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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT00274924
First received: January 10, 2006
Last updated: April 10, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Lymphoma
Biological: filgrastim
Biological: rituximab
Drug: carboplatin
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: ifosfamide
Drug: prednisone
Drug: vincristine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Response-Adapted Therapy for Aggressive Non-Hodgkin's Lymphomas Based on Early [18F] FDG-PET Scanning

Resource links provided by NLM:


Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    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.


Enrollment: 100
Study Start Date: April 2006
Estimated Study Completion Date: March 2019
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Biological: rituximab
Given IV
Other Name: IDEC-C2B8, Chimeric anti-CD20 monoclonal antibody, Rituxan.
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: 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.
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.
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: etoposide
Given IV
Other Name: VP-16, VePesid, epipodophyllotoxin
Drug: ifosfamide
Given IV
Other Name: Isophosphamide, Ifex , Mitoxan , Holoxan , Naxamide ' NSC # 109724.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00274924

  Show 104 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Study Chair: Lode J. Swinnen, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
Horning SJ, Juweid ME, Schoder H, et al.: Interim positron emission tomography (PET) in diffuse large B-cell lymphoma: independent expert nuclear medicine evaluation of ECOG 3404. [Abstract] Blood 112 (11): A-372, 2008.

Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00274924     History of Changes
Other Study ID Numbers: CDR0000455012, U10CA021115, E3404
Study First Received: January 10, 2006
Results First Received: January 9, 2014
Last Updated: April 10, 2014
Health Authority: United States: Federal Government

Keywords provided by Eastern Cooperative Oncology Group:
contiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Carboplatin
Cyclophosphamide
Doxorubicin
Etoposide
Ifosfamide
Lenograstim
Liposomal doxorubicin
Prednisone
Rituximab
Vincristine
Adjuvants, Immunologic
Alkylating Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014