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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00005945
First received: July 5, 2000
Last updated: September 8, 2014
Last verified: September 2014
  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:


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: November 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Induction Not Randomized
Standard Induction (28 Days). M3 Marrow at Day 28 and Off Protocol Therapy.
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC-26271
Drug: dexamethasone
Given PO
Other Names:
  • Decadron
  • DM
  • NSC-34521
Drug: methotrexate
Given PO and IT
Other Name: MTX
Drug: pegaspargase
Given IM
Other Names:
  • PEG-asparaginase
  • Oncaspar
  • L-asparaginase with polyethylene glycol
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • NSC-67574
  • VCR
Experimental: Induction and Oral MTX, Double Delayed Intensification CNS
Patients with CNS disease at diagnosis, without other unfavorable characteristics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Cranial 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: Induction and Augmented regimen (IV MTX, Double DI)
Patients with unfavorable characteristics. Standard Induction (14 Days), Augmented Induction (Days 14-35), Consolidation (9 weeks), Interim Maintenance I (56 Days), Delayed Intensification I (2 months), Interim Maintenance II (2 months), Delayed Intensification II (2 months), then Maintenance (84 day courses).
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
Experimental: Induction and Oral MTX, Single Delayed Intensification
Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months) then Maintenance (12 week cycles). 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: Induction and Oral MTX, Double Delayed Intensification
Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). 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: Induction and IV MTX, Single Delayed Intensification
Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months) then Maintenance (12 week cycles). 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: Induction and IV MTX, Double Delayed Intensification
Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in event free remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). 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

  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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005945

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

Additional Information:
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: September 8, 2014
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
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Asparaginase
Cyclophosphamide
Daunorubicin
Dexamethasone
Doxorubicin
Liposomal doxorubicin
Methotrexate
Pegaspargase
Vincristine
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Alkylating Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antiemetics
Antimetabolites
Antimetabolites, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal

ClinicalTrials.gov processed this record on October 23, 2014