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Combination Chemotherapy in Treating Children With Relapsed Acute Lymphoblastic Leukemia

Sponsor
Children's Oncology Group (Other)
Overall Status
Completed
CT.gov ID
NCT00002816
Collaborator
National Cancer Institute (NCI) (NIH)
120
Enrollment
33
Locations
2
Arms
112
Duration (Months)
3.6
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
120 participants
Primary Purpose:
Treatment
Official Title:
EXTRAMEDULLARY RELAPSE AND OCCULT BONE MARROW INVOLVEMENT IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA: A PHASE III GROUP-WIDE STUDY
Study Start Date :
Dec 1, 1996
Actual Primary Completion Date :
Nov 1, 2002
Actual Study Completion Date :
Apr 1, 2006

Arms and Interventions

Arm Intervention/Treatment
Experimental: EARLY # CNS RELAPSE with BM DONOR

Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, PEG, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, pegaspargase, Ifosfamide with Mesna) and Idarubicin and CXRT.

Drug: cytarabine
Given IV
Other Names:
  • Cytosine Arabinoside
  • Ara-C
  • Cytosar-U
  • NSC-63878

    • Drug: dexamethasone
    Given IV
    Other Names:
  • Decadron
  • NSC- 34521

    • Drug: etoposide
    Given IV
    Other Names:
  • VP-16
  • VePesid
  • NSC-14154p

    • Drug: idarubicin
    Given IV
    Other Names:
  • Idamycin
  • NSC-256439

    • Drug: ifosfamide
    Given IV
    Other Names:
  • Ifex
  • NSC-109724

    • Drug: leucovorin calcium

    Drug: mesna
    Given IV
    Other Names:
  • Mesnex
  • NSC-113891

    • Drug: pegaspargase
    Given IV
    Other Names:
  • PEG Asparaginase
  • PEG-ASP
  • K/H
  • KYOWA
  • HAKKO
  • NSC-644954

    • Drug: therapeutic hydrocortisone

    Drug: thioguanine

    Drug: vincristine sulfate
    Given IV
    Other Names:
  • Oncovin
  • NSC-675574

    • Radiation: low-LET electron therapy

    Radiation: low-LET photon therapy

    Drug: Methotrexate
    Given IV
    Other Names:
  • MTX
  • NSC-740

    		•
    Experimental: LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR

    Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, pegaspargase, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, PEG, Ifosfamide with Mesna) and Idarubicin), and Maintenance (4 x 12 courses) of ITT, Vincristine, Methotrexate, T-thioguanine.

    Drug: cytarabine
    Given IV
    Other Names:
  • Cytosine Arabinoside
  • Ara-C
  • Cytosar-U
  • NSC-63878

    • Drug: dexamethasone
    Given IV
    Other Names:
  • Decadron
  • NSC- 34521

    • Drug: etoposide
    Given IV
    Other Names:
  • VP-16
  • VePesid
  • NSC-14154p

    • Drug: idarubicin
    Given IV
    Other Names:
  • Idamycin
  • NSC-256439

    • Drug: ifosfamide
    Given IV
    Other Names:
  • Ifex
  • NSC-109724

    • Drug: leucovorin calcium

    Drug: mesna
    Given IV
    Other Names:
  • Mesnex
  • NSC-113891

    • Drug: pegaspargase
    Given IV
    Other Names:
  • PEG Asparaginase
  • PEG-ASP
  • K/H
  • KYOWA
  • HAKKO
  • NSC-644954

    • Drug: therapeutic hydrocortisone

    Drug: thioguanine

    Drug: vincristine sulfate
    Given IV
    Other Names:
  • Oncovin
  • NSC-675574

    • Radiation: low-LET cobalt-60 gamma ray therapy

    Radiation: low-LET electron therapy

    Radiation: low-LET photon therapy

    Drug: Methotrexate
    Given IV
    Other Names:
  • MTX
  • NSC-740

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Event Free Survival []

      The evaluation of the relationship between prognostic or treatment factors and EFS

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A to 20 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Long Beach Memorial Medical Center Long Beach California United States 90806
    2 Children's Hospital Los Angeles Los Angeles California United States 90027-0700
    3 Jonsson Comprehensive Cancer Center, UCLA Los Angeles California United States 90095-1781
    4 Children's Hospital of Orange County Orange California United States 92668
    5 UCSF Cancer Center and Cancer Research Institute San Francisco California United States 94115-0128
    6 Children's Hospital of Denver Denver Colorado United States 80218
    7 Children's National Medical Center Washington District of Columbia United States 20010-2970
    8 University of Chicago Cancer Research Center Chicago Illinois United States 60637
    9 Indiana University Cancer Center Indianapolis Indiana United States 46202-5265
    10 University of Iowa Hospitals and Clinics Iowa City Iowa United States 52242
    11 University of Michigan Comprehensive Cancer Center Ann Arbor Michigan United States 48109-0752
    12 University of Minnesota Cancer Center Minneapolis Minnesota United States 55455
    13 Mayo Clinic Cancer Center Rochester Minnesota United States 55905
    14 Children's Mercy Hospital - Kansas City Kansas City Missouri United States 64108
    15 University of Nebraska Medical Center Omaha Nebraska United States 68198-3330
    16 Kaplan Cancer Center New York New York United States 10016
    17 Memorial Sloan-Kettering Cancer Center New York New York United States 10021
    18 Herbert Irving Comprehensive Cancer Center New York New York United States 10032
    19 Lineberger Comprehensive Cancer Center, UNC Chapel Hill North Carolina United States 27599-7295
    20 Children's Hospital Medical Center - Cincinnati Cincinnati Ohio United States 45229-3039
    21 Ireland Cancer Center Cleveland Ohio United States 44106-5065
    22 Children's Hospital of Columbus Columbus Ohio United States 43205-2696
    23 Doernbecher Children's Hospital Portland Oregon United States 97201-3098
    24 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
    25 Children's Hospital of Pittsburgh Pittsburgh Pennsylvania United States 15213
    26 Vanderbilt Cancer Center Nashville Tennessee United States 37232-6838
    27 Huntsman Cancer Institute Salt Lake City Utah United States 84132
    28 Children's Hospital and Regional Medical Center - Seattle Seattle Washington United States 98105
    29 Fred Hutchinson Cancer Research Center Seattle Washington United States 98109
    30 University of Wisconsin Comprehensive Cancer Center Madison Wisconsin United States 53792
    31 Princess Margaret Hospital for Children Perth Western Australia Australia 6001
    32 British Columbia Children's Hospital Vancouver British Columbia Canada V6H 3V4
    33 IWK Grace Health Centre Halifax Nova Scotia Canada B3J 3G9

    Sponsors and Collaborators

    • Children's Oncology Group
    • National Cancer Institute (NCI)

    Investigators

    • Study Chair: Michael L.N. Willoughby, MD, Princess Margaret Hospital for Children

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Children's Oncology Group
    ClinicalTrials.gov Identifier:
    NCT00002816
    Other Study ID Numbers:
    • 1951
    • CCG-1951
    • CDR0000064968
    First Posted:
    Jun 23, 2004
    Last Update Posted:
    Aug 22, 2013
    Last Verified:
    Aug 1, 2013
    Keywords provided by Children's Oncology Group
    recurrent childhood acute lymphoblastic leukemia
    Additional relevant MeSH terms:
    Leukemia
    Precursor Cell Lymphoblastic Leukemia-Lymphoma
    Leukemia, Lymphoid
    Leucovorin
    Cobalt
    Cytarabine
    Dexamethasone
    Hydrocortisone
    Hydrocortisone 17-butyrate 21-propionate
    Hydrocortisone acetate
    Hydrocortisone hemisuccinate
    Methotrexate
    Etoposide
    Vincristine
    Ifosfamide
    Asparaginase
    Idarubicin
    Pegaspargase
    Thioguanine
    Levoleucovorin

    Study Results

    No Results Posted as of Aug 22, 2013