EXTRAMEDULLARY RELAPSE AND OCCULT BONE MARROW INVOLVEMENT IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA: A PHASE III GROUP-WIDE STUDY
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.
Interventional
Primary Purpose: Treatment
Michael L.N. Willoughby, MD
Study Chair
Princess Margaret Hospital for Children
United States: Federal Government
CDR0000064968
NCT00002816
December 1996
Name | Location |
---|---|
Fred Hutchinson Cancer Research Center | Seattle, Washington 98109 |
Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
University of Michigan Comprehensive Cancer Center | Ann Arbor, Michigan 48109-0752 |
Kaplan Cancer Center | New York, New York 10016 |
Children's Hospital of Philadelphia | Philadelphia, Pennsylvania 19104 |
Mayo Clinic Cancer Center | Rochester, Minnesota 55905 |
Jonsson Comprehensive Cancer Center, UCLA | Los Angeles, California 90095-1781 |
University of Chicago Cancer Research Center | Chicago, Illinois 60637 |
Indiana University Cancer Center | Indianapolis, Indiana 46202-5265 |
University of Iowa Hospitals and Clinics | Iowa City, Iowa 52242 |
University of Minnesota Cancer Center | Minneapolis, Minnesota 55455 |
Lineberger Comprehensive Cancer Center, UNC | Chapel Hill, North Carolina 27599-7295 |
Ireland Cancer Center | Cleveland, Ohio 44106-5065 |
UCSF Cancer Center and Cancer Research Institute | San Francisco, California 94115-0128 |
Vanderbilt Cancer Center | Nashville, Tennessee 37232-6838 |
Huntsman Cancer Institute | Salt Lake City, Utah 84112 |
University of Wisconsin Comprehensive Cancer Center | Madison, Wisconsin 53792 |
Herbert Irving Comprehensive Cancer Center | New York, New York 10032 |
University of Nebraska Medical Center | Omaha, Nebraska 68198-3330 |
Long Beach Memorial Medical Center | Long Beach, California 90806 |
Children's Hospital Los Angeles | Los Angeles, California 90027-0700 |
Children's Hospital of Orange County | Orange, California 92668 |
Children's Hospital of Denver | Denver, Colorado 80218 |
Children's National Medical Center | Washington, District of Columbia 20010-2970 |
Children's Hospital Medical Center - Cincinnati | Cincinnati, Ohio 45229-3039 |
Children's Hospital of Columbus | Columbus, Ohio 43205-2696 |
Doernbecher Children's Hospital | Portland, Oregon 97201-3098 |
Children's Hospital of Pittsburgh | Pittsburgh, Pennsylvania 15213 |
Children's Hospital and Regional Medical Center - Seattle | Seattle, Washington 98105 |
Children's Mercy Hospital - Kansas City | Kansas City, Missouri 64108 |