Trial record 1 of 1 for:    AALL0433
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Low-Dose or High-Dose Vincristine and Combination Chemotherapy in Treating Young Patients With Relapsed B-Cell 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:
NCT00381680
First received: September 26, 2006
Last updated: February 28, 2014
Last verified: February 2014
  Purpose

This randomized phase III trial is studying low-dose vincristine to see how well it works compared with high-dose vincristine (closed to accrual as of 09/2010) when given together with different combination chemotherapy regimens in treating young patients with intermediate-risk relapsed B-cell 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) and giving the drugs in different ways and different doses may kill more cancer cells. It is not yet known whether low-dose vincristine is more effective than high-dose vincristine (closed to accrual as of 09/2010) when given together with different combination chemotherapy regimens in treating acute lymphoblastic leukemia.


Condition Intervention Phase
B-cell Childhood Acute Lymphoblastic Leukemia
L1 Childhood Acute Lymphoblastic Leukemia
L2 Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Acute Lymphoblastic Leukemia
Drug: vincristine sulfate
Drug: prednisone
Drug: doxorubicin hydrochloride
Drug: pegaspargase
Drug: cytarabine
Drug: methotrexate
Drug: dexamethasone
Drug: etoposide
Drug: cyclophosphamide
Drug: leucovorin calcium
Biological: filgrastim
Drug: asparaginase
Drug: mercaptopurine
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: INTENSIVE TREATMENT FOR INTERMEDIATE-RISK RELAPSE OF CHILDHOOD B-PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA (ALL): A RANDOMIZED TRIAL OF VINCRISTINE STRATEGIES

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Efficacy of therapy of an intensive chemotherapy regimen (based on POG 9412) for patients with intermediate-risk relapse of childhood B-precursor ALL [ Time Frame: Assessed up to 5 years ] [ Designated as safety issue: No ]
    Power calculations are based on the assumption of proportional hazards, and using the log rank test (alpha=0.1, one-sided test). The efficacy stopping boundaries to be used will be based on the alpha x (time)^2 spending function. The study will also be monitored for futility. The lower boundaries are based on testing the alternative hypothesis at the 0.005 level.

  • Event-free survival [ Time Frame: At 3 years ] [ Designated as safety issue: No ]
    A 95% confidence interval will be constructed using data on the standard dosing VCR arm at the time of study completion. If the lower bound of the confidence interval is larger than 40%, then the intensified chemotherapy will be deemed as efficacious. correlation between MRD and EFS will be essentially descriptive.


Secondary Outcome Measures:
  • Frequency and severity of adverse effects assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 107 weeks ] [ Designated as safety issue: Yes ]
    If 7 or more of the first 30 patients (combined in both arms) experience Grade 3 peripheral neurotoxicity then the accrual of adolescents will be temporarily closed. A one-sided Z-test for testing the equality of proportions with alpha=0.05 and with early stopping boundaries based on the t1/2 alpha spending function will be used. Osteonecrosis will be closely monitored on this study - overall and among patients less than ten years and those greater than or equal to ten years of age at the time of enrollment on study.

  • Gene expression profile of early versus late marrow relapse by DNA microarray [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]
    Genes predictive of outcome will be identified using statistical methods and multiple supervised machine learning algorithms with rigorous cross validation. Profiles will be correlated with time of relapse (early vs. late). Expression profiles derived from relapse samples will be compared to the gene expression classifiers derived from pretreatment samples. Three-year EFS for these two groups varies from less than 20% for early marrow relapse to 40% - 50% for late relapse.


Enrollment: 275
Study Start Date: March 2007
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (low-dose vincristine and combination chemotherapy)
Pts receive cranial radiation therapy. Induction of low-dose vincristine sulfate in combo chemotherapy (etoposide phosphate, prednisone, doxorubicin hydrochloride, pegaspargase, cytarabine, methotrexate) on wks 1-5. CNS+ pts receive (ITT-methotrexate, therapeutic hydrocortisone, cytarabine). They also receive additional induction (etoposide phosphate, cyclophosphamide, methotrexate, leucovorin calcium, cytarabine, asparaginase and filgrastim) on wks 6-10 & 11-15, an intensified regimen (vincristine, methotrexate, leucovorin calcium, mercaptopurine, etoposide phosphate, cyclophosphamide) on wks 16-7, re-induction regimen on wks 28-32 (vincristine,doxorubicin,dexamethasone,pegaspargase, methotrexate), intensified regimen on wks 33-56 (cytarabine, pegaspargase, vincristine sulfate, methotrexate, leucovorin calcium,mercaptopurine,etoposide and cyclophosphamide), a maintenance regimen on wks 57-106 (methotrexate, mercaptopurine, dexamethasone, vincristine, cyclophosphamide).
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: prednisone
Given PO
Other Names:
  • DeCortin
  • Deltra
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: pegaspargase
Given IM
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: cytarabine
Given IT or IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: methotrexate
Given IT or IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: dexamethasone
Given PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: leucovorin calcium
Given IV or PO
Other Names:
  • CF
  • CFR
  • LV
Biological: filgrastim
Given IV or SC
Other Names:
  • G-CSF
  • Neupogen
Drug: asparaginase
Given IM
Other Names:
  • ASNase
  • Colaspase
  • Crasnitin
  • Elspar
  • L-ASP
Drug: mercaptopurine
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Experimental: Arm II (high-dose vincristine and combination chemotherapy)
Patients receive induction therapy comprising high-dose vincristine sulfate in combination with chemotherapy on weeks 1-5. They also receive additional induction therapy on weeks 6-10 and 11-15, an intensified chemotherapy regimen on weeks 16-7, a re-induction regimen on weeks 28-32, an intensified regimen on weeks 33-56, and a maintenance regimen on weeks 57-106.(closed to accrual as of 09/2010).
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: prednisone
Given PO
Other Names:
  • DeCortin
  • Deltra
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: pegaspargase
Given IM
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: cytarabine
Given IT or IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: methotrexate
Given IT or IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: dexamethasone
Given PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: leucovorin calcium
Given IV or PO
Other Names:
  • CF
  • CFR
  • LV
Biological: filgrastim
Given IV or SC
Other Names:
  • G-CSF
  • Neupogen
Drug: asparaginase
Given IM
Other Names:
  • ASNase
  • Colaspase
  • Crasnitin
  • Elspar
  • L-ASP
Drug: mercaptopurine
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   1 Year to 29 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of acute lymphoblastic leukemia (ALL)

    • Bone marrow with > 25% L1 or L2 lymphoblasts (M3 marrow)

      • Patients with > 25% L3 marrow lymphoblasts and/or evidence of c-myc translocation are not eligible (considered Burkitt's or mature B-cell leukemia)
  • Intermediate-risk relapsed disease, meeting 1 of the following criteria:

    • Bone marrow relapse ≥ 36 months after initial diagnosis (defined as M3 marrow after previous remission from ALL)
    • Combined bone marrow and extramedullary (CNS* and/or testicular**) relapse ≥ 36 months after initial diagnosis
    • Isolated extramedullary (CNS* and/or testicular**) relapse < 18 months after initial diagnosis
  • The following subtypes are not allowed:

    • T-lineage ALL
    • Mature B-cell (Burkitt's) leukemia (defined as L3 morphology and/or evidence of c-myc translocation)
    • Philadelphia-chromosome positive disease
  • No Down syndrome (trisomy 21)
  • Shortening fraction >= 27% by echocardiogram OR ejection fraction >= 50% by radionuclide angiogram
  • Bilirubin < 3.0 mg/dL
  • Not pregnant
  • Fertile patients must use effective contraception
  • No history of peripheral neuropathy >= grade 3 within the past month
  • No toxicity (i.e. peripheral neuropathy) >= grade 3 attributable to vincristine within the past month
  • At least 5 days since prior intrathecal chemotherapy
  • No prior hematopoietic stem cell or marrow transplantation
  • No prior cranial radiotherapy > 1200 cGy (for patients with CNS relapse)
  • No concurrent stem cell transplant
  • No concurrent alternative therapy
  • No concurrent itraconazole in patients receiving vincristine
  • No concurrent intensity-modulated radiotherapy
  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: NCT00381680

  Show 173 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Glen Lew, MD Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00381680     History of Changes
Other Study ID Numbers: AALL0433, NCI-2009-00306, COG-AALL0433, CDR0000495359, U10CA098543
Study First Received: September 26, 2006
Last Updated: February 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Burkitt Lymphoma
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoma, B-Cell
Neoplasms, Experimental
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
6-Mercaptopurine
Cytarabine
Methotrexate
Cyclophosphamide
Etoposide phosphate
Pegaspargase
Asparaginase
Dexamethasone
Doxorubicin
Etoposide
Prednisone

ClinicalTrials.gov processed this record on July 29, 2014