Clinical trial NCT00722137: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Mantle Cell Lymphoma
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
First posted: 2008-07-25
Enrollment: 487
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Median duration of follow-up of 40 months
Secondary outcomes:
measure: Time to Progression (TTP)
timeFrame: Median duration of follow-up of 40 months
measure: Duration of Response
timeFrame: Median duration of follow-up of 40 months
measure: Time to Next Anti-lymphoma Treatment (TTNT)
timeFrame: : Median duration of follow-up of 40 months
measure: Treatment-free Interval (TFI)
timeFrame: Median duration of follow-up of 40 months
measure: Overall Response Rate (ORR)
timeFrame: Median duration of follow-up of 40 months
measure: Overall Complete Response (CR + CRu)
timeFrame: Median duration of follow-up of 40 months
measure: Overall Survival (OS)
timeFrame: Median duration of follow-up of 40 months
measure: 18-Month Survival
timeFrame: Up to month 18 from the time of randomization
measure: Overall Survival (OS) in Long Term Follow-up Period
timeFrame: Up to 107.4 months
measure: Number of Participants Experiencing an Adverse Event (AE)
timeFrame: Up to 107.4 months
Other outcomes:
Locations:
city: Hartford
country: United States
facility: St. Francis Hosptial and Medical Center
state: Connecticut
city: Goshen
country: United States
facility: Center for Cancer Care at Goshen Hospital
state: Indiana
city: Baltimore
country: United States
facility: Sinai Hospital
state: Maryland
city: Jefferson City
country: United States
facility: Capitol Comp. Cancer Center
state: Missouri
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Morristown
country: United States
facility: Hematology-Oncology Associates of Northern NJ
state: New Jersey
city: Bismarck
country: United States
facility: Legacy Pharma Research
state: North Dakota
city: Nashville
country: United States
facility: Division of Hematology and Oncology Vanderbilt University
state: Tennessee
city: Abingdon
country: United States
facility: Cancer Outreach Associates, PC
state: Virginia
city: Salzburg
country: Austria
facility: St.Johanns Spital/Landeskrankenhaus Salzburg
city: Wien
country: Austria
facility: Allgemeines Krankenhaus der Stadt Wien
city: Antwerpen
country: Belgium
facility: AZ Stuivenberg Oncologie/ Hematologie
city: Brugge
country: Belgium
facility: AZ St Jan AV
city: Brussels
country: Belgium
facility: UZ Brussel Department Medical Oncology
city: Edegem
country: Belgium
facility: UZA Hematologie, 1e verdiep
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent - UZ GENT, Hematologie, 9K12IE 9de verdiep- polikliniek Hematologie
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg Hematologie
city: Liege
country: Belgium
facility: C.H.R. Citadelle
city: Liege
country: Belgium
facility: Centre Hospitalier Universitaire
city: Yvoir
country: Belgium
facility: Ucl de Mont-Godinne
city: Campinas
country: Brazil
facility: Centro de Hematologia E Hemoterapia - Unicamp
city: Jau
country: Brazil
facility: Fundacao Hospital Amaral Carvalho
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceicao
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas Puc-Rs
city: Rio de Janeiro
country: Brazil
facility: Inca - Instituto Nacional Do Cancêr
city: Sao Paulo
country: Brazil
facility: Centro de Estudos de Hematologia E Oncologia Da Fmabc
city: Sao Paulo
country: Brazil
facility: Fundacao Pio XII - Hospital de Cancer de Barretos
city: Sao Paulo
country: Brazil
facility: Hospital Ac Camargo
city: Sao Paulo
country: Brazil
facility: Hospital Alemao Oswaldo Cruz
city: Sao Paulo
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina da USP
city: Sao Paulo
country: Brazil
facility: Santa Casa de Misericórida de São Paulo
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Toronto
country: Canada
facility: University Health Network, Princess Margaret Hospital
state: Ontario
city: Santiago
country: Chile
facility: Hospital Clinico Universidad Catolica de Chile
city: Santiago
country: Chile
facility: Hospital Del Salvador
city: Santiago
country: Chile
facility: Instituto Nacional Del Cancer
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Hangzhou
country: China
facility: Zhejiang University First Hospital
state: Zhejiang
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: Cancer Institute & Cancer Hospital, CAMS&PUMC
city: Beijing
country: China
facility: Peking University Third Hospital
city: Shanghai
country: China
facility: Cancer hospital, Fudan University
city: Shanghai
country: China
facility: Ruijin Hospital
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Hospital and Institute
city: Bogota
country: Colombia
facility: Clinica Reina Sofia
city: Medellin
country: Colombia
facility: Hospital Pablo Tobon Uribe
city: Medellin
country: Colombia
facility: Hospital Universitario San Vicente de Paul
city: Brno
country: Czechia
facility: Interni hematoonkoligicka klinika
city: Hradec Kralove
country: Czechia
facility: Interni klinika - Oddeleni klin. hematologie Fakultni nemocnice Hradec Kralove
city: Praha
country: Czechia
facility: Oddeleni klinicke hematologie, Fakultni nemocnice Kralovske Vinohrady
city: Berlin
country: Germany
facility: Vivantes Klinikum Neukölln Klinik für Innere Medizin Hämatologie und Onkologie
city: Berlin
country: Germany
facility: Vivantes Klinikum Spandau Klinik für Innere Medizin - Hämatologie, Onkologie und Gastroenterologie
city: Frankfurt
country: Germany
facility: Städt. Kliniken Frankfurt-Hoechst Med. Klinik II - Hämatologie und Onkologie
city: Freiburg
country: Germany
facility: Tumorklinik SANAFONTIS Alpine GmbH
city: Goch
country: Germany
facility: Wilhelm-Anton-Hospital Goch gGmbH Klinik für Hämatologie und internistische Onkologie
city: Lemgo
country: Germany
facility: Klinikum Lippe-Lemgo Med. Klinik II - Hämatologie und Onkologie
city: Mainz
country: Germany
facility: Johannes-Gutenberg-Universität Mainz III. Med. Klinik
city: Trier
country: Germany
facility: Mutterhaus der Borromäerinnen Med. Klinik I
city: Villingen
country: Germany
facility: Schwarzwald-Baar-Kliniken Innere Med. II
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum, III. sz. Belgyogyaszati Klinika
city: Győr
country: Hungary
facility: Petz Aladár Kórház, II. Belgyógyászat
city: Kaposvar
country: Hungary
facility: Kaposi Mor Megyei Korhaz, Belgyogyaszat
city: Hyderabad 500033
country: India
facility: Apollo Hospital and Research Foundation, Apollo Hospitals
state: Andhra Pradesh
city: New Delhi- 110060
country: India
facility: Sir Ganga Ram Hospital
state: Delhi
city: Bangalore 560 029
country: India
facility: Kidwai Memorial Institute of Oncology
state: Karnataka
city: Thiruvananthapuram
country: India
facility: Regional Cancer Centre, Medical Oncology
state: Kerala-695011
city: Pune-411002
country: India
facility: Jehangir Hospital
state: Maharashtra
city: Chennai-600035
country: India
facility: Apollo Speciality Hospital, Chennai
state: Tamil Nadu
city: Kolkata- 700016
country: India
facility: Netaji Subash Chanda Bose Cancer Research Institute
state: West Bengal
city: Haifa
country: Israel
facility: Rambam Medical Center-Hematology department
city: Jerusalem
country: Israel
facility: Hadassah Medical Center - Hematology department
city: Petach Tiqva
country: Israel
facility: Rabin Medical Center, Beilinson Campus
city: Ramat-Gan
country: Israel
facility: Sheba Medical Center
city: Rechovot
country: Israel
facility: Kaplan Medical Center - Hematology Institute
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria di Bologna Policlinico S.Orsola-Malpighi Dipartimento di Ematologia e Scienze Oncologiche "L. e A. Seragnoli"
city: Brescia
country: Italy
facility: Spedali Civili di Brescia
city: Modena
country: Italy
facility: Dipartimento di Oncologia ed Ematologia Università di Modena e Reggio Emilia
city: Roma
country: Italy
facility: AZIENDA OSPEDALIERA UNIVERSITARIA POLICLINICO TOR VERGATA DIPARTIMENTO DI MEDICINA U.O.C. Ematologia
city: Torino
country: Italy
facility: Azienda Ospedaliera San Giovanni Battista "Molinette" Struttura Complessa Ematologia 2
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Pulau Pinang
country: Malaysia
facility: Gleneagles Medical Centre
city: Casablanca
country: Morocco
facility: Hopital Du 20 Aout 1953
city: Rabat
country: Morocco
facility: Centre D'oncologie Al Azhar
city: Rabat
country: Morocco
facility: Institut National D'oncologie
city: Quezon City
country: Philippines
facility: National Kidney and Transplant Institute
city: Quezon City
country: Philippines
facility: St Lukes Medical Center
city: Gdynia
country: Poland
facility: Szpital Morski im. PCK w Gdyni Gdynskie Centrum Onkologii Oddzial Chemioterapii
city: Lodz
country: Poland
facility: Klinika Hematologii Uniwersytetu Medycznego w Lodzi
city: Poznan
country: Poland
facility: "Katedra i Klinika Hematologii i Chorob Rozrostowych Ukladu Krwiotworczego
city: Wroclaw
country: Poland
facility: Klinika Hematologii Nowotworow Krwi i Transplantacji Szpiku Akademii Medycznej we Wroclawiu
city: Braga
country: Portugal
facility: Hospital Sao Marcos
city: Coimbra
country: Portugal
facility: Hospitais da Universidade de Coimbra
city: Lisboa
country: Portugal
facility: Hospital de Santa Maria
city: Porto
country: Portugal
facility: Instituto Portugues de Oncologia
city: Baia Mare
country: Romania
facility: Spitalul Judetean de Urgenta "Dr. Constantin Opris", Hematologie
city: Bucuresti
country: Romania
facility: Institutul Clinic Fundeni, Hematologie
city: Bucuresti
country: Romania
facility: Spitalul Clinic Coltea, Clinica Hematologie
city: Bucuresti
country: Romania
facility: Spitalul Clinic Universitar de Urgenta Bucuresti, Hematologie
city: Iasi
country: Romania
facility: Spitalul Clinic Judetean de Urgenta "Sf. Spiridon" Iasi, Oncologie Medicala
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Regional Clinical Hospital
city: Belgorod
country: Russian Federation
facility: Belgorod Regional Oncology Center
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Oncology Center
city: Ekaterinburg
country: Russian Federation
facility: Sverdlovsk Regional Oncology Dispensary
city: Izhevsk
country: Russian Federation
facility: 1st Republican Clinical Hospital of Udmurtia
city: Moscow
country: Russian Federation
facility: Cancer Research Center RAMS - N.N. Blokhin - Academy of Medical Science
city: Moscow
country: Russian Federation
facility: Hematology Scientific Center
city: Moscow
country: Russian Federation
facility: Moscow Regional Clinical Research Institute
city: Moscow
country: Russian Federation
facility: S.P. Botkin Moscow City Clinical Hospital
city: Nizhniy Novgorod
country: Russian Federation
facility: Nizhniy Novgorod Region Clinical Hospital
city: Obninsk
country: Russian Federation
facility: Medical Scientific Radiology - Center
city: Omsk
country: Russian Federation
facility: Omsk Regional Oncology Dispensary
city: Perm
country: Russian Federation
facility: Medical Sanitary Unit # 1
city: Petrozavodsk
country: Russian Federation
facility: Republikan Hospital named after V.A/ Baranov
city: Rostov-on-Don
country: Russian Federation
facility: Rostov Research Institute of Oncology
city: St Petersburg
country: Russian Federation
facility: City Clinical Oncology Dispensary
city: St-Petersburg
country: Russian Federation
facility: Central Res. Inst. of Roentgen-Radiology
city: St-Petersburg
country: Russian Federation
facility: Pavlov State Medical Univercity
city: St. Petersburg
country: Russian Federation
facility: Leningrad Region Clinical Hospital
city: St. Petersburg
country: Russian Federation
facility: St.-Petersburg Clinical Research Institute of Hematology and Transfusiology
city: Singapore
country: Singapore
facility: National Cancer Centre
city: Singapore
country: Singapore
facility: Singapore General Hospital - Hematology
city: Johannesburg
country: South Africa
facility: Chris Hani Baragwanath Hospital
state: Gauteng
city: Johannesburg
country: South Africa
facility: Medical Oncology Center of Rosebank
state: Gauteng
city: Johannesburg
country: South Africa
facility: University of the Witwatersrand Oncology
state: Gauteng
city: Pretoria
country: South Africa
facility: Pretoria Academic Hospital-Dr. Savage Road, 3rd Floor Radiotherapy Building, Prinshof
state: Gauteng
city: Durban
country: South Africa
facility: Dr AI Pirjol & Dr WM Szpak Inc.
state: Kwazulu Natal
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincial de Barcelona
city: Madrid
country: Spain
facility: Hospital de la Princesa
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario Salamanca
city: Tao-Yuan
country: Taiwan
facility: Chang Gung Memorial Hospital, Linkou
city: Bangkok
country: Thailand
facility: King Chulalongkorn Memorial Hospital
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital
city: Bangkok
country: Thailand
facility: Siriraj Hospital-Hematology Unit
city: Chiang Mai
country: Thailand
facility: Maharaj Nakorn Chiang Mai hospital - Faculty of Medicine
city: Sousse
country: Tunisia
facility: Hôpital Farhat Hached
city: Tunis
country: Tunisia
facility: Centre National de Greffe de Moelle osseuse
city: Tunis
country: Tunisia
facility: Hôpital Aziza Othmana
city: Tunis
country: Tunisia
facility: Institut Salah Azaiz
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty
city: Izmir
country: Turkey
facility: Dokuz Eylul University Med. Fac.
city: Cherkassy
country: Ukraine
facility: Cherkassy Regional Oncology Center, Dept. of Hematology
city: Dnepropetrovsk
country: Ukraine
facility: Dnepropetrovsk City Clinical Hospital #4, Regional Hematology Center
city: Donetsk
country: Ukraine
facility: Institute of Urgent and Recovery Surgery named after V.K.Gusaka of AMS of Ukraine, Haematology Dept.
city: Khmelnitsky
country: Ukraine
facility: Khmelnitskiy Regional Hospital, Hematology Department
city: Kiev
country: Ukraine
facility: National Cancer Institute, Department of chemotherapy of hemoblastosis
city: Lviv
country: Ukraine
facility: Institute of Blood Pathology and Transfusion Medicine, Lviv Clinical Hospital #5, Hematology Dept.
city: Simferopol
country: Ukraine
facility: Crimean Republic Clinical Oncology Dispensary, Haematology Department
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
citation: Robak T, Jin J, Pylypenko H, Verhoef G, Siritanaratkul N, Drach J, Raderer M, Mayer J, Pereira J, Tumyan G, Okamoto R, Nakahara S, Hu P, Appiani C, Nemat S, Cavalli F; LYM-3002 investigators. Frontline bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in transplantation-ineligible patients with newly diagnosed mantle cell lymphoma: final overall survival results of a randomised, open-label, phase 3 study. Lancet Oncol. 2018 Nov;19(11):1449-1458. doi: 10.1016/S1470-2045(18)30685-5. Epub 2018 Oct 19.
citation: Robak T, Huang H, Jin J, Zhu J, Liu T, Samoilova O, Pylypenko H, Verhoef G, Siritanaratkul N, Osmanov E, Pereira J, Mayer J, Hong X, Okamoto R, Pei L, Rooney B, van de Velde H, Cavalli F. Association between bortezomib dose intensity and overall survival in mantle cell lymphoma patients on frontline VR-CAP in the phase 3 LYM-3002 study. Leuk Lymphoma. 2019 Jan;60(1):172-179. doi: 10.1080/10428194.2017.1321750. Epub 2017 Jun 5.
citation: Verhoef G, Robak T, Huang H, Pylypenko H, Siritanaratkul N, Pereira J, Drach J, Mayer J, Okamoto R, Pei L, Rooney B, Cakana A, van de Velde H, Cavalli F. Association between quality of response and outcomes in patients with newly diagnosed mantle cell lymphoma receiving VR-CAP versus R-CHOP in the phase 3 LYM-3002 study. Haematologica. 2017 May;102(5):895-902. doi: 10.3324/haematol.2016.152496. Epub 2017 Feb 9.
citation: Robak T, Huang H, Jin J, Zhu J, Liu T, Samoilova O, Pylypenko H, Verhoef G, Siritanaratkul N, Osmanov E, Alexeeva J, Pereira J, Drach J, Mayer J, Hong X, Okamoto R, Pei L, Rooney B, van de Velde H, Cavalli F; LYM-3002 Investigators. Bortezomib-based therapy for newly diagnosed mantle-cell lymphoma. N Engl J Med. 2015 Mar 5;372(10):944-53. doi: 10.1056/NEJMoa1412096.