Combination Chemotherapy With or Without Rituximab in Tre... | NCT00052936 | Trialant
NCT00052936
Sponsor
German High-Grade Non-Hodgkin's Lymphoma Study Group
Status
Completed
Last Update Posted
May 18, 2021Actual
Enrollment
1,506Actual
Phase
Phase 3
Conditions
Lymphoma
Interventions
filgrastim
rituximab
CHOP regimen
cyclophosphamide
doxorubicin hydrochloride
prednisone
vincristine sulfate
radiation therapy
Countries
Germany
Switzerland
Protocol Section
Identification Module
NCT ID
NCT00052936
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
CDR0000269015
Secondary IDs
ID
Type
Description
Link
DSHNHL-1999-1A
Other Grant/Funding Number
Deutsche Krebshilfe
EU-20243
Other Identifier
Ethikkommission der Ärztekammer des Saarlandes [85/99]
Brief Title
Combination Chemotherapy With or Without Rituximab in Treating Older Patients With Non-Hodgkin's Lymphoma
Official Title
Randomised Study Comparing 6 And 8 Cycles Of Chemotherapy With CHOP ( Cyclophosphamide, Doxorubicin, Vincristine And Prednisone) At 14-Day Intervals (CHOP-14), Both With Or Without The Monoclonal Anti-CD20 Antibody Rituximab In Patients Aged 61 To 80 Years With Aggressive Non-Hodgkin's Lymphoma
Acronym
Not provided
Organization
Universität des SaarlandesOTHER
Status Module
Record Verification Date
May 2021
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jan 2001
Primary Completion Date
Aug 5, 2010Actual
Completion Date
Aug 5, 2010Actual
First Submitted Date
Jan 24, 2003
First Submission Date that Met QC Criteria
Jan 26, 2003
First Posted Date
Jan 27, 2003Estimated
Results Waived
Not provided
Results First Submitted Date
Not provided
Results First Submitted that Met QC Criteria
Not provided
Results First Posted Date
Not provided
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
May 14, 2021
Last Update Posted Date
May 18, 2021Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
German High-Grade Non-Hodgkin's Lymphoma Study GroupOTHER
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known whether combination chemotherapy is more effective with or without rituximab in treating aggressive non-Hodgkin's lymphoma.
PURPOSE: This randomized phase III trial is studying how well giving cyclophosphamide, doxorubicin, vincristine, and prednisone together with or without rituximab works in treating older patients who have aggressive non-Hodgkin's lymphoma. (This trial is no longer randomized as of 6/2005).
Detailed Description
OBJECTIVES:
Primary
Compare the efficacy of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with vs without rituximab in elderly patients with aggressive non-Hodgkin's lymphoma.
Compare the efficacy of 6 vs 8 courses of CHOP chemotherapy in patients treated with these regimens.
Compare the rate of complete remission, rate of primary progression, tumor control, disease-free survival, overall survival, and relapse after radiotherapy in patients treated with these regimens.
Compare the safety and side effects of these regimens in these patients.
Secondary
Compare short-term and long-term side effects of these regimens in these patients.
Compare quality of life of patients treated with these regimens.
Compare the cost of these regimens in these patients.
Determine relapse in patients treated with these regimens who received involved-field radiotherapy.
OUTLINE: This is a randomized (randomized part of study completed as of 6/2005), open-label, multicenter study. Patients are stratified according to participating center, value for serum lactic dehydrogenase (no greater than upper limit of normal [ULN] vs greater than ULN), bulky disease present (no vs yes), stage (I or II vs III or IV), general ECOG status of patient (0 or 1 vs 2), and age (61 to 70 vs 71-80). Patients are randomized to 1 of 4 treatment arms. Patients with CD20-negative lymphoma are randomized to arms I or II only.
Prephase treatment:Patients receive vincristine IV on day -6 and prednisone on day -6 to day 0 before initiating CHOP chemotherapy.
Arm I (closed to accrual as of 7/25/2005): Patients receive standard CHOP chemotherapy comprising cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 and oral prednisone on days 1-5. Patients also receive filgrastim (G-CSF) subcutaneously once daily on days 6-12 of each CHOP course. Treatment repeats every 2 weeks for 6 courses.
Arm II (closed to accrual as of 7/25/2005): Patients receive standard CHOP chemotherapy and G-CSF as in arm I for a total of 8 courses.
Arm III: Patients receive standard CHOP chemotherapy and G-CSF as in arm I. Patients also receive rituximab IV before CHOP every 2 weeks for a total of 8 courses.
Arm IV (closed to accrual as of 7/25/2005): Patients receive standard CHOP chemotherapy and G-CSF as in arm II. Patients also receive rituximab IV before CHOP every 2 weeks for a total of 8 courses.
In all arms, treatment continues in the absence of disease progression or unacceptable toxicity.
Beginning 3-6 weeks after completion of the last chemotherapy course, after complete recovery of bone marrow, and after complete remision of mucositis, patients with sites of initial bulky disease or extranodal involvement undergo radiotherapy 5 times a week for 4 weeks.
Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
PROJECTED ACCRUAL: Approximately 1580 patients will be accrued for this study within 5 years.
Conditions Module
Conditions
Lymphoma
Keywords
anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
stage III grade 1 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III grade 2 follicular lymphoma
stage I adult T-cell leukemia/lymphoma
stage II adult T-cell leukemia/lymphoma
stage III adult T-cell leukemia/lymphoma
stage IV adult T-cell leukemia/lymphoma
contiguous stage II adult lymphoblastic lymphoma
noncontiguous stage II adult lymphoblastic lymphoma
stage I adult lymphoblastic lymphoma
stage III adult lymphoblastic lymphoma
stage IV adult lymphoblastic lymphoma
contiguous stage II adult diffuse large cell lymphoma
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
1,506Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
S6
Experimental
6x CHOP-14
Biological: filgrastim
Drug: CHOP regimen
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: prednisone
Drug: vincristine sulfate
Radiation: radiation therapy
R6
Experimental
6x CHOP-14 + 8x Rituximab
Biological: filgrastim
Biological: rituximab
Drug: CHOP regimen
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: prednisone
Drug: vincristine sulfate
Radiation: radiation therapy
S8
Experimental
8x CHOP-14
Biological: filgrastim
Drug: CHOP regimen
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: prednisone
Drug: vincristine sulfate
Radiation: radiation therapy
R8
Experimental
8x CHOP-14 + 8x Rituximab
Biological: filgrastim
Biological: rituximab
Drug: CHOP regimen
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: prednisone
Drug: vincristine sulfate
Radiation: radiation therapy
Interventions
Name
Type
Description
Arm Group Labels
Other Names
filgrastim
Biological
R6
R8
S6
S8
rituximab
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Time to treatment failure at 3 years within the study and then periodically after study completion
3 years within the study and then periodically after study completion
Secondary Outcomes
Measure
Description
Time Frame
Complete response rate at 3 years within the study and then periodically after study completion
3 years within the study and then periodically after
Progression rate
3 years within the study and then periodically after
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
DISEASE CHARACTERISTICS:
Histologically confirmed aggressive non-Hodgkin's lymphoma (NHL) by an excisional biopsy of a lymph node or an extensive biopsy of an extranodal involvement (if there is no lymph node involvement)
CD20^+ B-cell lymphoma or CD20^- B-cell and T-cell lymphoma allowed
B-cell NHL including the following:
Stage III follicular lymphoma
Stage III follicular lymphoma and diffuse B-cell lymphoma
Lymphoblastic precursor B-cell lymphoma
Diffuse large cell B-cell lymphoma
Centroblastic
Immunoblastic
Plasmablastic
Anaplastic large cell
T-cell-rich B-cell lymphoma
Primary effusion lymphoma
Intravasal B-cell lymphoma
Primary mediastinal B-cell lymphoma
Mantle zone lymphoma, blastoid
Burkitt's lymphoma
Burkitt-like lymphoma
Aggressive marginal zone lymphoma (monocytoid)
T-cell NHL including the following:
Lymphoblastic precursor T-cell lymphoma
Peripheral T-cell lymphoma (PTCL) not otherwise specified (NOS)
Lennert's lymphoma
T-zone lymphoma
T-cell lymphoma of the angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) type
Anaplastic large cell lymphoma
ALK^+
ALK^-
Extranodal NK/T-cell lymphoma, nasal type
Intestinal T/NK-cell lymphoma (with or without enteropathy)
Hepatosplenic gamma-delta lymphoma
Subcutaneous panniculitis-like PTCL
Aggressive T/NK PTCL
Anaplastic large-cell NHL, NOS
Bone marrow involvement no more than 25%
No lymphoma that is clearly restricted to the CNS or originating from the gastrointestinal tract
PATIENT CHARACTERISTICS:
Age
61 to 80
Performance status
ECOG 0-2 OR
Karnofsky 60-100%
Life expectancy
Not specified
Hematopoietic
WBC at least 2,500/mm^3
Platelet count at least 100,000/mm^3
Hepatic
Bilirubin no greater than 2 times upper limit of normal (ULN)
No active hepatitis infection
Renal
Creatinine no greater than 2 times ULN
Cardiovascular
No Canadian Cardiovascular Society class III or IV angina pectoris
No New York Heart Association class III or IV cardiac failure
Ejection fraction at least 50%
Fractional shortenings at least 25% by echocardiography or nuclear medicine examination
Pulmonary
FEV1 at least 50%
Diffusion capacity at least 50%
Other
No uncontrolled diabetes mellitus
No known hypersensitivity to any study medications
No other concurrent malignancy
HIV negative
PRIOR CONCURRENT THERAPY:
Biologic therapy
Not specified
Chemotherapy
No prior chemotherapy
Endocrine therapy
Not specified
Radiotherapy
No prior radiotherapy
Surgery
Not specified
Other
Must not have already initiated lymphoma therapy (except for the prephase treatment specified for this study)
No other concurrent lymphoma therapy
No concurrent participation in another treatment study
Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trumper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, Schmitz N, Ruebe C, Feller AC, Loeffler M; German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008 Feb;9(2):105-16. doi: 10.1016/S1470-2045(08)70002-0. Epub 2008 Jan 15.
Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
Ulm
89081
Germany
Ev. Hospital Unna
Unna
59403
Germany
St. Marienhospital - Vechta
Vechta
49377
Germany
Municipal Hospital Complex
Villingen-Schwenningen
D-78045
Germany
Regional Hospital Waldbrol
Waldbröl
51545
Germany
Evangelisches Krankenhaus Essen Werden
Werden
45239
Germany
Hospital Wetzler
Wetzlar
35578
Germany
Deutsche Klinik fuer Diagnostik
Wiesbaden
65191
Germany
Dr. Horst-Schmidt-Kliniken
Wiesbaden
65199
Germany
Ev. Hospital Witten-Herdecke
Witten
58455
Germany
Kliniken St. Antonius
Wuppertal
42283
Germany
University Wurzburg
Würzburg
97070
Germany
Municipal Hospital Complex Zwickau
Zwickau
D-08060
Germany
City Hospital Triemli
Zurich
8063
Switzerland
UniversitaetsSpital Zuerich
Zurich
8091
Switzerland
Derived
Christofyllakis K, Kaddu-Mulindwa D, Lesan V, Rixecker T, Kos IA, Held G, Regitz E, Pfreundschuh M, Bittenbring JT, Thurner L, Poeschel V, Ziepert M, Altmann B, Bewarder M. An inherited genetic variant of the CEP72 gene is associated with the development of vincristine-induced peripheral neuropathy in female patients with aggressive B-cell lymphoma. Ann Hematol. 2024 Nov;103(11):4599-4606. doi: 10.1007/s00277-024-05973-9. Epub 2024 Sep 4.
Kuhnl A, Cunningham D, Counsell N, Hawkes EA, Qian W, Smith P, Chadwick N, Lawrie A, Mouncey P, Jack A, Pocock C, Ardeshna KM, Radford J, McMillan A, Davies J, Turner D, Kruger A, Johnson PW, Gambell J, Rosenwald A, Ott G, Horn H, Ziepert M, Pfreundschuh M, Linch D. Outcome of elderly patients with diffuse large B-cell lymphoma treated with R-CHOP: results from the UK NCRI R-CHOP14v21 trial with combined analysis of molecular characteristics with the DSHNHL RICOVER-60 trial. Ann Oncol. 2017 Jul 1;28(7):1540-1546. doi: 10.1093/annonc/mdx128.
Pfreundschuh M, Poeschel V, Zeynalova S, Hanel M, Held G, Schmitz N, Viardot A, Dreyling MH, Hallek M, Mueller C, Wiesen MH, Witzens-Harig M, Truemper L, Keller U, Rixecker T, Zwick C, Murawski N. Optimization of rituximab for the treatment of diffuse large B-cell lymphoma (II): extended rituximab exposure time in the SMARTE-R-CHOP-14 trial of the german high-grade non-Hodgkin lymphoma study group. J Clin Oncol. 2014 Dec 20;32(36):4127-33. doi: 10.1200/JCO.2013.54.6861. Epub 2014 Nov 17.
Bittenbring JT, Neumann F, Altmann B, Achenbach M, Reichrath J, Ziepert M, Geisel J, Regitz E, Held G, Pfreundschuh M. Vitamin D deficiency impairs rituximab-mediated cellular cytotoxicity and outcome of patients with diffuse large B-cell lymphoma treated with but not without rituximab. J Clin Oncol. 2014 Oct 10;32(29):3242-8. doi: 10.1200/JCO.2013.53.4537. Epub 2014 Aug 18.
Held G, Murawski N, Ziepert M, Fleckenstein J, Poschel V, Zwick C, Bittenbring J, Hanel M, Wilhelm S, Schubert J, Schmitz N, Loffler M, Rube C, Pfreundschuh M. Role of radiotherapy to bulky disease in elderly patients with aggressive B-cell lymphoma. J Clin Oncol. 2014 Apr 10;32(11):1112-8. doi: 10.1200/JCO.2013.51.4505. Epub 2014 Feb 3.
Horn H, Ziepert M, Becher C, Barth TF, Bernd HW, Feller AC, Klapper W, Hummel M, Stein H, Hansmann ML, Schmelter C, Moller P, Cogliatti S, Pfreundschuh M, Schmitz N, Trumper L, Siebert R, Loeffler M, Rosenwald A, Ott G; German High-Grade Non-Hodgkin Lymphoma Study Group. MYC status in concert with BCL2 and BCL6 expression predicts outcome in diffuse large B-cell lymphoma. Blood. 2013 Mar 21;121(12):2253-63. doi: 10.1182/blood-2012-06-435842. Epub 2013 Jan 18.
Muller C, Murawski N, Wiesen MH, Held G, Poeschel V, Zeynalova S, Wenger M, Nickenig C, Peter N, Lengfelder E, Metzner B, Rixecker T, Zwick C, Pfreundschuh M, Reiser M. The role of sex and weight on rituximab clearance and serum elimination half-life in elderly patients with DLBCL. Blood. 2012 Apr 5;119(14):3276-84. doi: 10.1182/blood-2011-09-380949. Epub 2012 Feb 15.