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Comparison of Different Combination Chemotherapy Regimens in Treating Children With Acute Lymphoblastic Leukemia

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00005945
First received: July 5, 2000
Last updated: May 7, 2013
Last verified: May 2013
History of Changes
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Giving more than one drug may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating childhood acute lymphoblastic leukemia.

PURPOSE: This randomized phase III trial is comparing different combination chemotherapy regimens to see how well they work in treating children with acute lymphoblastic leukemia.


Condition Intervention Phase
Leukemia
 Drug: cyclophosphamide
Drug: cytarabine
Drug: daunorubicin hydrochloride
Drug: dexamethasone
Drug: doxorubicin hydrochloride
Drug: mercaptopurine
Drug: methotrexate
Drug: pegaspargase
Drug: thioguanine
Drug: vincristine sulfate
Radiation: radiation therapy
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Escalating Dose Intravenous Methotrexate Without Leucovorin Rescue Versus Oral Methotrexate and Single Versus Double Delayed Intensification for Children With Standard Risk Acute Lymphoblastic Leukemia

Resource links provided by NLM:

U.S. FDA Resources

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

Primary Outcome Measures:
  • Event Free Survival [ Time Frame: Time of randomization ] [ Designated as safety issue: No ]
    The primary outcome index used in examining the randomized treatment groups will be event free survival (EFS) from the time of randomization (i.e., end of Consolidation), where the life table events will consist of the first occurrence of leukemic relapse at any site, death, or occurrence of a second malignancy.


Enrollment: 3054
Study Start Date: June 2000
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (regimen OS)
Day 28 of consolidation chemotherapy, Interim maintenance I chemotherapy of oral dexamethasone 2x daily on days 0-4 and 28-32; vincristine sulfate IV on days 0 and 28; oral methotrexate on days 0, 7, 14, 21, 28, 35, 42, and 49; oral mercaptopurine on days 0-49; and methotrexate IT on day 28. On day 56 of interim maintenance I chemotherapy, Delayed intensification chemotherapy of oral dexamethasone 2x on days 0-6 and 14-20; vincristine sulfate IV and doxorubicin hydrochloride (DOX) IV over 15 mins to 2 hours on days 0, 7, and 14; pegaspargase IM on day 3; cyclophosphamide (CTX) IV over 20-30 mins on day 28; oral thioguanine (TG) on days 28-41; cytarabine IV or subcutaneously (SC) daily on days 28-31 and 35-38; and methotrexate IT on days 0 and 28. CNS leukemia pts at diagnosis will receive cranial radiation therapy during the Consolidation phase. Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase.
 Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC-26271
Drug: cytarabine
Given IT
Other Names:
  • Cytosine Arabinoside
  • Ara_C
  • Cytosar-U
  • NSC-63878
Drug: dexamethasone
Given PO
Other Names:
  • Decadron
  • DM
  • NSC-34521
Drug: doxorubicin hydrochloride
Dose 25 g/m² IV Days 0, 7, 14, given over a period of 15 minutes to 2 hours
Other Names:
  • Adriamycin
  • NSC-123127
Drug: mercaptopurine
Given PO
Other Name: 6-MP
Drug: methotrexate
Given PO and IT
Other Name: MTX
Drug: pegaspargase
Given IM
Other Names:
  • PEG-asparaginase
  • Oncaspar
  • L-asparaginase with polyethylene glycol
Drug: thioguanine
Given PO
Other Names:
  • 6 TG
  • NSC-752
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • NSC-67574
  • VCR
Radiation: radiation therapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy
  • radiation
Experimental: Arm II (regimen OD)
Patients receive interim maintenance I chemotherapy, delayed intensification chemotherapy, and interim maintenance II chemotherapy as in arm I. Beginning on day 56 of interim maintenance II chemotherapy, patients then receive a second course of delayed intensification chemotherapy followed by maintenance chemotherapy as in arm I.
 Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC-26271
Drug: cytarabine
Given IT
Other Names:
  • Cytosine Arabinoside
  • Ara_C
  • Cytosar-U
  • NSC-63878
Drug: dexamethasone
Given PO
Other Names:
  • Decadron
  • DM
  • NSC-34521
Drug: doxorubicin hydrochloride
Dose 25 g/m² IV Days 0, 7, 14, given over a period of 15 minutes to 2 hours
Other Names:
  • Adriamycin
  • NSC-123127
Drug: mercaptopurine
Given PO
Other Name: 6-MP
Drug: methotrexate
Given PO and IT
Other Name: MTX
Drug: pegaspargase
Given IM
Other Names:
  • PEG-asparaginase
  • Oncaspar
  • L-asparaginase with polyethylene glycol
Drug: thioguanine
Given PO
Other Names:
  • 6 TG
  • NSC-752
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • NSC-67574
  • VCR
Radiation: radiation therapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy
  • radiation
Experimental: Arm III (regimen IS)
Beginning on day 28 of consolidation chemotherapy, patients receive interim maintenance I chemotherapy comprising vincristine sulfate IV; escalating doses of methotrexate IV on days 0, 10, 20, 30, and 40; and methotrexate IT on day 30. Patients then receive delayed intensification chemotherapy as in arm I. Patients receive interim maintenance II chemotherapy as in interim maintenance I chemotherapy, but with IV methotrexate starting at 2/3 of the maximum tolerated dose (MTD) attained in interim maintenance I chemotherapy. Patients then receive maintenance chemotherapy as in arm I.
 Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC-26271
Drug: cytarabine
Given IT
Other Names:
  • Cytosine Arabinoside
  • Ara_C
  • Cytosar-U
  • NSC-63878
Drug: dexamethasone
Given PO
Other Names:
  • Decadron
  • DM
  • NSC-34521
Drug: doxorubicin hydrochloride
Dose 25 g/m² IV Days 0, 7, 14, given over a period of 15 minutes to 2 hours
Other Names:
  • Adriamycin
  • NSC-123127
Drug: mercaptopurine
Given PO
Other Name: 6-MP
Drug: methotrexate
Given PO and IT
Other Name: MTX
Drug: pegaspargase
Given IM
Other Names:
  • PEG-asparaginase
  • Oncaspar
  • L-asparaginase with polyethylene glycol
Drug: thioguanine
Given PO
Other Names:
  • 6 TG
  • NSC-752
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • NSC-67574
  • VCR
Radiation: radiation therapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy
  • radiation
Experimental: Arm IV (regimen ID)
Patients receive interim maintenance I chemotherapy as in arm III, delayed intensification chemotherapy as in arm I, interim maintenance II chemotherapy as in arm III, delayed intensification II chemotherapy as in arm II, and maintenance chemotherapy as in arm I.
 Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC-26271
Drug: cytarabine
Given IT
Other Names:
  • Cytosine Arabinoside
  • Ara_C
  • Cytosar-U
  • NSC-63878
Drug: dexamethasone
Given PO
Other Names:
  • Decadron
  • DM
  • NSC-34521
Drug: doxorubicin hydrochloride
Dose 25 g/m² IV Days 0, 7, 14, given over a period of 15 minutes to 2 hours
Other Names:
  • Adriamycin
  • NSC-123127
Drug: mercaptopurine
Given PO
Other Name: 6-MP
Drug: methotrexate
Given PO and IT
Other Name: MTX
Drug: pegaspargase
Given IM
Other Names:
  • PEG-asparaginase
  • Oncaspar
  • L-asparaginase with polyethylene glycol
Drug: thioguanine
Given PO
Other Names:
  • 6 TG
  • NSC-752
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • NSC-67574
  • VCR
Radiation: radiation therapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy
  • radiation
Experimental: Augmented Treatment
Patients receive induction chemotherapy comprising daunorubicin hydrochloride IV continuously for 48 hours beginning no later than day 21; oral dexamethasone twice daily on days 14-27; and vincristine sulfate IV on days 14 and 21. Patients without CNS disease at diagnosis receive methotrexate IT on days 21 and 35. Patients with CNS disease at diagnosis receive methotrexate IT on days 21 and 28.
 Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC-26271
Drug: cytarabine
Given IT
Other Names:
  • Cytosine Arabinoside
  • Ara_C
  • Cytosar-U
  • NSC-63878
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidine
  • NSC-82151
Drug: dexamethasone
Given PO
Other Names:
  • Decadron
  • DM
  • NSC-34521
Drug: doxorubicin hydrochloride
Dose 25 g/m² IV Days 0, 7, 14, given over a period of 15 minutes to 2 hours
Other Names:
  • Adriamycin
  • NSC-123127
Drug: mercaptopurine
Given PO
Other Name: 6-MP
Drug: methotrexate
Given PO and IT
Other Name: MTX
Drug: pegaspargase
Given IM
Other Names:
  • PEG-asparaginase
  • Oncaspar
  • L-asparaginase with polyethylene glycol
Drug: thioguanine
Given PO
Other Names:
  • 6 TG
  • NSC-752
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • NSC-67574
  • VCR
Radiation: radiation therapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy
  • radiation

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   1 Year to 9 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of previously untreated B-cell precursor acute lymphoblastic leukemia

    • More than 25% L1 or L2 lymphoblasts
    • No more than 25% L3 lymphoblasts
    • WBC < 50,000/mm^3
  • No T-cell precursor acute lymphoblastic leukemia by immunophenotyping
  • Massive lymphadenopathy, massive splenomegaly, or large mediastinal mass allowed
  • CNS or testicular leukemia allowed
  • No patients found to have t(8;14)(q24;q32), t(8;22)(q24;q11), and t(2;8)(p11-p12;q24) (characteristic of Burkitt's lymphoma)

PATIENT CHARACTERISTICS:

Age:

  • 1 to 9

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • See Disease Characteristics

Hepatic:

  • Not specified

Renal:

  • Not specified

Other:

  • Not pregnant
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • No more than 72 hours since prior intrathecal cytarabine

Endocrine therapy:

  • At least 30 days since prior systemic corticosteroids given for more than 48 hours
  • Prior corticosteroids for mediastinal mass causing superior mediastinal syndrome allowed
  • Prior or concurrent inhaled corticosteroids allowed

Radiotherapy:

  • Prior radiotherapy for mediastinal mass causing superior mediastinal syndrome allowed
  • No concurrent spinal radiotherapy

Surgery:

  • Not specified
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00005945

  Show 130 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Study Chair: Yousif H. Matloub, MD University of Wisconsin, Madison
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Publications:
Matloub Y, Bostrom BC, Angiolillo AL, et al.: Children with NCI standard risk acute lymphoblastic leukemia (ALL) and TEL-AML1 or favorable chromosome trisomies are almost certain to be cured with graduated intensity therapy: results of the CCG - 1991 study. [Abstract] Blood 114 (22): A-320, 2009.
Matloub Y, Bostrom BC, Hunger SP, et al.: Escalating dose intravenous methotrexate without leucovorin rescue during interim maintenance is superior to oral methotrexate for children with standard risk acute lymphoblastic leukemia (SR-ALL): Children's Oncology Group study 1991. [Abstract] Blood 112 (11): A-9, 2008.
Matloub Y, Angiolillo A, Bostrom B, et al.: Double delayed intensification (DDI) is equivalent to single DI (SDI) in children with National Cancer Institute (NCI) standard-risk acute lymphoblastic leukemia (SR-ALL) treated on Children's Cancer Group (CCG) clinical trial 1991 (CCG-1991). [Abstract] Blood 108 (11): A-146, 2006.
Bruggers CS, Moyer-Mileur LJ, Ransdall L: Body composition, bone mineral acquisition, and cardiovascular fitness in children with standard risk acute lymphoblastic leukemia: response to a home-based exercise and nutrition education program. [Abstract] 2006 Pediatric Academic Societies' Annual Meeting, April 29 - May 2, San Francisco, CA. A-3505.46, 2006.
Matloub Y, Asselin BL, Stork LC, et al.: Outcome of children with T-Cell acute lymphoblastic leukemia (T-ALL) and standard risk (SR) features: results of CCG-1952, CCG-1991 and POG 9404. [Abstract] Blood 104 (11): A-680, 195a, 2004.

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00005945     History of Changes
Other Study ID Numbers: 1991, CCG-1991, CDR0000067855, NCI-2012-02333, U10CA98543
Study First Received: July 5, 2000
Last Updated: May 7, 2013
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
untreated childhood acute lymphoblastic leukemia
L1 childhood acute lymphoblastic leukemia
L2 childhood acute lymphoblastic leukemia
L3 childhood acute lymphoblastic leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
6-Mercaptopurine
Cytarabine
Methotrexate
Thioguanine
Cyclophosphamide
Pegaspargase
 Asparaginase
Daunorubicin
Dexamethasone
Doxorubicin
Vincristine
BB 1101
Dexamethasone acetate
Dexamethasone 21-phosphate
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents

ClinicalTrials.gov processed this record on May 16, 2013