Rituximab and Combination Chemotherapy in Treating Patients With Non-Hodgkin's Lymphoma

Conditions

Lymphoma

Keywords

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, stage III mantle cell lymphoma, stage IV adult Burkitt lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV grade 3 follicular lymphoma, stage IV mantle cell lymphoma

Brief summary

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.

Detailed description

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.

Konstantinos Christofyllakis, Vadim Lesan, Moritz Bewarder, Bettina Altmann, Marita Ziepert et al. (14 authors)

Blood2025-11-03

10.1182/blood-2025-469

Adding Etoposide to R-CHOP (R-CHOEP) Does Not Significantly Increase the Risk of Secondary Neoplasms in Patients with Aggressive B-Cell Lymphoma - Results from Randomized Phase 3 Trials of the German Lymphoma Alliance (GLA)

Fabian Frontzek, Marita Ziepert, Maike Nickelsen, Bettina Altmann, Bertram Glaß et al. (21 authors)

Blood2020-11-04

10.1182/blood-2020-138412

Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER): a randomised, phase 3, non-inferiority trial.

Poeschel V, Held G, Ziepert M, Witzens-Harig M, Holte H, Thurner L, Borchmann P, Viardot A, Soekler M, Keller U, Schmidt C, Truemper L, Mahlberg R, Marks R, Hoeffkes HG, Metzner B, Dierlamm J, Frickhofen N, Haenel M, Neubauer A, Kneba M, Merli F, Tucci A, de Nully Brown P, Federico M, Lengfelder E, di Rocco A, Trappe R, Rosenwald A, Berdel C, Maisenhoelder M, Shpilberg O, Amam J, Christofyllakis K, Hartmann F, Murawski N, Stilgenbauer S, Nickelsen M, Wulf G, Glass B, Schmitz N, Altmann B, Loeffler M, Pfreundschuh M, FLYER Trial Investigators, German Lymphoma Alliance.

2019-12-01164 citations

10.1016/s0140-6736(19)33008-9

Guidelines for the management of diffuse large B‐cell lymphoma

Sridhar Chaganti, Tim Illidge, Sally F. Barrington, Pam McKay, Kim Linton et al. (10 authors)

British Journal of Haematology2016-05-16163 citations

10.1111/bjh.14136

Interventions

DRUGvincristine sulfate

DRUGdoxorubicin hydrochloride

DRUGprednisone

BIOLOGICALrituximab

DRUGcyclophosphamide

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 60 Years

Healthy volunteers

No

Inclusion criteria

DISEASE CHARACTERISTICS: * Histologically confirmed aggressive B-cell non-Hodgkin's lymphoma, including the following subtypes: * Grade 3 follicular lymphoma * 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 * 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

Design outcomes

Primary

Measure	Time frame
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	through study completion

Secondary

Measure	Time frame
Progression rate during treatment	through study completion
Survival	through study completion
Complete response (CR) rate duration until first relapse	through study completion
Disease-free survival measured from day 1 of course 1 of CHOP therapy	through study completion
Safety (adverse events, serious adverse events) assessed at 3 months after treatment	through study completion
Tumor control measured from day 1 of course 1 of CHOP therapy (non-tumor related events are censored)	through study completion

Countries

Germany, Israel, Italy

Outcome results

None listed