
Detailed description:
OBJECTIVES: I. Improve the outcome in children with first isolated central nervous system
(CNS), testicular, or ocular relapse of acute lymphoblastic lymphoma (ALL), and increase the
knowledge of the characteristics of extramedullary and subsequent relapses of ALL. II.
Quantitate, by current molecular biologic techniques, occult systemic leukemia in cases of
conventional isolated extramedullary relapse, and examine the relationship between this
assessment and subsequent clinical outcome, particularly overt marrow relapse. III.
Quantitate occult systemic leukemia in subsets of extramedullary relapse that include site
(CNS, testis, or eye), time of relapse (early or late), initial risk group, immunophenotype,
DNA index and karyotype, gender (for CNS and eye), and ethnicity, and assess the response to
therapy in patients entered on companion protocol CCG-B958. IV. Compare the relative
sensitivities of two quantitative in vitro assays for occult systemic leukemia
(fluorescence-activated cell sorter/leukemic progenitor cell clonogenic assay vs. polymerase
chain reaction-based clonospecific assay), correlate the assays with clinical outcome, and
assess other biologic studies of leukemic cells (e. g., neurotropic potential in the SCID
mouse xenograft model and methotrexate sensitivity). V. Determine the event-free survival
(EFS) and pattern of failure in children with first isolated CNS, testicular, or ocular
relapse after treatment that includes intensive systemic chemotherapy. VI. Correlate EFS in
patients with CNS and ocular relapse with sex, and in patients with relapse at all three
sites with ethnicity. VII. Evaluate the impact of combined chemotherapy and radiotherapy on
health status in survivors at two and four years after extramedullary relapse and study
entry.
OUTLINE: All patients receive induction chemotherapy over 5 weeks with: etoposide,
ifosfamide/mesna, dexamethasone, vincristine, and pegaspargase (if pegaspargase is not
available, E. coli asparaginase may be substituted throughout study); then dexamethasone,
vincristine, pegaspargase (or E. coli asparaginase), and high-dose methotrexate with
leucovorin rescue; and triple intrathecal chemotherapy (TIT). Following induction
chemotherapy, all patients receive two 6-week courses of intensification therapy with
intermittent TIT; each course consists of dexamethasone, vincristine, high-dose
methotrexate/leucovorin, thioguanine, cytarabine, etoposide, and pegaspargase (or E. coli
asparaginase) followed by dexamethasone, vincristine, high-dose methotrexate/leucovorin,
thioguanine, ifosfamide/mesna, and idarubicin. Patients receive 2 additional courses of
intensification chemotherapy followed by four 12-week courses of maintenance chemotherapy
with vincristine and methotrexate every 2 weeks and daily oral thioguanine. Total duration of
therapy is 78 weeks. Patients with isolated ocular relapse receive local radiotherapy prior
to initiation of induction chemotherapy; those who also have CNS leukemia begin TIT with the
radiotherapy. Patients with CNS relapse receive craniospinal irradiation during the first
month of maintenance therapy, with the dose and fields based on whether they will receive TBI
and whether they have had CNS irradiation previously. Patients with testicular relapse
receive bilateral testicular irradiation during the first 3 weeks of intensification therapy.
Patients are followed every 3 months for 3 years, every 6 months for 3 years, and yearly
thereafter, or upon relapse, second malignancy, loss to follow up, or death. All patients
undergo quality-of-life assessment at entry and 2 and 4 years after entry.
PROJECTED ACCRUAL: Approximately 120 patients will be accrued for this study.
Eligibility
Minimum age: N/A.
Maximum age: 20 Years.
Gender(s): Both.
Criteria:
DISEASE CHARACTERISTICS: Acute lymphoblastic leukemia (ALL) with isolated extramedullary
relapse Relapse occurred during or following front-line therapy for ALL Initial diagnosis
of more than 25% blasts of L1 or L2 morphology No leukemic marrow (M1) by conventional
assessment Patients with B precursor ALL must also be enrolled on study CCG-B958 Relapse
occurred in the CNS, testis, or eye Ocular relapse confirmed by an ophthalmologist and by
cytology or iris biopsy Combined CNS and ocular relapse eligible Down Syndrome patients not
eligible No prior bone marrow transplantation in first remission No prior toxicity from any
study drugs Patient age: Under 21
PATIENT CHARACTERISTICS: See General Eligibility Criteria
Locations and Contacts
British Columbia Children's Hospital, Vancouver, British Columbia V6H 3V4, Canada
Children's Hospital Los Angeles, Los Angeles, California 90027-0700, United States
Children's Hospital of Orange County, Orange, California 92668, United States
Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California 90095-1781, United States
Long Beach Memorial Medical Center, Long Beach, California 90806, United States
UCSF Cancer Center and Cancer Research Institute, San Francisco, California 94115-0128, United States
Children's Hospital of Denver, Denver, Colorado 80218, United States
Children's National Medical Center, Washington, District of Columbia 20010-2970, United States
University of Chicago Cancer Research Center, Chicago, Illinois 60637, United States
Indiana University Cancer Center, Indianapolis, Indiana 46202-5265, United States
University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, United States
University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48109-0752, United States
Mayo Clinic Cancer Center, Rochester, Minnesota 55905, United States
University of Minnesota Cancer Center, Minneapolis, Minnesota 55455, United States
Children's Mercy Hospital - Kansas City, Kansas City, Missouri 64108, United States
University of Nebraska Medical Center, Omaha, Nebraska 68198-3330, United States
Herbert Irving Comprehensive Cancer Center, New York, New York 10032, United States
Kaplan Cancer Center, New York, New York 10016, United States
Memorial Sloan-Kettering Cancer Center, New York, New York 10021, United States
Lineberger Comprehensive Cancer Center, UNC, Chapel Hill, North Carolina 27599-7295, United States
IWK Grace Health Centre, Halifax, Nova Scotia B3J 3G9, Canada
Children's Hospital Medical Center - Cincinnati, Cincinnati, Ohio 45229-3039, United States
Children's Hospital of Columbus, Columbus, Ohio 43205-2696, United States
Ireland Cancer Center, Cleveland, Ohio 44106-5065, United States
Doernbecher Children's Hospital, Portland, Oregon 97201-3098, United States
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States
Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States
Vanderbilt Cancer Center, Nashville, Tennessee 37232-6838, United States
Huntsman Cancer Institute, Salt Lake City, Utah 84132, United States
Children's Hospital and Regional Medical Center - Seattle, Seattle, Washington 98105, United States
Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, United States
Princess Margaret Hospital for Children, Perth, Western Australia 6001, Australia
University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin 53792, United States
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: December 1996
Last updated: May 23, 2008
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