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Rituximab and Combination Chemotherapy in Treating Patients With Stage II, Stage III, or Stage IV Diffuse Large B-Cell Non-Hodgkin's Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00274924
Recruitment Status : Completed
First Posted : January 11, 2006
Results First Posted : February 24, 2014
Last Update Posted : November 17, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group

Tracking Information
First Submitted Date  ICMJE January 10, 2006
First Posted Date  ICMJE January 11, 2006
Results First Submitted Date  ICMJE January 9, 2014
Results First Posted Date  ICMJE February 24, 2014
Last Update Posted Date November 17, 2020
Actual Study Start Date  ICMJE April 2006
Actual Primary Completion Date June 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 10, 2014)
2-year Progression-Free Survival (PFS) [ Time Frame: Assessed every 4 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, then every 12 months if patient is 5-10 years from study entry. ]
2-year progression-free survival is defined as the probability of patients who remain alive and progression free at 2 years from study entry. The method of Kaplan and Meier (1958) was used to estimate PFS.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 10, 2014)
5-year Overall Survival [ Time Frame: Every 4 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, then every 12 months if patient is 5-10 years from study entry. ]
5-year overall survival is defined as the probability of patients who remain alive at 5 years from study entry. The method of Kaplan and Meier (1958) was used to estimate overall survival.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Rituximab and Combination Chemotherapy in Treating Patients With Stage II, Stage III, or Stage IV Diffuse Large B-Cell Non-Hodgkin's Lymphoma
Official Title  ICMJE Response-Adapted Therapy for Aggressive Non-Hodgkin's Lymphomas Based on Early [18F] FDG-PET Scanning
Brief Summary

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. 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 rituximab together with combination chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy works in treating patients with stage II, stage III, or stage IV diffuse large B-cell non-Hodgkin's lymphoma.

Detailed Description

OBJECTIVES:

Primary

  • Determine the 2-year progression-free survival (PFS) rate after treatment with rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) in patients with bulky stage II or stage III or IV diffuse large B-cell non-Hodgkin's lymphoma who remain positron emission tomography (PET)-positive after 3 courses of rituximab, cyclophosphamide, vincristine, doxorubicin hydrochloride, and prednisone.

Secondary

  • Determine the proportion of mid-treatment PET-positive patients who become PET-negative after 4 courses of R-ICE.
  • Determine the PFS of mid-treatment PET-negative patients treated with these regimens.
  • Determine the overall survival of patients treated with these regimens.
  • Determine the toxicity of these regimens in these patients.

OUTLINE:

  • Rituximab and Combination Chemotherapy (R-CHOP: R= Rituximab, C= Cyclophosphamide, H= Doxorubicin Hydrochloride (Hydroxydaunomycin), O= Vincristine Sulfate (Oncovin), P= Prednisone): Patients receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine IV on day 1, and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients undergo fludeoxyglucose F18 positron emission tomography (PET) scanning and conventional restaging during course 3. Based on the PET results, patients are assigned to 1 of 2 treatment groups.

    • Group I (PET negative): Patients receive 2 more courses of R-CHOP as above in the absence of disease progression or unacceptable toxicity.
    • Group II (PET positive): Patients receive Rituximab 375 mg/m2 IV Day 1, Ifosfamide 5000 mg/m2 IV over 24 hours Day 2, Carboplatin AUC 5 (max: 800 mg) IV Day 2, Etoposide 100 mg/m2 IV Days 1, 2, 3 (R-ICE), Mesna 5000 mg/m2 IV over 24 hours Day 2, and Filgrastim 5 mcg/kg/day subcutaneous (SC) Day 4 until absolute neutrophil count (ANC) recovery every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 10 years from the date of study entry.

ACCRUAL: A total of 100 patients were accrued for this study.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lymphoma
Intervention  ICMJE
  • Biological: filgrastim
    Given subcutaneously or intravenous bolus.
    Other Names:
    • G-CSF, Neupogen, recombinant-methionyl human granulocyte-colony stimulating
    • factor, granulocyte colony-stimulating factor, r-metHuG-CSF.
  • Biological: rituximab
    Given IV
    Other Name: IDEC-C2B8, Chimeric anti-CD20 monoclonal antibody, Rituxan.
  • Drug: carboplatin
    Given IV
    Other Name: CBDCA, Paraplatin, JM-8, NSC #241240.
  • Drug: cyclophosphamide
    Given IV
    Other Name: Cytoxan, Neosar, CTX, CPM.
  • Drug: doxorubicin hydrochloride
    Given IV
    Other Names:
    • Adriamycin, Rubex, Adriamycin RDF, Adriamycin PFS, hydroxydaunorubicin,
    • hydroxydaunomycin, ADR.
  • Drug: etoposide
    Given IV
    Other Name: VP-16, VePesid, epipodophyllotoxin
  • Drug: ifosfamide
    Given IV
    Other Name: Isophosphamide, Ifex , Mitoxan , Holoxan , Naxamide ' NSC # 109724.
  • Drug: prednisone
    Taken orally
    Other Name: Deltasone, Orasone, Medicorten, Panasol-S, Liquid-Pred, others.
  • Drug: vincristine
    Given IV
    Other Name: Oncovin, Vincasar PFS vincristine sulfate, VCR, leucocristine, LCR.
Study Arms  ICMJE
  • Experimental: Group I (PET negative)
    Patients receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine IV on day 1, and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Biological: rituximab
    • Drug: cyclophosphamide
    • Drug: doxorubicin hydrochloride
    • Drug: prednisone
    • Drug: vincristine
  • Experimental: Group II (PET positive)
    Patients receive R-ICE comprising rituximab IV on day 1, ifosfamide IV continuously over 24 hours and carboplatin IV over 30 minutes on day 2, and etoposide IV over 2 hours on days 1-3. Patients also receive filgrastim (G-CSF) subcutaneously once daily starting on day 4 and continuing until blood counts recover. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Biological: filgrastim
    • Biological: rituximab
    • Drug: carboplatin
    • Drug: cyclophosphamide
    • Drug: etoposide
    • Drug: ifosfamide
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 9, 2014)
100
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE March 2019
Actual Primary Completion Date June 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

INCLUSION CRITERIA:

  • Diffuse large B-cell non-Hodgkin's lymphoma

    • Bulky stage II (bulk defined as any lesion ≥ 10 cm) or stage III or IV disease
    • The following lymphoma types are excluded:

      • Primary central nervous system lymphoma
      • Transformed low-grade lymphoma (prior history of low-grade lymphoma or clear presence of low-grade lymphoma on histologic sections)
      • Primary mediastinal B-cell lymphoma or testicular lymphoma (consolidative radiotherapy is usually indicated)
      • Immunodeficiency-related lymphoma (i.e., after organ or bone marrow transplant)
  • Measurable disease

    • Patient must have at least one objective measurable disease site (i.e., measurable in at least 2 perpendicular parameters)
    • Measurable disease in the liver is required if the liver is the only site of lymphoma involvement
    • Abnormal positron emission tomography scans will not constitute evaluable disease, unless verified by CT scan or other appropriate imaging
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-3
  • For patients > 50 years of age, a normal ejection fraction by ECHO or Multigated Acquisition Scan (MUGA) is required within 6 weeks prior to registration
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count > 100,000/mm^3
  • Creatinine < 2.0 mg/dL
  • Bilirubin < 2 mg/dL (may be up to 3.0 mg/dL if due to liver involvement by lymphoma)

EXCLUSION CRITERIA:

  • Prior chemotherapy or radiation therapy for lymphoma
  • Prior anthracyclines or platinum compounds used as systemic chemotherapy
  • Prior radiation therapy to the mediastinum or to ≥ 25% of the bone marrow
  • Concurrent pentostatin or trastuzumab (Herceptin®)
  • Pregnant or nursing
  • Prior malignancy within the past 5 years unless it was in situ OR was treated with curative intent AND the patient has remained relapse-free
  • HIV positive
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00274924
Other Study ID Numbers  ICMJE CDR0000455012
U10CA021115 ( U.S. NIH Grant/Contract )
E3404 ( Other Identifier: Eastern Cooperative Oncology Group (ECOG) )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eastern Cooperative Oncology Group
Study Sponsor  ICMJE Eastern Cooperative Oncology Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Lode J. Swinnen, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
PRS Account Eastern Cooperative Oncology Group
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP