Combination Chemotherapy in Treating Children With Relapsed Acute Lymphoblastic Leukemia

NCT ID: NCT00002816

Last Updated: 2013-08-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

1996-12-31

Study Completion Date

2006-04-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Leukemia

Keywords

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recurrent childhood acute lymphoblastic leukemia

Study Design

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Primary Study Purpose

TREATMENT

Study Groups

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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.

Group Type EXPERIMENTAL

cytarabine

Intervention Type DRUG

Given IV

dexamethasone

Intervention Type DRUG

Given IV

etoposide

Intervention Type DRUG

Given IV

idarubicin

Intervention Type DRUG

Given IV

ifosfamide

Intervention Type DRUG

Given IV

leucovorin calcium

Intervention Type DRUG

mesna

Intervention Type DRUG

Given IV

pegaspargase

Intervention Type DRUG

Given IV

therapeutic hydrocortisone

Intervention Type DRUG

thioguanine

Intervention Type DRUG

vincristine sulfate

Intervention Type DRUG

Given IV

low-LET electron therapy

Intervention Type RADIATION

low-LET photon therapy

Intervention Type RADIATION

Methotrexate

Intervention Type DRUG

Given IV

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.

Group Type EXPERIMENTAL

cytarabine

Intervention Type DRUG

Given IV

dexamethasone

Intervention Type DRUG

Given IV

etoposide

Intervention Type DRUG

Given IV

idarubicin

Intervention Type DRUG

Given IV

ifosfamide

Intervention Type DRUG

Given IV

leucovorin calcium

Intervention Type DRUG

mesna

Intervention Type DRUG

Given IV

pegaspargase

Intervention Type DRUG

Given IV

therapeutic hydrocortisone

Intervention Type DRUG

thioguanine

Intervention Type DRUG

vincristine sulfate

Intervention Type DRUG

Given IV

low-LET cobalt-60 gamma ray therapy

Intervention Type RADIATION

low-LET electron therapy

Intervention Type RADIATION

low-LET photon therapy

Intervention Type RADIATION

Methotrexate

Intervention Type DRUG

Given IV

Interventions

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cytarabine

Given IV

Intervention Type DRUG

dexamethasone

Given IV

Intervention Type DRUG

etoposide

Given IV

Intervention Type DRUG

idarubicin

Given IV

Intervention Type DRUG

ifosfamide

Given IV

Intervention Type DRUG

leucovorin calcium

Intervention Type DRUG

mesna

Given IV

Intervention Type DRUG

pegaspargase

Given IV

Intervention Type DRUG

therapeutic hydrocortisone

Intervention Type DRUG

thioguanine

Intervention Type DRUG

vincristine sulfate

Given IV

Intervention Type DRUG

low-LET cobalt-60 gamma ray therapy

Intervention Type RADIATION

low-LET electron therapy

Intervention Type RADIATION

low-LET photon therapy

Intervention Type RADIATION

Methotrexate

Given IV

Intervention Type DRUG

Other Intervention Names

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Cytosine Arabinoside Ara-C Cytosar-U NSC-63878 Decadron NSC- 34521 VP-16 VePesid NSC-14154p Idamycin NSC-256439 Ifex NSC-109724 Mesnex NSC-113891 PEG Asparaginase PEG-ASP K/H KYOWA HAKKO NSC-644954 Oncovin NSC-675574 MTX NSC-740

Eligibility Criteria

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Inclusion Criteria

PATIENT CHARACTERISTICS: See General Eligibility Criteria
Maximum Eligible Age

20 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael L.N. Willoughby, MD

Role: STUDY_CHAIR

Princess Margaret Hospital for Children

Locations

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Long Beach Memorial Medical Center

Long Beach, California, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, United States

Site Status

Children's Hospital of Denver

Denver, Colorado, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Site Status

Indiana University Cancer Center

Indianapolis, Indiana, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

University of Minnesota Cancer Center

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

Children's Mercy Hospital - Kansas City

Kansas City, Missouri, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Kaplan Cancer Center

New York, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Site Status

Lineberger Comprehensive Cancer Center, UNC

Chapel Hill, North Carolina, United States

Site Status

Children's Hospital Medical Center - Cincinnati

Cincinnati, Ohio, United States

Site Status

Ireland Cancer Center

Cleveland, Ohio, United States

Site Status

Children's Hospital of Columbus

Columbus, Ohio, United States

Site Status

Doernbecher Children's Hospital

Portland, Oregon, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Vanderbilt Cancer Center

Nashville, Tennessee, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, United States

Site Status

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, United States

Site Status

Princess Margaret Hospital for Children

Perth, Western Australia, Australia

Site Status

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

Site Status

IWK Grace Health Centre

Halifax, Nova Scotia, Canada

Site Status

Countries

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United States Australia Canada

References

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Uckun FM, Gaynon PS, Stram DO, Sensel MG, Sarquis MB, Willoughby M. Bone marrow leukemic progenitor cell content in pediatric T-lineage acute lymphoblastic leukemia patients with an isolated extramedullary first relapse. Leuk Lymphoma. 2001 Jan;40(3-4):279-85. doi: 10.3109/10428190109057926.

Reference Type RESULT
PMID: 11426549 (View on PubMed)

Uckun FM, Gaynon PS, Stram DO, Sensel MG, Sarquis MB, Lazarus KH, Willoughby M. Paucity of leukemic progenitor cells in the bone marrow of pediatric B-lineage acute lymphoblastic leukemia patients with an isolated extramedullary first relapse. Clin Cancer Res. 1999 Sep;5(9):2415-20.

Reference Type RESULT
PMID: 10499612 (View on PubMed)

Other Identifiers

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CCG-1951

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000064968

Identifier Type: OTHER

Identifier Source: secondary_id

1951

Identifier Type: -

Identifier Source: org_study_id