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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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT00274924
First received: January 10, 2006
Last updated: December 12, 2012
Last verified: December 2012
History of Changes
  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 sulfate
 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 [F] F.G.-PET Scanning

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • 2- year progression-free survival (PFS) [ Time Frame: Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually for 5 years. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • PFS among patients who are PET-negative after 3 courses of treatment [ Time Frame: Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually for 5 years. ] [ Designated as safety issue: No ]
  • Proportion of PET-positive patients who become PET-negative after 4 courses of treatment [ Time Frame: Assessed between 8-9 weeks from the start of R-CHOP therapy, and again at the end of all study therapy ] [ Designated as safety issue: No ]
    PET scan and conventional restaging


Estimated Enrollment: 99
Study Start Date: April 2006
Estimated Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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
Drug: cyclophosphamide
Given IV (prednisone given orally)
Drug: doxorubicin hydrochloride
Given IV (prednisone given orally)
Drug: prednisone
Given IV (prednisone given orally)
Drug: vincristine sulfate
Given IV (prednisone given orally)
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
Biological: rituximab
Given IV
Drug: carboplatin
Given IV
Drug: cyclophosphamide
Given IV (prednisone given orally)
Drug: etoposide
Given IV
Drug: ifosfamide
Given IV

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 CHOP chemotherapy (R-CHOP): 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 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.

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

PROJECTED ACCRUAL: A total of 99 patients will be accrued for this study.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-3
  • For patients > 50 years of age, a normal ejection fraction by ECHO or 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)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use an accepted and effective method of contraception
  • No 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 negative NOTE: *Unless abnormal due to lymphoma

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy or radiation therapy for lymphoma
  • No prior anthracyclines or platinum compounds used as systemic chemotherapy
  • No prior radiation therapy to the mediastinum or to ≥ 25% of the bone marrow
  • No concurrent pentostatin or trastuzumab (Herceptin®)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00274924

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

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

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
Last Updated: December 12, 2012
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, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Rituximab
Ifosfamide
Isophosphamide mustard
Etoposide phosphate
Doxorubicin
 Etoposide
Prednisone
Vincristine
Carboplatin
Lenograstim
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on May 19, 2013