Rituximab and Combination Chemotherapy in Treating Patients With Non-Hodgkin's Lymphoma
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| ClinicalTrials.gov Identifier: NCT00278421 |
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Recruitment Status :
Completed
First Posted : January 18, 2006
Last Update Posted : March 11, 2021
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RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, 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. It is not yet known which schedule of rituximab and combination chemotherapy is more effective in treating non-Hodgkin's lymphoma.
PURPOSE: This randomized phase III trial is studying two different schedules of rituximab and combination chemotherapy to compare how well they work in treating patients with aggressive B-cell non-Hodgkin's lymphoma.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Lymphoma | Biological: rituximab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisone Drug: vincristine sulfate | Phase 3 |
OBJECTIVES:
Primary
- Compare the efficacy of 2 different schedules of immunochemotherapy comprising rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone in patients with previously untreated, low-risk, aggressive B-cell non-Hodgkin's lymphoma.
- Compare acute and chronic side effects in patients treated with these regimens.
- Compare time to treatment failure in patients treated with these regimens.
Secondary
- Compare the time to progression in patients treated with these regimens.
- Compare the overall and disease-free/relapse-free survival of patients treated with these regimens.
- Compare the complete response rate in patients treated with these regimens.
- Compare the tumor control in patients treated with these regimens.
- Compare the safety of these regimens in these patients.
- Compare the pharmacoeconomics of these regimens.
- Compare patient adherence to these regimens.
OUTLINE: This is an open-label, randomized, multicenter study. Patients are stratified according to participating center. Patients are randomized to 1 of 2 treatment arms.
All patients are given the option of receiving a 1-week course of pretreatment therapy comprising vincristine IV once on day -6 and oral prednisone once daily on days -6 to 0.
- Arm I: Patients receive R-CHOP immunochemotherapy comprising rituximab IV, cyclophosphamide IV over 15 minutes, doxorubicin hydrochloride IV, and vincristine IV on day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo restaging of their disease. Patients with disease progression proceed to salvage therapy off study. All other patients receive 3 more courses of R-CHOP.
- Arm II: Patients receive R-CHOP as in arm I. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo restaging of their disease. Patients with disease progression proceed to salvage therapy off study. All other patients receive 1 more course of R-CHOP followed by 2 courses of rituximab alone.
All patients undergo final restaging after 6 courses of rituximab. Patients with disease progression, stable disease, or partial response proceed to salvage therapy off study.
After completion of study treatment, patients are followed periodically for 5 years and then annually thereafter.
PROJECTED ACCRUAL: A total of 622 patients will be accrued for this study.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 592 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Randomized Study Comparing 4 and 6 Cycles of Chemotherapy With CHOP (Cyclophosphamide, Doxorubicin, Vincristine and Prednisone) at 21-day Intervals, Both With 6 Cycles of Immunotherapy With the Monoclonal Anti-CD20-Positive B-Cell Lymphoma Aged 18-60 Years Having no Risk Factor (Age-Adjusted IPI=0) and No Large Tumor Mass (Diameter <7,5cm) [FLYER 6-6-6-4 Study] |
| Study Start Date : | November 2005 |
| Actual Primary Completion Date : | August 2018 |
| Actual Study Completion Date : | August 2018 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Interventional: 6 R-CHOP-21
Arm I: Patients receive R-CHOP immunochemotherapy comprising rituximab IV, cyclophosphamide IV over 15 minutes, doxorubicin hydrochloride IV, and vincristine IV on day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo restaging of their disease. Patients with disease progression proceed to salvage therapy off study. All other patients receive 3 more courses of R-CHOP.
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Biological: rituximab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisone Drug: vincristine sulfate |
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Active Comparator: Interventional: 4 R-CHOP-21 + 2 x R
Arm II: Patients receive R-CHOP as in arm I. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo restaging of their disease. Patients with disease progression proceed to salvage therapy off study. All other patients receive 1 more course of R-CHOP followed by 2 courses of rituximab alone.
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Biological: rituximab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisone Drug: vincristine sulfate |
- Time to treatment failure (TTF) measured from day 1 of course 1 of Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (CHOP) therapy up to 3 years on study with life-long follow-up [ Time Frame: through study completion ]
- Complete response (CR) rate duration until first relapse [ Time Frame: through study completion ]
- Progression rate during treatment [ Time Frame: through study completion ]
- Survival [ Time Frame: through study completion ]
- Tumor control measured from day 1 of course 1 of CHOP therapy (non-tumor related events are censored) [ Time Frame: through study completion ]
- Disease-free survival measured from day 1 of course 1 of CHOP therapy [ Time Frame: through study completion ]
- Safety (adverse events, serious adverse events) assessed at 3 months after treatment [ Time Frame: through study completion ]
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| Ages Eligible for Study: | 18 Years to 60 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
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Histologically confirmed aggressive B-cell non-Hodgkin's lymphoma, including the following subtypes:
- Grade 3 follicular lymphoma
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Diffuse B-cell lymphoma, including diffuse large cell lymphoma with any of the following variants:
- Centroblastic
- Immunoblastic
- Plasmablastic
- Anaplastic large cell
- T-cell-rich B-cell lymphoma
- Primary effusion lymphoma
- Intravascular B-cell lymphoma
- Primary mediastinal B-cell lymphoma
- Burkitt's or Burkitt-like lymphoma
- Mantle cell lymphoma (blastoid)
- Aggressive marginal zone lymphoma (monocytoid)
- Previously untreated disease
- CD20-positive disease
- International Prognostic Index (IPI) score 0
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No bulky disease
- Largest single or conglomerate tumor < 7.5 cm in diameter
- No mucosa-associated lymphoid tissue (MALT) lymphoma
- No CNS involvement of lymphoma (intracerebral, meningeal, or intraspinal)
PATIENT CHARACTERISTICS:
- ECOG performance status 0-1
- Platelet count ≥ 100,000/mm^3
- WBC ≥ 2,500/mm^3
- Lactate dehydrogenase normal
- Not pregnant or lactating
- Fertile patients must use effective contraception during and for 1 year after study participation
- Negative pregnancy test
- No known hypersensitivity to the study medications
- No known HIV-positivity
- No active hepatitis infection
- No impaired left ventricular function
- No severe cardiac arrhythmias
- No other impaired organ function
- No other serious disorder
- No other malignancy within the past 5 years except carcinoma in situ or basal cell skin cancer
PRIOR CONCURRENT THERAPY:
- No prior chemotherapy or radiotherapy
- No prior immunosuppressive treatment with cytostatics
- No planned radiotherapy to extranodal involvement
- No concurrent participation in other treatment studies
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00278421
Show 78 study locations
| Study Chair: | Michael G.M. Pfreundschuh, MD † | Universitaetsklinikum des Saarlandes | |
| Study Director: | Viola Poeschel, MD | Study Office Homburg |
| Responsible Party: | German High-Grade Non-Hodgkin's Lymphoma Study Group |
| ClinicalTrials.gov Identifier: | NCT00278421 |
| Other Study ID Numbers: |
CDR0000459685 DSHNHL-2004-2 EU-205110 EUDRACT-2005-00521738 DSHNHL-FLYER-6664 |
| First Posted: | January 18, 2006 Key Record Dates |
| Last Update Posted: | March 11, 2021 |
| Last Verified: | March 2021 |
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contiguous stage II grade 3 follicular lymphoma noncontiguous stage II grade 3 follicular lymphoma stage I grade 3 follicular lymphoma contiguous stage II adult diffuse large cell lymphoma contiguous stage II adult diffuse mixed cell lymphoma noncontiguous stage II adult diffuse large cell lymphoma noncontiguous stage II adult diffuse mixed cell lymphoma stage I adult diffuse large cell lymphoma stage I adult diffuse mixed cell lymphoma nodal marginal zone B-cell lymphoma anaplastic large cell lymphoma contiguous stage II adult immunoblastic large cell lymphoma noncontiguous stage II adult immunoblastic large cell lymphoma stage I adult immunoblastic large cell lymphoma contiguous stage II adult Burkitt lymphoma |
contiguous stage II mantle cell lymphoma noncontiguous stage II adult Burkitt lymphoma noncontiguous stage II mantle cell lymphoma stage I adult Burkitt lymphoma stage I mantle cell lymphoma contiguous stage II marginal zone lymphoma noncontiguous stage II marginal zone lymphoma stage I marginal zone lymphoma stage III marginal zone lymphoma stage IV marginal zone lymphoma stage III adult Burkitt lymphoma stage III adult diffuse large cell lymphoma stage III adult diffuse mixed cell lymphoma stage III adult immunoblastic large cell lymphoma stage III grade 3 follicular lymphoma |
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Lymphoma Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Prednisone Cyclophosphamide Rituximab Doxorubicin Liposomal doxorubicin Vincristine Immunosuppressive Agents Immunologic Factors |
Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antineoplastic Agents, Immunological Antibiotics, Antineoplastic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Anti-Inflammatory Agents Glucocorticoids Hormones |