Study of the Combination of Rituximab, Cyclophosphamide, Doxorubicin, VELCADE, and Prednisone or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Newly Diagnosed Mantle Cell Lymphoma
Sponsor
Millennium Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT00722137
Collaborator
Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (Industry)
487
150
2
109.5
3.2
0
Study Details
Study Description
Brief Summary
This is a randomized, open-label, multicenter, prospective study to compare the efficacy and safety of the combination of VcR-CAP to that of R-CHOP in participants who have newly diagnosed mantle cell lymphoma grade II, III or IV and who are ineligible to undergo bone marrow transplantation.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
The drug being tested in this study were combination of VcR-CAP and R-CHOP. Combination of VcR-CAP and R-CHOP is being tested to treat people who had mantle cell lymphoma (MCL).
The study enrolled 487 patients. Participants were randomly assigned (by chance, like flipping a coin) to one of the two treatment groups in a 1:1 ratio:
Treatment Group A (VcR-CAP) Treatment Group B (R-CHOP)
The study included a screening phase, a treatment phase, a short-term follow-up phase, and a long-term follow-up phase. The screening phase was up to 28 days (56 days for bone marrow evaluation) prior to randomization.
This multi-center trial was conducted worldwide. The total study duration from randomization of the first patient until the last progression-free survival (PFS) event required for the final analysis was expected to be approximately 42 months (24 months for enrollment and 18 months for follow-up) and survival follow-up every 12 weeks until death.
Study Design
Study Type:
Interventional
Actual Enrollment
:
487 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized, Open-Label, Multicenter Phase 3 Study of the Combination of Rituximab, Cyclophosphamide, Doxorubicin, VELCADE, and Prednisone (VcR-CAP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Patients With Newly Diagnosed Mantle Cell Lymphoma Who Are Not Eligible for a Bone Marrow Transplant
Actual Study Start Date
:
May 1, 2008
Actual Primary Completion Date
:
Jan 1, 2014
Actual Study Completion Date
:
Jun 17, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: R-CHOP Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, Vincristine 1.4 mg/m^2, and Prednisone 100 mg/m^2 |
Drug: Rituximab 375 mg/m^2
Intravenous rituximab 375 mg/m^2 on Day 1 of a 21-day (3 week) cycle for 6 cycles.
Drug: Cyclophosphamide 750 mg/m^2
Intravenous cyclophosphamide 750 mg/m^2 on Day 1 of a 21-day (3 week) cycle for 6 cycles
Drug: Doxorubicin 50 mg/m^2
Intravenous doxorubicin 50 mg/m^2 on Day 1 of a 21-day (3 week) cycle for 6 cycles
Drug: Prednisone 100 mg/m^2
Oral prednisone 100 mg/m^2 on Day 1 to Day 5 of a 21-day (3 week) cycle for 6 cycles
Drug: Vincristine 1.4 mg/m^2
Intravenous vincristine 1.4 mg/m^2 on Day 1of a 21-day (3 week) cycle for 6 cycles. Maximum of 2 mg. Participants could receive 8 cycles if a response was initially documented at the Cycle 6 assessment.
|
| Experimental: VcR-CAP Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, VELCADE 1.3 mg/m^2, and Prednisone 100 mg/m^2 |
Drug: Rituximab 375 mg/m^2
Intravenous rituximab 375 mg/m^2 on Day 1 of a 21-day (3 week) cycle for 6 cycles.
Drug: Cyclophosphamide 750 mg/m^2
Intravenous cyclophosphamide 750 mg/m^2 on Day 1 of a 21-day (3 week) cycle for 6 cycles
Drug: Doxorubicin 50 mg/m^2
Intravenous doxorubicin 50 mg/m^2 on Day 1 of a 21-day (3 week) cycle for 6 cycles
Drug: VELCADE 1.3 mg/m^2
Intravenous VELCADE 1.3 mg/m^2 on Days 1,4,8, and 11of a 21-day (3 week) cycle for 6 cycles
Drug: Prednisone 100 mg/m^2
Oral prednisone 100 mg/m^2 on Day 1 to Day 5 of a 21-day (3 week) cycle for 6 cycles
|
Outcome Measures
Primary Outcome Measures
- Progression Free Survival (PFS) [Median duration of follow-up of 40 months]
PFS was defined as the interval between the date of randomization and the date of progressive disease (PD) or death, whichever occurred first. PD was based on the assessment of an Independent Review Committee.
Secondary Outcome Measures
- Time to Progression (TTP) [Median duration of follow-up of 40 months]
Time to progression was defined as the duration from the date of randomization until the date of first documented evidence of progressive disease (PD) or date of relapse for subjects who experienced complete response (CR) or complete response, unconfirmed (CRu). PD and response were based on the assessment of an Independent Review Committee.
- Duration of Response [Median duration of follow-up of 40 months]
The duration of treatment response was defined as the time from the date of the first response to the date of PD or death due to PD for those participants with a best response of CR, CRu, or PR as determined by the Independent Review Committee. The duration of response for complete responders was defined as the time from the date of the first response to the date of PD or death due to PD for those participants with a best response of CR or CRu verified by bone marrow and lactate dehydrogenase (LDH).
- Time to Next Anti-lymphoma Treatment (TTNT) [: Median duration of follow-up of 40 months]
The time to next anti-lymphomatreatment was measured from the date of initiation of study treatment as per protocol to the start date of new anti-lymphoma treatment. Death due to disease progression prior to subsequent therapy was considered as an event. Otherwise, time to next anti lymphoma treatment was censored at the date of death or the last date known to be alive.
- Treatment-free Interval (TFI) [Median duration of follow-up of 40 months]
The TFI was defined as the duration from the date of last dose plus 1 day to the start date of the new treatment. Death due to disease progression prior to subsequent therapy was considered as an event. Otherwise, treatment-free interval was censored at the date of death or the last date known to be alive.
- Overall Response Rate (ORR) [Median duration of follow-up of 40 months]
ORR was defined as complete response (CR) + complete response, unconfirmed (CRu) + partial response (PR) as determined by the Independent Review Committee. Response assessment was carried out every 6 weeks for 18 weeks; thereafter, every 8 weeks until PD/initiation of alternate therapy/withdrawal from study/death.
- Overall Complete Response (CR + CRu) [Median duration of follow-up of 40 months]
Overall complete response was defined as the number of participants with complete response (CR) and those with unconfirmed complete response (CRu). Response assessment was carried out every 6 weeks for 18 weeks; thereafter, every 8 weeks until PD/initiation of alternate therapy/withdrawal from study/death.
- Overall Survival (OS) [Median duration of follow-up of 40 months]
OS was measured from the date of randomization to the date of the participant's death. If the participant was alive or the vital status was unknown, OS was censored at the date that the subject was last known to be alive.
- 18-Month Survival [Up to month 18 from the time of randomization]
18-month survival was defined as the estimated probability of survival at 18 months (Kaplan-Meier estimate).
- Overall Survival (OS) in Long Term Follow-up Period [Up to 107.4 months]
OS was measured from the date of randomization to the date of the participant's death. If the participant was alive or the vital status was unknown, OS was censored at the date that the subject was last known to be alive.
- Number of Participants Experiencing an Adverse Event (AE) [Up to 107.4 months]
An AE was defined as any untoward medical occurrence associated with the use of a drug, whether or not considered drug related. AEs were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 8 cycles (24 weeks) and AEs were collected for up to 30 days following the last dose of study drug.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Male or female patients 18 years or older (the patient must be at least the legal age limit to be able to give informed consent within the jurisdiction the study is taking place)
-
Diagnosis of mantle cell lymphoma MCL (Stage II, III or IV) as evidenced by lymph node histology and either expression of cyclin D1 (in association with CD20 and CD5) or evidence of t(11;14) translocation, such as by cytogenetics, fluorescent in situ hybridization (FISH) or polymerase chain reaction (PCR). Patients with a diagnosis of Stage I MCL will not be permitted to enter study.
-
Paraffin embedded biopsy tissue block (preferably of lymph node origin) must be sent to the central laboratory for confirmation of MCL diagnosis prior to randomization. In China, a paraffin embedded lymph node biopsy tissue block must be sent for central confirmation of sample adequacy, prior to randomization
-
At least 1 measurable site of disease
-
No prior therapies for MCL
-
Not eligible for bone marrow transplantation as assessed by the treating physician (e.g., age or the presence of co-morbid conditions that may have a negative impact on the tolerability to transplantation).
-
Eastern Cooperative Oncology Group ECOG status ≤2
-
Absolute neutrophil count (ANC) ≥1500 cells/µL,
-
Platelets ≥100,000 cells/µL or ≥75,000 cells/µL if thrombocytopenia is considered by the investigator to be secondary to MCL (e.g., due to bone marrow infiltration or sequestration from splenomegaly).
-
Alanine transaminase ≤3 x upper limit of normal (ULN)
-
Aspartate transaminase ≤3 x ULN
-
Total bilirubin ≤1.5 x ULN,
-
Calculated creatinine clearance ≥20 mL/min.
-
Female patients must be post menopausal for at least 1 year (must not have had a natural menses for at least 12 months), surgically sterile, or practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) and have a negative serum βHCG or urine pregnancy test at screening. They must also be prepared to continue birth control measures for at least 6 months after terminating treatment.
-
Male patients must agree to use an acceptable method of contraception (for themselves or female partners as listed above) for the duration of the study.
-
All patients (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
-
In order to participate in the pharmacogenomics component of this study, patients (or their legally acceptable representative) must have signed the informed consent form for pharmacogenomics research indicating willingness to participate in the pharmacogenomics component of the study. Acquisition of tumor sample collections is required for all patients (where available); all other sample collections are optional
Exclusion Criteria:
-
Prior treatment with VELCADE
-
Prior antineoplastic (including unconjugated therapeutic antibodies), experimental or radiation therapy, radioimmunoconjugates or toxin immunoconjugates for the treatment of MCL. In the event that a patient has received doxorubicin for the treatment of any condition, other than MCL, the maximum dose and exposure received prior to entry into this study should not exceed 150 mg/m2.
-
short course (maximum of 10 days, not exceeding 100 mg/day) prednisone or equivalent steroids are allowed to treat symptoms in patients with advanced disease who enter the screening phase and are waiting to be randomized.
-
Major surgery (at the discretion of the treating physician and in consultation with the sponsor's medical monitor) within 2 weeks before randomization
-
Peripheral neuropathy or neuropathic pain of Grade 2 or worse (as per the investigators assessment)
-
Diagnosed or treated for a malignancy other than MCL within 1 year of randomization, or who were previously diagnosed with a malignancy other than MCL and have any radiographic or biochemical marker evidence of malignancy. Patients with completely resected basal cell carcinoma, squamous cell carcinoma of the skin, or in situ malignancy are not excluded.
-
Active systemic infection requiring treatment and patients with known diagnosis of human immunodeficiency virus HIV or active hepatitis B (carriers of hepatitis B are permitted to enter study)
-
History of allergic reaction attributable to compounds containing boron, mannitol, or hydroxybenzoates
-
Known anaphylaxis or immunoglobulin E (IgE)-mediated hypersensitivity to murine proteins or to any component of rituximab including polysorbate 80 and sodium citrate dihydrate
-
Female or male patients of child-bearing potential who will not use adequate contraception during the course of the study.
-
Serious medical (e.g., pericardial disease, cardiac failure [New York Heart Association; NYHA Class III or IV, Attachment 12 or left ventricular ejection fraction; LVEF <50%], active peptic ulceration, uncontrolled diabetes mellitus, or acute diffuse infiltrative pulmonary disease), or psychiatric illness likely to interfere with participation in this clinical study
-
Concurrent treatment with another investigational agent.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | St. Francis Hosptial and Medical Center | Hartford | Connecticut | United States | 06105 |
| 2 | Center for Cancer Care at Goshen Hospital | Goshen | Indiana | United States | 46526 |
| 3 | Sinai Hospital | Baltimore | Maryland | United States | 21215 |
| 4 | Capitol Comp. Cancer Center | Jefferson City | Missouri | United States | 65109 |
| 5 | Nebraska Cancer Specialists | Omaha | Nebraska | United States | 68114 |
| 6 | Hematology-Oncology Associates of Northern NJ | Morristown | New Jersey | United States | 07960 |
| 7 | Legacy Pharma Research | Bismarck | North Dakota | United States | 58501 |
| 8 | Division of Hematology and Oncology Vanderbilt University | Nashville | Tennessee | United States | 37232 |
| 9 | Cancer Outreach Associates, PC | Abingdon | Virginia | United States | 24211 |
| 10 | St.Johanns Spital/Landeskrankenhaus Salzburg | Salzburg | Austria | ||
| 11 | Allgemeines Krankenhaus der Stadt Wien | Wien | Austria | ||
| 12 | AZ Stuivenberg Oncologie/ Hematologie | Antwerpen | Belgium | ||
| 13 | AZ St Jan AV | Brugge | Belgium | ||
| 14 | UZ Brussel Department Medical Oncology | Brussels | Belgium | ||
| 15 | UZA Hematologie, 1e verdiep | Edegem | Belgium | ||
| 16 | Universitair Ziekenhuis Gent - UZ GENT, Hematologie, 9K12IE 9de verdiep- polikliniek Hematologie | Gent | Belgium | ||
| 17 | UZ Leuven Gasthuisberg Hematologie | Leuven | Belgium | ||
| 18 | C.H.R. Citadelle | Liege | Belgium | ||
| 19 | Centre Hospitalier Universitaire | Liege | Belgium | ||
| 20 | Ucl de Mont-Godinne | Yvoir | Belgium | ||
| 21 | Centro de Hematologia E Hemoterapia - Unicamp | Campinas | Brazil | ||
| 22 | Fundacao Hospital Amaral Carvalho | Jau | Brazil | ||
| 23 | Hospital Nossa Senhora da Conceicao | Porto Alegre | Brazil | ||
| 24 | Hospital Sao Lucas Puc-Rs | Porto Alegre | Brazil | ||
| 25 | Inca - Instituto Nacional Do Cancêr | Rio de Janeiro | Brazil | ||
| 26 | Centro de Estudos de Hematologia E Oncologia Da Fmabc | Sao Paulo | Brazil | ||
| 27 | Fundacao Pio XII - Hospital de Cancer de Barretos | Sao Paulo | Brazil | ||
| 28 | Hospital Ac Camargo | Sao Paulo | Brazil | ||
| 29 | Hospital Alemao Oswaldo Cruz | Sao Paulo | Brazil | ||
| 30 | Hospital das Clínicas da Faculdade de Medicina da USP | Sao Paulo | Brazil | ||
| 31 | Santa Casa de Misericórida de São Paulo | Sao Paulo | Brazil | ||
| 32 | Cross Cancer Institute | Edmonton | Alberta | Canada | |
| 33 | University Health Network, Princess Margaret Hospital | Toronto | Ontario | Canada | |
| 34 | Hospital Clinico Universidad Catolica de Chile | Santiago | Chile | ||
| 35 | Hospital Del Salvador | Santiago | Chile | ||
| 36 | Instituto Nacional Del Cancer | Santiago | Chile | ||
| 37 | Sun Yat-sen University Cancer Center | Guangzhou | Guangdong | China | |
| 38 | West China Hospital, Sichuan University | Chengdu | Sichuan | China | |
| 39 | Zhejiang University First Hospital | Hangzhou | Zhejiang | China | |
| 40 | Beijing Cancer Hospital | Beijing | China | ||
| 41 | Cancer Institute & Cancer Hospital, CAMS&PUMC | Beijing | China | ||
| 42 | Peking University Third Hospital | Beijing | China | ||
| 43 | Cancer hospital, Fudan University | Shanghai | China | ||
| 44 | Ruijin Hospital | Shanghai | China | ||
| 45 | Tianjin Medical University Cancer Hospital and Institute | Tianjin | China | ||
| 46 | Clinica Reina Sofia | Bogota | Colombia | ||
| 47 | Hospital Pablo Tobon Uribe | Medellin | Colombia | ||
| 48 | Hospital Universitario San Vicente de Paul | Medellin | Colombia | ||
| 49 | Interni hematoonkoligicka klinika | Brno | Czechia | ||
| 50 | Interni klinika - Oddeleni klin. hematologie Fakultni nemocnice Hradec Kralove | Hradec Kralove | Czechia | ||
| 51 | Oddeleni klinicke hematologie, Fakultni nemocnice Kralovske Vinohrady | Praha | Czechia | ||
| 52 | Vivantes Klinikum Neukölln Klinik für Innere Medizin Hämatologie und Onkologie | Berlin | Germany | ||
| 53 | Vivantes Klinikum Spandau Klinik für Innere Medizin - Hämatologie, Onkologie und Gastroenterologie | Berlin | Germany | ||
| 54 | Städt. Kliniken Frankfurt-Hoechst Med. Klinik II - Hämatologie und Onkologie | Frankfurt | Germany | ||
| 55 | Tumorklinik SANAFONTIS Alpine GmbH | Freiburg | Germany | ||
| 56 | Wilhelm-Anton-Hospital Goch gGmbH Klinik für Hämatologie und internistische Onkologie | Goch | Germany | ||
| 57 | Klinikum Lippe-Lemgo Med. Klinik II - Hämatologie und Onkologie | Lemgo | Germany | ||
| 58 | Johannes-Gutenberg-Universität Mainz III. Med. Klinik | Mainz | Germany | ||
| 59 | Mutterhaus der Borromäerinnen Med. Klinik I | Trier | Germany | ||
| 60 | Schwarzwald-Baar-Kliniken Innere Med. II | Villingen | Germany | ||
| 61 | Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum, III. sz. Belgyogyaszati Klinika | Debrecen | Hungary | ||
| 62 | Petz Aladár Kórház, II. Belgyógyászat | Győr | Hungary | ||
| 63 | Kaposi Mor Megyei Korhaz, Belgyogyaszat | Kaposvar | Hungary | ||
| 64 | Apollo Hospital and Research Foundation, Apollo Hospitals | Hyderabad 500033 | Andhra Pradesh | India | |
| 65 | Sir Ganga Ram Hospital | New Delhi- 110060 | Delhi | India | |
| 66 | Kidwai Memorial Institute of Oncology | Bangalore 560 029 | Karnataka | India | |
| 67 | Regional Cancer Centre, Medical Oncology | Thiruvananthapuram | Kerala-695011 | India | |
| 68 | Jehangir Hospital | Pune-411002 | Maharashtra | India | |
| 69 | Apollo Speciality Hospital, Chennai | Chennai-600035 | Tamil Nadu | India | |
| 70 | Netaji Subash Chanda Bose Cancer Research Institute | Kolkata- 700016 | West Bengal | India | |
| 71 | Rambam Medical Center-Hematology department | Haifa | Israel | ||
| 72 | Hadassah Medical Center - Hematology department | Jerusalem | Israel | ||
| 73 | Rabin Medical Center, Beilinson Campus | Petach Tiqva | Israel | ||
| 74 | Sheba Medical Center | Ramat-Gan | Israel | ||
| 75 | Kaplan Medical Center - Hematology Institute | Rechovot | Israel | ||
| 76 | Azienda Ospedaliera Universitaria di Bologna Policlinico S.Orsola-Malpighi Dipartimento di Ematologia e Scienze Oncologiche "L. e A. Seragnoli" | Bologna | Italy | ||
| 77 | Spedali Civili di Brescia | Brescia | Italy | ||
| 78 | Dipartimento di Oncologia ed Ematologia Università di Modena e Reggio Emilia | Modena | Italy | ||
| 79 | AZIENDA OSPEDALIERA UNIVERSITARIA POLICLINICO TOR VERGATA DIPARTIMENTO DI MEDICINA U.O.C. Ematologia | Roma | Italy | ||
| 80 | Azienda Ospedaliera San Giovanni Battista "Molinette" Struttura Complessa Ematologia 2 | Torino | Italy | ||
| 81 | University Malaya Medical Centre | Kuala Lumpur | Malaysia | ||
| 82 | Gleneagles Medical Centre | Pulau Pinang | Malaysia | ||
| 83 | Hopital Du 20 Aout 1953 | Casablanca | Morocco | ||
| 84 | Centre D'oncologie Al Azhar | Rabat | Morocco | ||
| 85 | Institut National D'oncologie | Rabat | Morocco | ||
| 86 | National Kidney and Transplant Institute | Quezon City | Philippines | ||
| 87 | St Lukes Medical Center | Quezon City | Philippines | ||
| 88 | Szpital Morski im. PCK w Gdyni Gdynskie Centrum Onkologii Oddzial Chemioterapii | Gdynia | Poland | ||
| 89 | Klinika Hematologii Uniwersytetu Medycznego w Lodzi | Lodz | Poland | ||
| 90 | "Katedra i Klinika Hematologii i Chorob Rozrostowych Ukladu Krwiotworczego | Poznan | Poland | ||
| 91 | Klinika Hematologii Nowotworow Krwi i Transplantacji Szpiku Akademii Medycznej we Wroclawiu | Wroclaw | Poland | ||
| 92 | Hospital Sao Marcos | Braga | Portugal | ||
| 93 | Hospitais da Universidade de Coimbra | Coimbra | Portugal | ||
| 94 | Hospital de Santa Maria | Lisboa | Portugal | ||
| 95 | Instituto Portugues de Oncologia | Porto | Portugal | ||
| 96 | Spitalul Judetean de Urgenta "Dr. Constantin Opris", Hematologie | Baia Mare | Romania | ||
| 97 | Institutul Clinic Fundeni, Hematologie | Bucuresti | Romania | ||
| 98 | Spitalul Clinic Coltea, Clinica Hematologie | Bucuresti | Romania | ||
| 99 | Spitalul Clinic Universitar de Urgenta Bucuresti, Hematologie | Bucuresti | Romania | ||
| 100 | Spitalul Clinic Judetean de Urgenta "Sf. Spiridon" Iasi, Oncologie Medicala | Iasi | Romania | ||
| 101 | Arkhangelsk Regional Clinical Hospital | Arkhangelsk | Russian Federation | ||
| 102 | Belgorod Regional Oncology Center | Belgorod | Russian Federation | ||
| 103 | Chelyabinsk Regional Oncology Center | Chelyabinsk | Russian Federation | ||
| 104 | Sverdlovsk Regional Oncology Dispensary | Ekaterinburg | Russian Federation | ||
| 105 | 1st Republican Clinical Hospital of Udmurtia | Izhevsk | Russian Federation | ||
| 106 | Cancer Research Center RAMS - N.N. Blokhin - Academy of Medical Science | Moscow | Russian Federation | ||
| 107 | Hematology Scientific Center | Moscow | Russian Federation | ||
| 108 | Moscow Regional Clinical Research Institute | Moscow | Russian Federation | ||
| 109 | S.P. Botkin Moscow City Clinical Hospital | Moscow | Russian Federation | ||
| 110 | Nizhniy Novgorod Region Clinical Hospital | Nizhniy Novgorod | Russian Federation | ||
| 111 | Medical Scientific Radiology - Center | Obninsk | Russian Federation | ||
| 112 | Omsk Regional Oncology Dispensary | Omsk | Russian Federation | ||
| 113 | Medical Sanitary Unit # 1 | Perm | Russian Federation | ||
| 114 | Republikan Hospital named after V.A/ Baranov | Petrozavodsk | Russian Federation | ||
| 115 | Rostov Research Institute of Oncology | Rostov-on-Don | Russian Federation | ||
| 116 | City Clinical Oncology Dispensary | St Petersburg | Russian Federation | ||
| 117 | Central Res. Inst. of Roentgen-Radiology | St-Petersburg | Russian Federation | ||
| 118 | Pavlov State Medical Univercity | St-Petersburg | Russian Federation | ||
| 119 | Leningrad Region Clinical Hospital | St. Petersburg | Russian Federation | ||
| 120 | St.-Petersburg Clinical Research Institute of Hematology and Transfusiology | St. Petersburg | Russian Federation | ||
| 121 | National Cancer Centre | Singapore | Singapore | ||
| 122 | Singapore General Hospital - Hematology | Singapore | Singapore | ||
| 123 | Chris Hani Baragwanath Hospital | Johannesburg | Gauteng | South Africa | |
| 124 | Medical Oncology Center of Rosebank | Johannesburg | Gauteng | South Africa | |
| 125 | University of the Witwatersrand Oncology | Johannesburg | Gauteng | South Africa | |
| 126 | Pretoria Academic Hospital-Dr. Savage Road, 3rd Floor Radiotherapy Building, Prinshof | Pretoria | Gauteng | South Africa | |
| 127 | Dr AI Pirjol & Dr WM Szpak Inc. | Durban | Kwazulu Natal | South Africa | |
| 128 | Hospital Universitario Germans Trias i Pujol | Badalona | Barcelona | Spain | |
| 129 | Hospital Clinic I Provincial de Barcelona | Barcelona | Spain | ||
| 130 | Hospital de la Princesa | Madrid | Spain | ||
| 131 | Hospital Universitario 12 de Octubre | Madrid | Spain | ||
| 132 | Hospital Clinico Universitario Salamanca | Salamanca | Spain | ||
| 133 | Chang Gung Memorial Hospital, Linkou | Tao-Yuan | Taiwan | ||
| 134 | King Chulalongkorn Memorial Hospital | Bangkok | Thailand | ||
| 135 | Ramathibodi Hospital | Bangkok | Thailand | ||
| 136 | Siriraj Hospital-Hematology Unit | Bangkok | Thailand | ||
| 137 | Maharaj Nakorn Chiang Mai hospital - Faculty of Medicine | Chiang Mai | Thailand | ||
| 138 | Hôpital Farhat Hached | Sousse | Tunisia | ||
| 139 | Centre National de Greffe de Moelle osseuse | Tunis | Tunisia | ||
| 140 | Hôpital Aziza Othmana | Tunis | Tunisia | ||
| 141 | Institut Salah Azaiz | Tunis | Tunisia | ||
| 142 | Hacettepe University Medical Faculty | Ankara | Turkey | ||
| 143 | Dokuz Eylul University Med. Fac. | Izmir | Turkey | ||
| 144 | Cherkassy Regional Oncology Center, Dept. of Hematology | Cherkassy | Ukraine | ||
| 145 | Dnepropetrovsk City Clinical Hospital #4, Regional Hematology Center | Dnepropetrovsk | Ukraine | ||
| 146 | Institute of Urgent and Recovery Surgery named after V.K.Gusaka of AMS of Ukraine, Haematology Dept. | Donetsk | Ukraine | ||
| 147 | Khmelnitskiy Regional Hospital, Hematology Department | Khmelnitsky | Ukraine | ||
| 148 | National Cancer Institute, Department of chemotherapy of hemoblastosis | Kiev | Ukraine | ||
| 149 | Institute of Blood Pathology and Transfusion Medicine, Lviv Clinical Hospital #5, Hematology Dept. | Lviv | Ukraine | ||
| 150 | Crimean Republic Clinical Oncology Dispensary, Haematology Department | Simferopol | Ukraine |
Sponsors and Collaborators
- Millennium Pharmaceuticals, Inc.
- Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
- Study Director: Medical Director Clinical Science, Takeda
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00722137
Other Study ID Numbers:
- 26866138-LYM-3002
- 26866138-LYM-3002CTIL
- 2007-005669-37
- 0970313683
- U1111-1195-3827
First Posted:
Jul 25, 2008
Last Update Posted:
Jul 12, 2018
Last Verified:
Jun 1, 2018
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | A total of 487 participants were randomized from 128 centers in 28 countries from 22 May 2008 to 17 June 2017; 244 to the R-CHOP treatment group and 243 to the VcR-CAP treatment group. Of the 487 randomized participants, 242 in the R-CHOP group and 240 in the VcR-CAP group received at least 1 dose of study drug. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | R-CHOP | VcR-CAP |
|---|---|---|
| Arm/Group Description | Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, Vincristine 1.4 mg/m^2 and Prednisone 100 mg/m^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. | Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, VELCADE 1.3 mg/m^2, and Prednisone 100 mg/m^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles. |
| Period Title: Overall Study | ||
| STARTED | 244 | 243 |
| COMPLETED | 199 | 195 |
| NOT COMPLETED | 45 | 48 |
Baseline Characteristics
| Arm/Group Title | R-CHOP | VcR-CAP | Total |
|---|---|---|---|
| Arm/Group Description | Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, Vincristine 1.4 mg/m^2 and Prednisone 100 mg/m^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. | Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, VELCADE 1.3 mg/m^2, and Prednisone 100 mg/m^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles. | Total of all reporting groups |
| Overall Participants | 244 | 243 | 487 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
64.4
(8.78)
|
64.2
(9.68)
|
64.3
(9.23)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
62
25.4%
|
65
26.7%
|
127
26.1%
|
| Male |
182
74.6%
|
178
73.3%
|
360
73.9%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
68
27.9%
|
88
36.2%
|
156
32%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
3
1.2%
|
3
0.6%
|
| White |
172
70.5%
|
151
62.1%
|
323
66.3%
|
| More than one race |
4
1.6%
|
1
0.4%
|
5
1%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (Count of Participants) | |||
| Belgium |
10
4.1%
|
16
6.6%
|
26
5.3%
|
| Poland |
9
3.7%
|
10
4.1%
|
19
3.9%
|
| Czech Republic |
5
2%
|
9
3.7%
|
14
2.9%
|
| Spain |
8
3.3%
|
6
2.5%
|
14
2.9%
|
| Hungary |
5
2%
|
8
3.3%
|
13
2.7%
|
| Romania |
9
3.7%
|
4
1.6%
|
13
2.7%
|
| Austria |
6
2.5%
|
4
1.6%
|
10
2.1%
|
| Italy |
6
2.5%
|
3
1.2%
|
9
1.8%
|
| Germany |
7
2.9%
|
1
0.4%
|
8
1.6%
|
| Portugal |
3
1.2%
|
4
1.6%
|
7
1.4%
|
| France |
1
0.4%
|
2
0.8%
|
3
0.6%
|
| Canada |
6
2.5%
|
1
0.4%
|
7
1.4%
|
| United States |
2
0.8%
|
5
2.1%
|
7
1.4%
|
| Russia |
57
23.4%
|
42
17.3%
|
99
20.3%
|
| China |
34
13.9%
|
61
25.1%
|
95
19.5%
|
| Ukraine |
18
7.4%
|
16
6.6%
|
34
7%
|
| Brazil |
9
3.7%
|
13
5.3%
|
22
4.5%
|
| Thailand |
9
3.7%
|
10
4.1%
|
19
3.9%
|
| Japan |
11
4.5%
|
7
2.9%
|
18
3.7%
|
| India |
9
3.7%
|
3
1.2%
|
12
2.5%
|
| Israel |
5
2%
|
2
0.8%
|
7
1.4%
|
| Tunisia |
3
1.2%
|
3
1.2%
|
6
1.2%
|
| Turkey |
5
2%
|
1
0.4%
|
6
1.2%
|
| Colombia |
2
0.8%
|
3
1.2%
|
5
1%
|
| Korea, Republic Of |
2
0.8%
|
3
1.2%
|
5
1%
|
| Chile |
1
0.4%
|
2
0.8%
|
3
0.6%
|
| Singapore |
1
0.4%
|
2
0.8%
|
3
0.6%
|
| Taiwan, Province Of China |
1
0.4%
|
2
0.8%
|
3
0.6%
|
Outcome Measures
| Title | Progression Free Survival (PFS) |
|---|---|
| Description | PFS was defined as the interval between the date of randomization and the date of progressive disease (PD) or death, whichever occurred first. PD was based on the assessment of an Independent Review Committee. |
| Time Frame | Median duration of follow-up of 40 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The population consisted of all randomized participants. |
| Arm/Group Title | R-CHOP | VcR-CAP |
|---|---|---|
| Arm/Group Description | Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, Vincristine 1.4 mg/m^2 and Prednisone 100 mg/m^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. | Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, VELCADE 1.3 mg/m^2, and Prednisone 100 mg/m^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles. |
| Measure Participants | 244 | 243 |
| Median (95% Confidence Interval) [Days] |
437.0
|
751.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | R-CHOP, VcR-CAP |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Log Rank | |
| Comments | Based on Log rank test stratified with International Prognostic Index (IPI) risk and stage of disease. | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.63 | |
| Confidence Interval |
(2-Sided) 95% 0.50 to 0.79 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Hazards ratio estimate is based on a Cox´s model stratified by IPI risk and stage of disease. A hazard ratio < 1 indicates an advantage for VcR-CAP. | |
| Title | Time to Progression (TTP) |
|---|---|
| Description | Time to progression was defined as the duration from the date of randomization until the date of first documented evidence of progressive disease (PD) or date of relapse for subjects who experienced complete response (CR) or complete response, unconfirmed (CRu). PD and response were based on the assessment of an Independent Review Committee. |
| Time Frame | Median duration of follow-up of 40 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The population consisted of all randomized participants. |
| Arm/Group Title | R-CHOP | VcR-CAP |
|---|---|---|
| Arm/Group Description | Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, Vincristine 1.4 mg/m^2 and Prednisone 100 mg/m^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. | Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, VELCADE 1.3 mg/m^2, and Prednisone 100 mg/m^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles. |
| Measure Participants | 244 | 243 |
| Median (95% Confidence Interval) [Days] |
490.0
|
929.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | R-CHOP, VcR-CAP |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Log Rank | |
| Comments | Based on Log rank test stratified with IPI risk and stage of disease. | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.58 | |
| Confidence Interval |
(2-Sided) 95% 0.45 to 0.74 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Hazards ratio estimate is based on a Cox´s model stratified by IPI risk and stage of disease. A hazard ratio < 1 indicates an advantage for VcR-CAP. | |
| Title | Duration of Response |
|---|---|
| Description | The duration of treatment response was defined as the time from the date of the first response to the date of PD or death due to PD for those participants with a best response of CR, CRu, or PR as determined by the Independent Review Committee. The duration of response for complete responders was defined as the time from the date of the first response to the date of PD or death due to PD for those participants with a best response of CR or CRu verified by bone marrow and lactate dehydrogenase (LDH). |
| Time Frame | Median duration of follow-up of 40 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The response-evaluable population was defined as all participants who received at least 1 dose of study drug, had >= 1 measurable tumor mass (>1.5 cm in the longest dimension and >1.0 cm in the short axis) at baseline and had at least 1 post-baseline tumor assessment by Independent Review Committee, before any subsequent anti-lymphoma treatment. |
| Arm/Group Title | R-CHOP | VcR-CAP |
|---|---|---|
| Arm/Group Description | Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, Vincristine 1.4 mg/m^2 and Prednisone 100 mg/m^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. | Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, VELCADE 1.3 mg/m^2, and Prednisone 100 mg/m^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles. |
| Measure Participants | 228 | 229 |
| Duration of response |
459.0
|
1110.0
|
| Duration for Complete responders |
563.0
|
1282.0
|
| Title | Time to Next Anti-lymphoma Treatment (TTNT) |
|---|---|
| Description | The time to next anti-lymphomatreatment was measured from the date of initiation of study treatment as per protocol to the start date of new anti-lymphoma treatment. Death due to disease progression prior to subsequent therapy was considered as an event. Otherwise, time to next anti lymphoma treatment was censored at the date of death or the last date known to be alive. |
| Time Frame | : Median duration of follow-up of 40 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The population consisted of all randomized participants. |
| Arm/Group Title | R-CHOP | VcR-CAP |
|---|---|---|
| Arm/Group Description | Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, Vincristine 1.4 mg/m^2 and Prednisone 100 mg/m^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. | Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, VELCADE 1.3 mg/m^2, and Prednisone 100 mg/m^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles. |
| Measure Participants | 244 | 243 |
| Median (95% Confidence Interval) [Days] |
756.0
|
1353.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | R-CHOP, VcR-CAP |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Log Rank | |
| Comments | Based on Log rank test stratified with IPI risk and stage of disease. | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.50 | |
| Confidence Interval |
(2-Sided) 95% 0.38 to 0.65 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Hazards ratio estimate is based on a Cox´s model stratified by IPI risk and stage of disease. A hazard ratio < 1 indicates an advantage for VcR-CAP. | |
| Title | Treatment-free Interval (TFI) |
|---|---|
| Description | The TFI was defined as the duration from the date of last dose plus 1 day to the start date of the new treatment. Death due to disease progression prior to subsequent therapy was considered as an event. Otherwise, treatment-free interval was censored at the date of death or the last date known to be alive. |
| Time Frame | Median duration of follow-up of 40 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of study medication. |
| Arm/Group Title | R-CHOP | VcR-CAP |
|---|---|---|
| Arm/Group Description | Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, Vincristine 1.4 mg/m^2 and Prednisone 100 mg/m^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. | Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, VELCADE 1.3 mg/m^2, and Prednisone 100 mg/m^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles. |
| Measure Participants | 242 | 240 |
| Median (95% Confidence Interval) [Days] |
624.0
|
1236.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | R-CHOP, VcR-CAP |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.001 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.50 | |
| Confidence Interval |
(2-Sided) 95% 0.38 to 0.65 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Overall Response Rate (ORR) |
|---|---|
| Description | ORR was defined as complete response (CR) + complete response, unconfirmed (CRu) + partial response (PR) as determined by the Independent Review Committee. Response assessment was carried out every 6 weeks for 18 weeks; thereafter, every 8 weeks until PD/initiation of alternate therapy/withdrawal from study/death. |
| Time Frame | Median duration of follow-up of 40 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The response-evaluable population was defined as all participants who received >= 1 dose of study drug, had at least 1 measurable tumor mass (>1.5 cm in the longest dimension and >1.0 cm in the short axis) at baseline and had at least 1 post-baseline tumor assessment by Independent Review Committee, before any subsequent anti-lymphoma treatment. |
| Arm/Group Title | R-CHOP | VcR-CAP |
|---|---|---|
| Arm/Group Description | Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, Vincristine 1.4 mg/m^2 and Prednisone 100 mg/m^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. | Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, VELCADE 1.3 mg/m^2, and Prednisone 100 mg/m^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles. |
| Measure Participants | 228 | 229 |
| Number [Participants] |
204
83.6%
|
211
86.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | R-CHOP, VcR-CAP |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.275 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel Chi-Square | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.428 | |
| Confidence Interval |
(2-Sided) 95% 0.749 to 2.722 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Mantel-Haenszel estimate of the common odds ratio for stratified tables is used, with IPI risk and Stage of Disease as stratification factors. An odds ratio (OR) > 1 indicates an advantage for VcR-CAP. | |
| Title | Overall Complete Response (CR + CRu) |
|---|---|
| Description | Overall complete response was defined as the number of participants with complete response (CR) and those with unconfirmed complete response (CRu). Response assessment was carried out every 6 weeks for 18 weeks; thereafter, every 8 weeks until PD/initiation of alternate therapy/withdrawal from study/death. |
| Time Frame | Median duration of follow-up of 40 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The response-evaluable population was defined as all participants who received >= 1 dose of study drug, had at least 1 measurable tumor mass (>1.5 cm in the longest dimension and >1.0 cm in the short axis) at baseline and had at least 1 post-baseline tumor assessment by Independent Review Committee, before any subsequent anti-lymphoma treatment. |
| Arm/Group Title | R-CHOP | VcR-CAP |
|---|---|---|
| Arm/Group Description | Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, Vincristine 1.4 mg/m^2 and Prednisone 100 mg/m^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. | Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, VELCADE 1.3 mg/m^2, and Prednisone 100 mg/m^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles. |
| Measure Participants | 228 | 229 |
| Overall complete response |
95
38.9%
|
122
50.2%
|
| CR |
79
32.4%
|
106
43.6%
|
| CRu |
16
6.6%
|
16
6.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | R-CHOP, VcR-CAP |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.007 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel Chi-Square | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.688 | |
| Confidence Interval |
(2-Sided) 95% 1.148 to 2.481 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Mantel-Haenszel estimate of the common odds ratio for stratified tables is used, with IPI risk and Stage of Disease as stratification factors. An odds ratio (OR) > 1 indicates an advantage for VcR-CAP. | |
| Title | Overall Survival (OS) |
|---|---|
| Description | OS was measured from the date of randomization to the date of the participant's death. If the participant was alive or the vital status was unknown, OS was censored at the date that the subject was last known to be alive. |
| Time Frame | Median duration of follow-up of 40 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The population consisted of all randomized participants. |
| Arm/Group Title | R-CHOP | VcR-CAP |
|---|---|---|
| Arm/Group Description | Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, Vincristine 1.4 mg/m^2 and Prednisone 100 mg/m^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. | Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, VELCADE 1.3 mg/m^2, and Prednisone 100 mg/m^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles. |
| Measure Participants | 244 | 243 |
| Median (95% Confidence Interval) [Days] |
1714.0
|
NA
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | R-CHOP, VcR-CAP |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.173 |
| Comments | ||
| Method | Log Rank | |
| Comments | Based on Log rank test stratified with IPI risk and stage of disease. | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.80 | |
| Confidence Interval |
(2-Sided) 95% 0.59 to 1.10 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Hazards ratio estimate is based on a Cox´s model stratified by IPI risk and stage of disease. A hazard ratio < 1 indicates an advantage for VcR-CAP. | |
| Title | 18-Month Survival |
|---|---|
| Description | 18-month survival was defined as the estimated probability of survival at 18 months (Kaplan-Meier estimate). |
| Time Frame | Up to month 18 from the time of randomization |
Outcome Measure Data
| Analysis Population Description |
|---|
| The population consisted of all randomized participants. |
| Arm/Group Title | R-CHOP | VcR-CAP |
|---|---|---|
| Arm/Group Description | Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, Vincristine 1.4 mg/m^2 and Prednisone 100 mg/m^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. | Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, VELCADE 1.3 mg/m^2, and Prednisone 100 mg/m^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles. |
| Measure Participants | 244 | 243 |
| Mean (95% Confidence Interval) [Percentage of Participants] |
83.8
34.3%
|
84.9
34.9%
|
| Title | Overall Survival (OS) in Long Term Follow-up Period |
|---|---|
| Description | OS was measured from the date of randomization to the date of the participant's death. If the participant was alive or the vital status was unknown, OS was censored at the date that the subject was last known to be alive. |
| Time Frame | Up to 107.4 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The population consisted of all randomized participants. |
| Arm/Group Title | R-CHOP | VcR-CAP |
|---|---|---|
| Arm/Group Description | Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, Vincristine 1.4 mg/m^2 and Prednisone 100 mg/m^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. | Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, VELCADE 1.3 mg/m^2, and Prednisone 100 mg/m^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles. |
| Measure Participants | 244 | 243 |
| Median (95% Confidence Interval) [Days] |
1695.0
|
2760.0
|
| Title | Number of Participants Experiencing an Adverse Event (AE) |
|---|---|
| Description | An AE was defined as any untoward medical occurrence associated with the use of a drug, whether or not considered drug related. AEs were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 8 cycles (24 weeks) and AEs were collected for up to 30 days following the last dose of study drug. |
| Time Frame | Up to 107.4 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population was defined as all randomized participants who received at least 1 dose of study medication. |
| Arm/Group Title | R-CHOP | VcR-CAP |
|---|---|---|
| Arm/Group Description | Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, Vincristine 1.4 mg/m^2 and Prednisone 100 mg/m^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. | Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, VELCADE 1.3 mg/m^2, and Prednisone 100 mg/m^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles. |
| Measure Participants | 242 | 240 |
| Number [Participants] |
239
98%
|
240
98.8%
|
Adverse Events
| Time Frame | Up to 107.4 months | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | The safety population was defined as all randomized participants who received at least 1 dose of study medication. | |||
| Arm/Group Title | R-CHOP | VcR-CAP | ||
| Arm/Group Description | Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, Vincristine 1.4 mg/m^2 and Prednisone 100 mg/m^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. | Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, VELCADE 1.3 mg/m^2, and Prednisone 100 mg/m^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles. | ||
All Cause Mortality |
||||
| R-CHOP | VcR-CAP | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| R-CHOP | VcR-CAP | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 72/242 (29.8%) | 91/240 (37.9%) | ||
| Blood and lymphatic system disorders | ||||
| Febrile neutropenia | 20/242 (8.3%) | 26/240 (10.8%) | ||
| Neutropenia | 13/242 (5.4%) | 12/240 (5%) | ||
| Thrombocytopenia | 1/242 (0.4%) | 8/240 (3.3%) | ||
| Leukopenia | 3/242 (1.2%) | 6/240 (2.5%) | ||
| Anaemia | 5/242 (2.1%) | 4/240 (1.7%) | ||
| Lymphopenia | 0/242 (0%) | 1/240 (0.4%) | ||
| Bone marrow failure | 0/242 (0%) | 1/240 (0.4%) | ||
| Cardiac disorders | ||||
| Left ventricular dysfunction | 0/242 (0%) | 3/240 (1.3%) | ||
| Cardiac failure | 0/242 (0%) | 2/240 (0.8%) | ||
| Atrial fibrillation | 2/242 (0.8%) | 1/240 (0.4%) | ||
| Cardiac failure congestive | 0/242 (0%) | 1/240 (0.4%) | ||
| Cardiogenic shock | 0/242 (0%) | 1/240 (0.4%) | ||
| Myocardial ischaemia | 1/242 (0.4%) | 1/240 (0.4%) | ||
| Sinus tachycardia | 0/242 (0%) | 1/240 (0.4%) | ||
| Supraventricular extrasystoles | 0/242 (0%) | 1/240 (0.4%) | ||
| Acute left ventricular failure | 1/242 (0.4%) | 0/240 (0%) | ||
| Acute myocardial infarction | 1/242 (0.4%) | 0/240 (0%) | ||
| Cardiac arrest | 1/242 (0.4%) | 0/240 (0%) | ||
| Cardiac failure acute | 1/242 (0.4%) | 0/240 (0%) | ||
| Cardio-respiratory arrest | 2/242 (0.8%) | 0/240 (0%) | ||
| Cardiomyopathy | 1/242 (0.4%) | 0/240 (0%) | ||
| Cardiopulmonary failure | 1/242 (0.4%) | 0/240 (0%) | ||
| Left ventricular failure | 1/242 (0.4%) | 0/240 (0%) | ||
| Myocardial infarction | 2/242 (0.8%) | 0/240 (0%) | ||
| Tachycardia | 2/242 (0.8%) | 0/240 (0%) | ||
| Gastrointestinal disorders | ||||
| Diarrhoea | 3/242 (1.2%) | 4/240 (1.7%) | ||
| Vomiting | 1/242 (0.4%) | 2/240 (0.8%) | ||
| Abdominal adhesions | 0/242 (0%) | 1/240 (0.4%) | ||
| Colitis | 1/242 (0.4%) | 1/240 (0.4%) | ||
| Gastritis | 0/242 (0%) | 1/240 (0.4%) | ||
| Gastrointestinal haemorrhage | 0/242 (0%) | 1/240 (0.4%) | ||
| Ileus paralytic | 0/242 (0%) | 1/240 (0.4%) | ||
| Melaena | 1/242 (0.4%) | 1/240 (0.4%) | ||
| Mouth ulceration | 0/242 (0%) | 1/240 (0.4%) | ||
| Oesophagitis | 0/242 (0%) | 1/240 (0.4%) | ||
| Stomatitis | 2/242 (0.8%) | 1/240 (0.4%) | ||
| Anal fissure | 1/242 (0.4%) | 0/240 (0%) | ||
| Constipation | 1/242 (0.4%) | 0/240 (0%) | ||
| Haematemesis | 1/242 (0.4%) | 0/240 (0%) | ||
| Pancreatitis | 1/242 (0.4%) | 0/240 (0%) | ||
| Periproctitis | 1/242 (0.4%) | 0/240 (0%) | ||
| Small intestinal obstruction | 1/242 (0.4%) | 0/240 (0%) | ||
| General disorders | ||||
| Pyrexia | 4/242 (1.7%) | 10/240 (4.2%) | ||
| Acute phase reaction | 0/242 (0%) | 1/240 (0.4%) | ||
| Asthenia | 0/242 (0%) | 1/240 (0.4%) | ||
| Chills | 1/242 (0.4%) | 1/240 (0.4%) | ||
| Death | 0/242 (0%) | 1/240 (0.4%) | ||
| Cardiac death | 1/242 (0.4%) | 0/240 (0%) | ||
| Chest pain | 1/242 (0.4%) | 0/240 (0%) | ||
| Fatigue | 3/242 (1.2%) | 0/240 (0%) | ||
| Oedema peripheral | 1/242 (0.4%) | 0/240 (0%) | ||
| Hepatobiliary disorders | ||||
| Hepatic failure | 0/242 (0%) | 1/240 (0.4%) | ||
| Bile duct stone | 1/242 (0.4%) | 0/240 (0%) | ||
| Hepatic function abnormal | 1/242 (0.4%) | 0/240 (0%) | ||
| Infections and infestations | ||||
| Pneumonia | 7/242 (2.9%) | 19/240 (7.9%) | ||
| Sepsis | 1/242 (0.4%) | 4/240 (1.7%) | ||
| Bronchitis | 2/242 (0.8%) | 2/240 (0.8%) | ||
| Lobar pneumonia | 1/242 (0.4%) | 2/240 (0.8%) | ||
| Lung infection | 1/242 (0.4%) | 2/240 (0.8%) | ||
| Pneumonia streptococcal | 0/242 (0%) | 2/240 (0.8%) | ||
| Septic shock | 1/242 (0.4%) | 2/240 (0.8%) | ||
| Abscess neck | 0/242 (0%) | 1/240 (0.4%) | ||
| Bronchopneumonia | 1/242 (0.4%) | 1/240 (0.4%) | ||
| Candidiasis | 0/242 (0%) | 1/240 (0.4%) | ||
| Cellulitis | 0/242 (0%) | 1/240 (0.4%) | ||
| Erysipelas | 0/242 (0%) | 1/240 (0.4%) | ||
| Hepatitis B | 2/242 (0.8%) | 1/240 (0.4%) | ||
| Herpes zoster | 1/242 (0.4%) | 1/240 (0.4%) | ||
| Klebsiella sepsis | 0/242 (0%) | 1/240 (0.4%) | ||
| Nosocomial infection | 0/242 (0%) | 1/240 (0.4%) | ||
| Parotitis | 0/242 (0%) | 1/240 (0.4%) | ||
| Pneumonia bacterial | 0/242 (0%) | 1/240 (0.4%) | ||
| Pneumonia cytomegaloviral | 0/242 (0%) | 1/240 (0.4%) | ||
| Postoperative abscess | 0/242 (0%) | 1/240 (0.4%) | ||
| Pulmonary mycosis | 0/242 (0%) | 1/240 (0.4%) | ||
| Respiratory tract infection | 1/242 (0.4%) | 1/240 (0.4%) | ||
| Salmonellosis | 0/242 (0%) | 1/240 (0.4%) | ||
| Upper respiratory tract infection | 1/242 (0.4%) | 1/240 (0.4%) | ||
| Urinary tract infection | 0/242 (0%) | 1/240 (0.4%) | ||
| Anal abscess | 1/242 (0.4%) | 0/240 (0%) | ||
| Bacterial sepsis | 1/242 (0.4%) | 0/240 (0%) | ||
| Clostridium difficile infection | 1/242 (0.4%) | 0/240 (0%) | ||
| Endocarditis bacterial | 1/242 (0.4%) | 0/240 (0%) | ||
| Escherichia urinary tract infection | 1/242 (0.4%) | 0/240 (0%) | ||
| Gastroenteritis | 2/242 (0.8%) | 0/240 (0%) | ||
| Oral fungal infection | 1/242 (0.4%) | 0/240 (0%) | ||
| Oral herpes | 1/242 (0.4%) | 0/240 (0%) | ||
| Oropharyngeal candidiasis | 1/242 (0.4%) | 0/240 (0%) | ||
| Paronychia | 1/242 (0.4%) | 0/240 (0%) | ||
| Peritonsillar abscess | 1/242 (0.4%) | 0/240 (0%) | ||
| Pulmonary tuberculosis | 1/242 (0.4%) | 0/240 (0%) | ||
| Rectal abscess | 1/242 (0.4%) | 0/240 (0%) | ||
| Tracheobronchitis | 1/242 (0.4%) | 0/240 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Femur fracture | 1/242 (0.4%) | 1/240 (0.4%) | ||
| Compression fracture | 1/242 (0.4%) | 0/240 (0%) | ||
| Traumatic lung injury | 1/242 (0.4%) | 0/240 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Hypokalaemia | 0/242 (0%) | 2/240 (0.8%) | ||
| Decreased appetite | 0/242 (0%) | 1/240 (0.4%) | ||
| Fluid retention | 0/242 (0%) | 1/240 (0.4%) | ||
| Hyponatraemia | 0/242 (0%) | 1/240 (0.4%) | ||
| Tumour lysis syndrome | 2/242 (0.8%) | 1/240 (0.4%) | ||
| Dehydration | 1/242 (0.4%) | 0/240 (0%) | ||
| Diabetes mellitus | 1/242 (0.4%) | 0/240 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Soft tissue necrosis | 1/242 (0.4%) | 0/240 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Malignant melanoma | 1/242 (0.4%) | 0/240 (0%) | ||
| Gastric cancer | 0/242 (0%) | 1/240 (0.4%) | ||
| Nervous system disorders | ||||
| Neuralgia | 0/242 (0%) | 2/240 (0.8%) | ||
| Autonomic neuropathy | 0/242 (0%) | 1/240 (0.4%) | ||
| Cerebral ischaemia | 0/242 (0%) | 1/240 (0.4%) | ||
| Depressed level of consciousness | 0/242 (0%) | 1/240 (0.4%) | ||
| Encephalitis | 0/242 (0%) | 1/240 (0.4%) | ||
| Peripheral sensorimotor neuropathy | 0/242 (0%) | 1/240 (0.4%) | ||
| Peripheral sensory neuropathy | 0/242 (0%) | 1/240 (0.4%) | ||
| Syncope | 0/242 (0%) | 1/240 (0.4%) | ||
| Cerebrovascular accident | 1/242 (0.4%) | 0/240 (0%) | ||
| Convulsion | 1/242 (0.4%) | 0/240 (0%) | ||
| Renal and urinary disorders | ||||
| Renal failure | 1/242 (0.4%) | 0/240 (0%) | ||
| Renal impairment | 1/242 (0.4%) | 0/240 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Pulmonary embolism | 1/242 (0.4%) | 4/240 (1.7%) | ||
| Pleural effusion | 1/242 (0.4%) | 3/240 (1.3%) | ||
| Dyspnoea | 5/242 (2.1%) | 2/240 (0.8%) | ||
| Acute respiratory distress syndrome | 0/242 (0%) | 1/240 (0.4%) | ||
| Aspiration | 0/242 (0%) | 1/240 (0.4%) | ||
| Pneumonia aspiration | 0/242 (0%) | 1/240 (0.4%) | ||
| Pulmonary hypertension | 0/242 (0%) | 1/240 (0.4%) | ||
| Pulmonary oedema | 0/242 (0%) | 1/240 (0.4%) | ||
| Respiratory failure | 0/242 (0%) | 1/240 (0.4%) | ||
| Tonsillar haemorrhage | 0/242 (0%) | 1/240 (0.4%) | ||
| Acute respiratory failure | 1/242 (0.4%) | 0/240 (0%) | ||
| Epistaxis | 1/242 (0.4%) | 0/240 (0%) | ||
| Lung infiltration | 1/242 (0.4%) | 0/240 (0%) | ||
| Respiratory distress | 2/242 (0.8%) | 0/240 (0%) | ||
| Vascular disorders | ||||
| Hypotension | 1/242 (0.4%) | 3/240 (1.3%) | ||
| Orthostatic hypotension | 0/242 (0%) | 2/240 (0.8%) | ||
| Poor venous access | 0/242 (0%) | 2/240 (0.8%) | ||
| Deep vein thrombosis | 3/242 (1.2%) | 1/240 (0.4%) | ||
| Hypertension | 0/242 (0%) | 1/240 (0.4%) | ||
| Venous thrombosis | 0/242 (0%) | 1/240 (0.4%) | ||
Other (Not Including Serious) Adverse Events |
||||
| R-CHOP | VcR-CAP | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 187/242 (77.3%) | 185/240 (77.1%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 33/242 (13.6%) | 59/240 (24.6%) | ||
| Abdominal distension | 5/242 (2.1%) | 22/240 (9.2%) | ||
| Abdominal pain | 9/242 (3.7%) | 18/240 (7.5%) | ||
| Abdominal pain upper | 11/242 (4.5%) | 16/240 (6.7%) | ||
| Dyspepsia | 14/242 (5.8%) | 13/240 (5.4%) | ||
| Investigations | ||||
| Weight decreased | 10/242 (4.1%) | 14/240 (5.8%) | ||
| Metabolism and nutrition disorders | ||||
| Hyperglycaemia | 20/242 (8.3%) | 18/240 (7.5%) | ||
| Hypoalbuminaemia | 11/242 (4.5%) | 14/240 (5.8%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Pain in extremity | 5/242 (2.1%) | 20/240 (8.3%) | ||
| Back pain | 15/242 (6.2%) | 15/240 (6.3%) | ||
| Nervous system disorders | ||||
| Neuropathy peripheral | 19/242 (7.9%) | 19/240 (7.9%) | ||
| Paraesthesia | 12/242 (5%) | 16/240 (6.7%) | ||
| Dizziness | 9/242 (3.7%) | 15/240 (6.3%) | ||
| Hypoaesthesia | 15/242 (6.2%) | 15/240 (6.3%) | ||
| Headache | 11/242 (4.5%) | 13/240 (5.4%) | ||
| Psychiatric disorders | ||||
| Insomnia | 18/242 (7.4%) | 27/240 (11.3%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 20/242 (8.3%) | 49/240 (20.4%) | ||
| Oropharyngeal pain | 10/242 (4.1%) | 14/240 (5.8%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 33/242 (13.6%) | 33/240 (13.8%) | ||
| Rash | 8/242 (3.3%) | 13/240 (5.4%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Results Point of Contact
| Name/Title | Medical Director |
|---|---|
| Organization | Takeda |
| Phone | +1-877-825-3327 |
| trialdisclosures@takeda.com |
Responsible Party:
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00722137
Other Study ID Numbers:
- 26866138-LYM-3002
- 26866138-LYM-3002CTIL
- 2007-005669-37
- 0970313683
- U1111-1195-3827
First Posted:
Jul 25, 2008
Last Update Posted:
Jul 12, 2018
Last Verified:
Jun 1, 2018