Trial record 1 of 1 for:    01190930
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Risk-Adapted Chemotherapy in Younger Patients With Newly Diagnosed Standard-Risk Acute Lymphoblastic Leukemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Children's Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT01190930
First received: August 27, 2010
Last updated: February 17, 2014
Last verified: February 2014
  Purpose

This partially randomized phase III clinical trial is studying different combinations of risk-adapted chemotherapy regimens and their side effects and comparing how well they work in treating younger patients with newly diagnosed standard-risk acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy), giving the drugs in different doses, and giving the drugs in different combinations may kill more cancer cells.


Condition Intervention Phase
B-cell Childhood Acute Lymphoblastic Leukemia
Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia
Untreated Adult Acute Lymphoblastic Leukemia
Untreated Childhood Acute Lymphoblastic Leukemia
Drug: doxorubicin hydrochloride
Drug: cytarabine
Drug: vincristine sulfate
Drug: dexamethasone
Drug: pegaspargase
Drug: methotrexate
Drug: mercaptopurine tablet
Drug: leucovorin calcium
Drug: cyclophosphamide
Drug: thioguanine
Procedure: quality-of-life assessment
Other: questionnaire administration
Other: laboratory biomarker analysis
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of Patients With Newly Diagnosed Standard Risk B-Precursor Acute Lymphoblastic Leukemia (ALL)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Improvement in DFS from 93% to 96% in AR patients based on the methotrexate randomization [ Time Frame: Time from randomization at the end of interim maintenance II to first event (relapse, second malignancy, remission death) or date of last contact, assessed up to 5 years ] [ Designated as safety issue: No ]
    All power calculations are based on the assumption of proportional hazards, and using the log rank test (alpha = 5%) with 5 planned analyses of the data for interim monitoring purposes (MTX question for AR patients). The study will also be monitored for futility.

  • Determination of whether the 5-year DFS in AR patients is adversely affected by the reduced pulses in maintenance [ Time Frame: Every 4 weeks versus every 8 weeks from the start of reduced pulse maintenance, assessed up to 5 years ] [ Designated as safety issue: No ]
    If it is found that there is a decrease in DFS due to the reduced pulses, comparison of outcomes between the two MTX regimens will be restricted to the every 4 week pulses arms. A Cox proportional hazards model will be used to test for quantitative interaction in this 2x2 factorial design.

  • Determination of whether less intensive therapy will maintain DFS >= 95% for LR patients randomized to 1 of 2 low-intensity regimens [ Time Frame: Time from end of Induction to first event (relapse, second malignancy, remission death) or date of last contact, assessed up to 5 years ] [ Designated as safety issue: No ]
    The 5-year DFS for these patients will be estimated on the 2 low intensity regimens. Interim analysis will also be conducted, for each of the 2 low intensity regimens to protect against lower DFS for the LR patients, based on the estimated hazard rate.

  • DFS for Down syndrome patients [ Time Frame: Time from end of Induction to first event (relapse, second malignancy, remission death) or date of last contact, assessed up to 5 years ] [ Designated as safety issue: No ]
    The 5-year DFS for these patients will be estimated on modified therapy.


Secondary Outcome Measures:
  • Burden of therapy in AR patients overall at different time points during and at the end of therapy [ Time Frame: Up to 30 months after beginning of maintenance (off-therapy time point for boys) ] [ Designated as safety issue: No ]
    Assessed by the Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), the Child Vulnerability Scale, and by the Behavior Assessment Scales of Children-Second Edition, Parent Rating Scale (BASC-2 PRS). Standardized scores for the sub-scales of the PedsQL 4.0 will be calculated using age and gender specific normative data.

  • Burden of therapy in AR patients randomized to every 4-week vs every 12-week pulses during maintenance therapy [ Time Frame: Up to 30 months after beginning of Maintenance (off-therapy time point for boys) ] [ Designated as safety issue: No ]
    Assessed by the Pediatric Quality of Life Instrument scores, the Child Vulnerability Scale, and emotional symptoms (measured by the BASC-2 PRS), adjusting for age, gender, and family income. Comparison of differences in means (of the continuous measures) between the 2 randomization groups with 2-sample t-tests will be done. If the continuous data are not normally distributed, a non-parametric statistical measure will be used.


Estimated Enrollment: 5872
Study Start Date: August 2010
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on days 1, 29, and 57; oral dexamethasone BID on days 1-5, 29-33, and 57-61; oral methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; oral mercaptopurine on days 1-84; and IT methotrexate on day 1.
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: dexamethasone
Given orally (PO) or IV
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: methotrexate
Given IT, PO, or IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: mercaptopurine tablet
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: questionnaire administration
Ancillary studies
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm B (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on days 1, 29, and 57; oral dexamethasone BID on days 1-5, 29-33, and 57-61; higher-dose oral methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; oral mercaptopurine on days 1-84; and IT methotrexate on day 1.
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: dexamethasone
Given orally (PO) or IV
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: methotrexate
Given IT, PO, or IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: mercaptopurine tablet
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: questionnaire administration
Ancillary studies
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm C (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on day 1; oral dexamethasone BID on days 1-5; oral methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; oral mercaptopurine on days 1-84; and IT methotrexate on day 1.
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: dexamethasone
Given orally (PO) or IV
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: methotrexate
Given IT, PO, or IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: mercaptopurine tablet
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: questionnaire administration
Ancillary studies
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm D (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on day 1; oral dexamethasone BID on days 1-5; higher-dose oral methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; oral mercaptopurine on days 1-84; and IT methotrexate on day 1.
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: dexamethasone
Given orally (PO) or IV
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: methotrexate
Given IT, PO, or IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: mercaptopurine tablet
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: questionnaire administration
Ancillary studies
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm LR-M (risk-adapted chemotherapy)
Patients receive consolidation and maintenance therapy.
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: dexamethasone
Given orally (PO) or IV
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: methotrexate
Given IT, PO, or IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: mercaptopurine tablet
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Drug: leucovorin calcium
Given PO
Other Names:
  • CF
  • CFR
  • LV
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: questionnaire administration
Ancillary studies
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm LR-C (risk-adapted chemotherapy)
Patients receive consolidation, interim maintenance I, delayed intensification, interim maintenance II, and maintenance therapy.
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: cytarabine
Given IT, IV, or SC
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: dexamethasone
Given orally (PO) or IV
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: pegaspargase
Given IV
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: methotrexate
Given IT, PO, or IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: mercaptopurine tablet
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: thioguanine
Given PO
Other Name: 6-TG
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: questionnaire administration
Ancillary studies
Other: laboratory biomarker analysis
Correlative studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   1 Year to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • B-ALL patients must be enrolled on AALL08B1 prior to treatment and enrollment on AALL0932
  • Patients must have newly diagnosed NCI Standard Risk B-ALL or B-LLy Murphy Stages I or II; patients with Down syndrome are also eligible

    • Note: For B-LLy patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to B-ALL; for tissue processed by other means (i.e. paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of B-LLy defined by the submitting institution will be accepted
  • Meets the criteria for one of the following risk groups after induction therapy

    • Low-risk (LR) disease, defined as meeting the following criteria:

      • Favorable genetics: the presence of simultaneous trisomies of chromosome 4 and 10 (double trisomy; DT) or ETV6/RUNX1 fusion
      • Day 8 peripheral blood (PB) minimal residual disease (MRD) < 0.01%
      • Day 29 bone marrow (BM) MRD < 0.01%
      • No CNS2*, CNS3*, or testicular† leukemia
      • No steroid pretreatment
      • No Down syndrome (DS)
    • Average-risk disease, defined as meeting one of the following sets of criteria:

      • Favorable genetics: the presence of DT or ETV6/RUNX1 fusions
      • Day 8 PB MRD ≥ 0.01% or CNS2* status
      • Day 29 BM MRD < 0.01%
      • No CNS3* or testicular† leukemia
      • No DS
      • Neither favorable nor unfavorable cytogenetics‡
      • Day 8 PB MRD < 1%
      • Day 29 BM MRD < 0.01%
      • No CNS3* or testicular† leukemia
      • No DS
    • Standard-risk with Down syndrome (DS), defined as meeting the following criteria:

      • No mixed-lineage leukemia (MLL)-rearrangement, hypodiploidy**, or Philadelphia chromosome-positive (Ph+) disease††
      • Day 29 BM MRD < 0.01%‡‡
      • No CNS3* or testicular† leukemia
  • WBC count < 50,000/mm^3
  • No prior cytotoxic chemotherapy for the current diagnosis of ALL or any cancer diagnosed previously

    • Steroids* and intrathecal cytarabine for the current diagnosis of ALL allowed

      • Inhalational steroids are not considered as pretreatment
  • Patients with testicular leukemia are not eligible for AALL0932
  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: NCT01190930

Contacts
Contact: Peter Adamson, MD 612-624-8651 Adamson@email.chop.edu

  Show 218 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Anne Angiolillo, MD Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT01190930     History of Changes
Other Study ID Numbers: AALL0932, NCI-2011-02599, CDR0000683227, AALL0932, AALL0932, U10CA098543
Study First Received: August 27, 2010
Last Updated: February 17, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Philadelphia Chromosome
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Translocation, Genetic
Chromosome Aberrations
Pathologic Processes
6-Mercaptopurine
Cytarabine
Methotrexate
Thioguanine
Cyclophosphamide
Pegaspargase
Asparaginase
Dexamethasone
Doxorubicin
Vincristine
BB 1101
Dexamethasone acetate
Dexamethasone 21-phosphate
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 22, 2014