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Combination Chemotherapy in Treating Children With Relapsed Acute Lymphoblastic Leukemia

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00002816
First Posted: June 23, 2004
Last Update Posted: August 22, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
  Purpose

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 Intervention Phase
Leukemia Drug: cytarabine Drug: dexamethasone Drug: etoposide Drug: idarubicin Drug: ifosfamide Drug: leucovorin calcium Drug: mesna Drug: pegaspargase Drug: therapeutic hydrocortisone Drug: thioguanine Drug: vincristine sulfate Radiation: low-LET cobalt-60 gamma ray therapy Radiation: low-LET electron therapy Radiation: low-LET photon therapy Drug: Methotrexate Phase 3

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: EXTRAMEDULLARY RELAPSE AND OCCULT BONE MARROW INVOLVEMENT IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA: A PHASE III GROUP-WIDE STUDY

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Event Free Survival
    The evaluation of the relationship between prognostic or treatment factors and EFS


Estimated Enrollment: 120
Study Start Date: December 1996
Study Completion Date: April 2006
Primary Completion Date: November 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   up to 20 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00002816


  Show 33 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Study Chair: Michael L.N. Willoughby, MD Princess Margaret Hospital for Children
  More Information

Publications:
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00002816     History of Changes
Other Study ID Numbers: 1951
CCG-1951 ( Other Identifier: Children's Cancer Group )
CDR0000064968 ( Other Identifier: Clinical Trials.gov )
First Submitted: November 1, 1999
First Posted: June 23, 2004
Last Update Posted: August 22, 2013
Last Verified: August 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
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Cortisol succinate
Dexamethasone
Hydrocortisone
Etoposide phosphate
Isophosphamide mustard
Pegaspargase
Methotrexate
Etoposide
Cytarabine
Vincristine
Ifosfamide
Idarubicin
Asparaginase
Thioguanine
BB 1101
Calcium, Dietary
Levoleucovorin
Leucovorin