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EXTRAMEDULLARY RELAPSE AND OCCULT BONE MARROW INVOLVEMENT IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA: A PHASE III GROUP-WIDE STUDY


Phase 3
N/A
20 Years
Open (Enrolling)
Both
Leukemia

Thank you

Trial Information

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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Michael L.N. Willoughby, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Princess Margaret Hospital for Children

Authority:

United States: Federal Government

Study ID:

CDR0000064968

NCT ID:

NCT00002816

Start Date:

December 1996

Completion Date:

Related Keywords:

  • Leukemia
  • recurrent childhood acute lymphoblastic leukemia
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma

Name

Location

Fred Hutchinson Cancer Research CenterSeattle, Washington  98109
Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
University of Michigan Comprehensive Cancer CenterAnn Arbor, Michigan  48109-0752
Kaplan Cancer CenterNew York, New York  10016
Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
Mayo Clinic Cancer CenterRochester, Minnesota  55905
Jonsson Comprehensive Cancer Center, UCLALos Angeles, California  90095-1781
University of Chicago Cancer Research CenterChicago, Illinois  60637
Indiana University Cancer CenterIndianapolis, Indiana  46202-5265
University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
University of Minnesota Cancer CenterMinneapolis, Minnesota  55455
Lineberger Comprehensive Cancer Center, UNCChapel Hill, North Carolina  27599-7295
Ireland Cancer CenterCleveland, Ohio  44106-5065
UCSF Cancer Center and Cancer Research InstituteSan Francisco, California  94115-0128
Vanderbilt Cancer CenterNashville, Tennessee  37232-6838
Huntsman Cancer InstituteSalt Lake City, Utah  84112
University of Wisconsin Comprehensive Cancer CenterMadison, Wisconsin  53792
Herbert Irving Comprehensive Cancer CenterNew York, New York  10032
University of Nebraska Medical CenterOmaha, Nebraska  68198-3330
Long Beach Memorial Medical CenterLong Beach, California  90806
Children's Hospital Los AngelesLos Angeles, California  90027-0700
Children's Hospital of Orange CountyOrange, California  92668
Children's Hospital of DenverDenver, Colorado  80218
Children's National Medical CenterWashington, District of Columbia  20010-2970
Children's Hospital Medical Center - CincinnatiCincinnati, Ohio  45229-3039
Children's Hospital of ColumbusColumbus, Ohio  43205-2696
Doernbecher Children's HospitalPortland, Oregon  97201-3098
Children's Hospital of PittsburghPittsburgh, Pennsylvania  15213
Children's Hospital and Regional Medical Center - SeattleSeattle, Washington  98105
Children's Mercy Hospital - Kansas CityKansas City, Missouri  64108