NCT00057811

Brief Summary

Phase II trial to study the effectiveness of combining rituximab and rasburicase with combination chemotherapy in treating young patients who have newly diagnosed advanced B-cell leukemia or lymphoma. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug with rituximab may kill more cancer cells. Chemoprotective drugs such as rasburicase may protect kidney cells from the side effects of chemotherapy.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
97

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Jun 2004

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 7, 2003

Completed
2 days until next milestone

First Posted

Study publicly available on registry

April 9, 2003

Completed
1.1 years until next milestone

Study Start

First participant enrolled

June 1, 2004

Completed
5.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2009

Completed
4.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2014

Completed
2 months until next milestone

Results Posted

Study results publicly available

August 22, 2014

Completed
Last Updated

September 19, 2014

Status Verified

September 1, 2014

Enrollment Period

5.3 years

First QC Date

April 7, 2003

Results QC Date

January 21, 2014

Last Update Submit

September 10, 2014

Conditions

Outcome Measures

Primary Outcomes (4)

  • Grade ≥ 3 Stomatitis

    The incidence of grade ≥ 3 stomatitis. Grade 3 stomatitis: Confluent ulcerations or pseudomembranes; bleeding with minor trauma. Grade 4 stomatitis: Tissue necrosis; Significant spontaneous bleeding; life-threatening consequences

    Up to 1 year

  • Response Rate

    Response includes both complete and partial responses. Per protocol, complete Response is defined as the complete disappearance of all clinical evidence of disease by physical examination, by imaging studies, by bone marrow biopsy (where indicated), by CNS evaluation (where indicated) and by biopsy where there is a residual abnormality on an imaging study. Bone marrow must contain \<5% blasts. CSF WBC must be \<5/μL with no blasts or lymphomatous cells present. Partial response is defined as: at least a 50% reduction in the size of all measurable tumor areas. Each site is to be defined by the product of the maximum length, width and depth (3 dimensions). No lesion may progress. No new lesion may appear. Bone marrow must contain \<5% blasts. CSF WBC must be \<5/μL with no blasts or lymphomatous cells present..

    Up to 5 years

  • Minimal Residual Disease

    The presence or absence of tumor cells at the end of induction assessed by studying tissue and/or blood/marrow. Details of methods and criteria used can be found in Shiramizu at al. BJH 153:758-763, 2011 (full citation in the citation section).

    Not Provided

  • Toxic Death

    Implementation of the toxic death rate stopping rule, a death must be possibly, probably or definitely attributable to Rituximab and/or chemotherapy to be considered a toxic death.

    Up to 1 year

Study Arms (2)

Group B (chemotherapy, protective therapy, monoclonal antib.)

EXPERIMENTAL

Therapies given IV, IT, orally, or SC. Please see treatment outline. See Detailed Description.

Drug: doxorubicin hydrochlorideDrug: cyclophosphamideDrug: methotrexateDrug: rasburicaseDrug: leucovorin calciumDrug: prednisoneDrug: methylprednisoloneBiological: filgrastimBiological: rituximabDrug: cytarabineDrug: vincristine sulfateDrug: hydrocortisone sodium succinateOther: laboratory biomarker analysis

Group C (Chemotherapy, monoclonal antibody therapy)

EXPERIMENTAL

Therapies given IV, IT, orally, or subcutaneously (same as FAB B with the addition of etoposide and high-dose methotrexate). See Detailed Description.

Drug: doxorubicin hydrochlorideDrug: cyclophosphamideDrug: methotrexateDrug: leucovorin calciumDrug: prednisoneDrug: methylprednisoloneBiological: filgrastimBiological: rituximabDrug: cytarabineDrug: etoposideDrug: vincristine sulfateDrug: hydrocortisone sodium succinateOther: laboratory biomarker analysis

Interventions

Given IV, IT, or orally

Also known as: ADM, ADR, Adria, Adriamycin PFS, Adriamycin RDF
Group B (chemotherapy, protective therapy, monoclonal antib.)Group C (Chemotherapy, monoclonal antibody therapy)

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana
Group B (chemotherapy, protective therapy, monoclonal antib.)Group C (Chemotherapy, monoclonal antibody therapy)

Given IV or IT

Also known as: amethopterin, Folex, methylaminopterin, Mexate, MTX
Group B (chemotherapy, protective therapy, monoclonal antib.)Group C (Chemotherapy, monoclonal antibody therapy)

Given IV

Also known as: Elitek, NK-631, recombinant urate oxidase
Group B (chemotherapy, protective therapy, monoclonal antib.)

Given IV or orally

Also known as: CF, CFR, LV
Group B (chemotherapy, protective therapy, monoclonal antib.)Group C (Chemotherapy, monoclonal antibody therapy)

Given IV or orally

Also known as: DeCortin, Deltra
Group B (chemotherapy, protective therapy, monoclonal antib.)Group C (Chemotherapy, monoclonal antibody therapy)

Given IV or orally

Also known as: Depo-Medrol, Medrol, MePRDL, Solu-Medrol, Wyacort
Group B (chemotherapy, protective therapy, monoclonal antib.)Group C (Chemotherapy, monoclonal antibody therapy)
filgrastimBIOLOGICAL

Given subcutaneously

Also known as: G-CSF, Neupogen
Group B (chemotherapy, protective therapy, monoclonal antib.)Group C (Chemotherapy, monoclonal antibody therapy)
rituximabBIOLOGICAL

Given IV

Also known as: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan
Group B (chemotherapy, protective therapy, monoclonal antib.)Group C (Chemotherapy, monoclonal antibody therapy)

Given IT

Also known as: ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside
Group B (chemotherapy, protective therapy, monoclonal antib.)Group C (Chemotherapy, monoclonal antibody therapy)

Given IV

Also known as: EPEG, VP-16, VP-16-213
Group C (Chemotherapy, monoclonal antibody therapy)

Given IV

Also known as: leurocristine sulfate, VCR, Vincasar PFS
Group B (chemotherapy, protective therapy, monoclonal antib.)Group C (Chemotherapy, monoclonal antibody therapy)

Given IT

Also known as: Sodium hydrocortisone succinate, Solu-Cortef, Solu-Glyc
Group B (chemotherapy, protective therapy, monoclonal antib.)Group C (Chemotherapy, monoclonal antibody therapy)

Correlative studies

Group B (chemotherapy, protective therapy, monoclonal antib.)Group C (Chemotherapy, monoclonal antibody therapy)

Eligibility Criteria

Age1 Year - 29 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Newly diagnosed mature B-lineage (CD20-positive) leukemia or lymphoma by the REAL classification of 1 of the following subtypes:
  • Diffuse large cell lymphoma
  • Burkitt's lymphoma
  • High-grade B-cell lymphoma (Burkitt-like)
  • No B-cell anaplastic large cell Ki-1 positive lymphomas and B-lymphoblastic lymphomas
  • One of the following FAB prognostic groups:
  • Group B (intermediate risk)
  • Group C (high risk)
  • Bone marrow involvement with at least 25% blasts and/or CNS involvement meeting 1 or more of the following criteria:
  • Any L3 blasts in cerebrospinal fluid
  • Cranial nerve palsy (if not explained by extracranial tumor)
  • Clinical spinal cord compression
  • Isolated intracerebral mass
  • Parameningeal extension (cranial and/or spinal)
  • Hepatitis B status known
  • +11 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Children's Oncology Group

Arcadia, California, 91006-3776, United States

Location

Related Publications (2)

  • Shiramizu B, Goldman S, Kusao I, Agsalda M, Lynch J, Smith L, Harrison L, Morris E, Gross TG, Sanger W, Perkins S, Cairo MS. Minimal disease assessment in the treatment of children and adolescents with intermediate-risk (Stage III/IV) B-cell non-Hodgkin lymphoma: a children's oncology group report. Br J Haematol. 2011 Jun;153(6):758-63. doi: 10.1111/j.1365-2141.2011.08681.x. Epub 2011 Apr 18.

    PMID: 21496005BACKGROUND
  • Frazer JK, Li KJ, Galardy PJ, Perkins SL, Auperin A, Anderson JR, Pinkerton R, Buxton A, Gross TG, Michon J, Leverger G, Weinstein HJ, Harrison L, Shiramizu B, Barth MJ, Goldman SC, Patte C, Cairo MS. Excellent outcomes in children and adolescents with CNS+ Burkitt lymphoma or other mature B-NHL using only intrathecal and systemic chemoimmunotherapy: results from FAB/LMB96 and COG ANHL01P1. Br J Haematol. 2019 Apr;185(2):374-377. doi: 10.1111/bjh.15520. Epub 2018 Aug 16. No abstract available.

MeSH Terms

Conditions

Burkitt LymphomaLymphoma, Large B-Cell, DiffuseDendritic Cell Sarcoma, Interdigitating

Interventions

DoxorubicinCyclophosphamideMethotrexatemerphosrasburicasePeplomycinUrate OxidaseLeucovorinPrednisoneMethylprednisoloneMethylprednisolone AcetateMethylprednisolone HemisuccinateFilgrastimGranulocyte Colony-Stimulating FactorRituximabCytarabineEtoposideVincristineHydrocortisonehydrocortisone hemisuccinate

Condition Hierarchy (Ancestors)

Epstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLymphoma, B-CellLymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesHistiocytic Disorders, MalignantHistiocytosis

Intervention Hierarchy (Ancestors)

DaunorubicinAnthracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic CompoundsAminoglycosidesGlycosidesCarbohydratesPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedPhosphoramidesOrganophosphorus CompoundsAminopterinPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsBleomycinGlycopeptidesGlycoconjugatesPeptidesAmino Acids, Peptides, and ProteinsOxidoreductasesEnzymesEnzymes and CoenzymesFormyltetrahydrofolatesTetrahydrofolatesFolic AcidCoenzymesPregnadienediolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPrednisolonePregnadienetriolsColony-Stimulating FactorsGlycoproteinsHematopoietic Cell Growth FactorsCytokinesIntercellular Signaling Peptides and ProteinsProteinsBiological FactorsAntibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsSerum GlobulinsGlobulinsCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingArabinonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesPodophyllotoxinTetrahydronaphthalenesNaphthalenesGlucosidesVinca AlkaloidsSecologanin Tryptamine AlkaloidsIndole AlkaloidsAlkaloidsIndolesIndolizidinesIndolizinesPregnenedionesPregnenes11-HydroxycorticosteroidsHydroxycorticosteroidsAdrenal Cortex HormonesHormonesHormones, Hormone Substitutes, and Hormone Antagonists17-Hydroxycorticosteroids

Results Point of Contact

Title
Results Reporting Coordinator
Organization
Children's Oncology Group

Study Officials

  • Mitchell Cairo, MD CCRP

    Children's Oncology Group

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NETWORK
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 7, 2003

First Posted

April 9, 2003

Study Start

June 1, 2004

Primary Completion

October 1, 2009

Study Completion

July 1, 2014

Last Updated

September 19, 2014

Results First Posted

August 22, 2014

Record last verified: 2014-09

Locations