Mantle Cell LymphomaPhase 3NCT00722137
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
A Phase 3 study testing Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2 and Doxorubicin 50 mg/m^2 in people with Mantle Cell Lymphoma, run by Millennium Pharmaceuticals, Inc. at 150 sites in 29 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mantle Cell Lymphoma
- What is being tested?
- Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2 and Doxorubicin 50 mg/m^2
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 487 participants
- Where
- 150 sitesin 29 countries
- Study dates
- 1 May 2008to 17 Jun 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Show all 17Show fewer
- 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
Who cannot join
- 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.
Show all 12Show fewer
- 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.
Trial locations and contacts
150 sites in 29 countries.
150 sites in 29 countries
Russia20 sites
Arkhangelsk Regional Clinical Hospital
Arkhangelsk
Belgorod Regional Oncology Center
Belgorod
Chelyabinsk Regional Oncology Center
Chelyabinsk
1st Republican Clinical Hospital of Udmurtia
Izhevsk
Cancer Research Center RAMS - N.N. Blokhin - Academy of Medical Science
Moscow
Hematology Scientific Center
Moscow
Moscow Regional Clinical Research Institute
Moscow
S.P. Botkin Moscow City Clinical Hospital
Moscow
Nizhniy Novgorod Region Clinical Hospital
Nizhny Novgorod
Medical Scientific Radiology - Center
Obninsk
Omsk Regional Oncology Dispensary
Omsk
Medical Sanitary Unit # 1
Perm
Republikan Hospital named after V.A/ Baranov
Petrozavodsk
Rostov Research Institute of Oncology
Rostov-on-Don
Central Res. Inst. of Roentgen-Radiology
Saint Petersburg
City Clinical Oncology Dispensary
Saint Petersburg
Leningrad Region Clinical Hospital
Saint Petersburg
Pavlov State Medical Univercity
Saint Petersburg
St.-Petersburg Clinical Research Institute of Hematology and Transfusiology
Saint Petersburg
Sverdlovsk Regional Oncology Dispensary
Yekaterinburg
Brazil11 sites
Centro de Hematologia E Hemoterapia - Unicamp
Campinas
Fundacao Hospital Amaral Carvalho
Jaú
Hospital Nossa Senhora da Conceicao
Porto Alegre
Hospital Sao Lucas Puc-Rs
Porto Alegre
Inca - Instituto Nacional Do Cancêr
Rio de Janeiro
Centro de Estudos de Hematologia E Oncologia Da Fmabc
São Paulo
Fundacao Pio XII - Hospital de Cancer de Barretos
São Paulo
Hospital Ac Camargo
São Paulo
Hospital Alemao Oswaldo Cruz
São Paulo
Hospital das Clínicas da Faculdade de Medicina da USP
São Paulo
Santa Casa de Misericórida de São Paulo
São Paulo
United States9 sites
Cancer Outreach Associates, PC
Abingdon, Virginia, 24211
Sinai Hospital
Baltimore, Maryland, 21215
Legacy Pharma Research
Bismarck, North Dakota, 58501
Center for Cancer Care at Goshen Hospital
Goshen, Indiana, 46526
St. Francis Hosptial and Medical Center
Hartford, Connecticut, 06105
Capitol Comp. Cancer Center
Jefferson City, Missouri, 65109
Hematology-Oncology Associates of Northern NJ
Morristown, New Jersey, 07960
Division of Hematology and Oncology Vanderbilt University
Nashville, Tennessee, 37232
Nebraska Cancer Specialists
Omaha, Nebraska, 68114
Belgium9 sites
AZ Stuivenberg Oncologie/ Hematologie
Antwerp
AZ St Jan AV
Bruges
UZ Brussel Department Medical Oncology
Brussels
UZA Hematologie, 1e verdiep
Edegem
Universitair Ziekenhuis Gent - UZ GENT, Hematologie, 9K12IE 9de verdiep- polikliniek Hematologie
Ghent
UZ Leuven Gasthuisberg Hematologie
Leuven
C.H.R. Citadelle
Liège
Centre Hospitalier Universitaire
Liège
Ucl de Mont-Godinne
Yvoir
China9 sites
Beijing Cancer Hospital
Beijing
Cancer Institute & Cancer Hospital, CAMS&PUMC
Beijing
Peking University Third Hospital
Beijing
West China Hospital, Sichuan University
Chengdu, Sichuan
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong
Zhejiang University First Hospital
Hangzhou, Zhejiang
Cancer hospital, Fudan University
Shanghai
Ruijin Hospital
Shanghai
Tianjin Medical University Cancer Hospital and Institute
Tianjin
Germany9 sites
Vivantes Klinikum Neukölln Klinik für Innere Medizin Hämatologie und Onkologie
Berlin
Vivantes Klinikum Spandau Klinik für Innere Medizin - Hämatologie, Onkologie und Gastroenterologie
Berlin
Städt. Kliniken Frankfurt-Hoechst Med. Klinik II - Hämatologie und Onkologie
Frankfurt
Tumorklinik SANAFONTIS Alpine GmbH
Freiburg im Breisgau
Wilhelm-Anton-Hospital Goch gGmbH Klinik für Hämatologie und internistische Onkologie
Goch
Klinikum Lippe-Lemgo Med. Klinik II - Hämatologie und Onkologie
Lemgo
Johannes-Gutenberg-Universität Mainz III. Med. Klinik
Mainz
Mutterhaus der Borromäerinnen Med. Klinik I
Trier
Schwarzwald-Baar-Kliniken Innere Med. II
Villingen
India7 sites
Kidwai Memorial Institute of Oncology
Bangalore 560 029, Karnataka
Apollo Speciality Hospital, Chennai
Chennai-600035, Tamil Nadu
Apollo Hospital and Research Foundation, Apollo Hospitals
Hyderabad 500033, Andhra Pradesh
Netaji Subash Chanda Bose Cancer Research Institute
Kolkata- 700016, West Bengal
Sir Ganga Ram Hospital
New Delhi- 110060, National Capital Territory of Delhi
Jehangir Hospital
Pune-411002, Maharashtra
Regional Cancer Centre, Medical Oncology
Thiruvananthapuram, Kerala-695011
Ukraine7 sites
Cherkassy Regional Oncology Center, Dept. of Hematology
Cherkassy
Dnepropetrovsk City Clinical Hospital #4, Regional Hematology Center
Dnipro
Institute of Urgent and Recovery Surgery named after V.K.Gusaka of AMS of Ukraine, Haematology Dept.
Donetsk
Khmelnitskiy Regional Hospital, Hematology Department
Khmelnitsky
National Cancer Institute, Department of chemotherapy of hemoblastosis
Kiev
Institute of Blood Pathology and Transfusion Medicine, Lviv Clinical Hospital #5, Hematology Dept.
Lviv
Crimean Republic Clinical Oncology Dispensary, Haematology Department
Simferopol
Israel5 sites
Rambam Medical Center-Hematology department
Haifa
Hadassah Medical Center - Hematology department
Jerusalem
Rabin Medical Center, Beilinson Campus
Petach Tiqva
Sheba Medical Center
Ramat Gan
Kaplan Medical Center - Hematology Institute
Rehovot
Italy5 sites
Azienda Ospedaliera Universitaria di Bologna Policlinico S.Orsola-Malpighi Dipartimento di Ematologia e Scienze Oncologiche "L. e A. Seragnoli"
Bologna
Spedali Civili di Brescia
Brescia
Dipartimento di Oncologia ed Ematologia Università di Modena e Reggio Emilia
Modena
AZIENDA OSPEDALIERA UNIVERSITARIA POLICLINICO TOR VERGATA DIPARTIMENTO DI MEDICINA U.O.C. Ematologia
Roma
Azienda Ospedaliera San Giovanni Battista "Molinette" Struttura Complessa Ematologia 2
Torino
Romania5 sites
Spitalul Judetean de Urgenta "Dr. Constantin Opris", Hematologie
Baia Mare
Institutul Clinic Fundeni, Hematologie
Bucharest
Spitalul Clinic Coltea, Clinica Hematologie
Bucharest
Spitalul Clinic Universitar de Urgenta Bucuresti, Hematologie
Bucharest
Spitalul Clinic Judetean de Urgenta "Sf. Spiridon" Iasi, Oncologie Medicala
Iași
South Africa5 sites
Dr AI Pirjol & Dr WM Szpak Inc.
Durban, KwaZulu-Natal
Chris Hani Baragwanath Hospital
Johannesburg, Gauteng
Medical Oncology Center of Rosebank
Johannesburg, Gauteng
University of the Witwatersrand Oncology
Johannesburg, Gauteng
Pretoria Academic Hospital-Dr. Savage Road, 3rd Floor Radiotherapy Building, Prinshof
Pretoria, Gauteng
Spain5 sites
Hospital Universitario Germans Trias i Pujol
Badalona, Barcelona
Hospital Clinic I Provincial de Barcelona
Barcelona
Hospital de la Princesa
Madrid
Hospital Universitario 12 de Octubre
Madrid
Hospital Clinico Universitario Salamanca
Salamanca
Poland4 sites
Szpital Morski im. PCK w Gdyni Gdynskie Centrum Onkologii Oddzial Chemioterapii
Gdynia
Klinika Hematologii Uniwersytetu Medycznego w Lodzi
Lodz
"Katedra i Klinika Hematologii i Chorob Rozrostowych Ukladu Krwiotworczego
Poznan
Klinika Hematologii Nowotworow Krwi i Transplantacji Szpiku Akademii Medycznej we Wroclawiu
Wroclaw
Portugal4 sites
Hospital Sao Marcos
Braga
Hospitais da Universidade de Coimbra
Coimbra
Hospital de Santa Maria
Lisbon
Instituto Portugues de Oncologia
Porto
Thailand4 sites
King Chulalongkorn Memorial Hospital
Bangkok
Ramathibodi Hospital
Bangkok
Siriraj Hospital-Hematology Unit
Bangkok
Maharaj Nakorn Chiang Mai hospital - Faculty of Medicine
Chiang Mai
Tunisia4 sites
Hôpital Farhat Hached
Sousse
Centre National de Greffe de Moelle osseuse
Tunis
Hôpital Aziza Othmana
Tunis
Institut Salah Azaiz
Tunis
Chile3 sites
Hospital Clinico Universidad Catolica de Chile
Santiago
Hospital Del Salvador
Santiago
Instituto Nacional Del Cancer
Santiago
Colombia3 sites
Clinica Reina Sofia
Bogotá
Hospital Pablo Tobon Uribe
Medellín
Hospital Universitario San Vicente de Paul
Medellín
Czechia3 sites
Interni hematoonkoligicka klinika
Brno
Interni klinika - Oddeleni klin. hematologie Fakultni nemocnice Hradec Kralove
Hradec Králové
Oddeleni klinicke hematologie, Fakultni nemocnice Kralovske Vinohrady
Prague
Hungary3 sites
Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum, III. sz. Belgyogyaszati Klinika
Debrecen
Petz Aladár Kórház, II. Belgyógyászat
Győr
Kaposi Mor Megyei Korhaz, Belgyogyaszat
Kaposvár
Morocco3 sites
Hopital Du 20 Aout 1953
Casablanca
Centre D'oncologie Al Azhar
Rabat
Institut National D'oncologie
Rabat
Austria2 sites
St.Johanns Spital/Landeskrankenhaus Salzburg
Salzburg
Allgemeines Krankenhaus der Stadt Wien
Vienna
Canada2 sites
Cross Cancer Institute
Edmonton, Alberta
University Health Network, Princess Margaret Hospital
Toronto, Ontario
Malaysia2 sites
University Malaya Medical Centre
Kuala Lumpur
Gleneagles Medical Centre
Pulau Pinang
Philippines2 sites
National Kidney and Transplant Institute
Quezon City
St Lukes Medical Center
Quezon City
Singapore2 sites
National Cancer Centre
Singapore
Singapore General Hospital - Hematology
Singapore
Turkey (Türkiye)2 sites
Hacettepe University Medical Faculty
Ankara
Dokuz Eylul University Med. Fac.
Izmir
About this study
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
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.
Read the 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.
- Conditions
- Mantle Cell Lymphoma
- Being tested
- Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2, Doxorubicin 50 mg/m^2, VELCADE 1.3 mg/m^2, Prednisone 100 mg/m^2
- Medical subject headings
- Lymphoma, Mantle-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rituximab 375 mg/m^2Drug
Intravenous rituximab 375 mg/m^2 on Day 1 of a 21-day (3 week) cycle for 6 cycles.
Cyclophosphamide 750 mg/m^2Drug
Intravenous cyclophosphamide 750 mg/m^2 on Day 1 of a 21-day (3 week) cycle for 6 cycles
Doxorubicin 50 mg/m^2Drug
Intravenous doxorubicin 50 mg/m^2 on Day 1 of a 21-day (3 week) cycle for 6 cycles
VELCADE 1.3 mg/m^2Drug
Intravenous VELCADE 1.3 mg/m^2 on Days 1,4,8, and 11of a 21-day (3 week) cycle for 6 cycles
Prednisone 100 mg/m^2Drug
Oral prednisone 100 mg/m^2 on Day 1 to Day 5 of a 21-day (3 week) cycle for 6 cycles
Vincristine 1.4 mg/m^2Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| R-CHOP | Active comparator | 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 Receives: Drug: Rituximab 375 mg/m^2; Drug: Cyclophosphamide 750 mg/m^2; Drug: Doxorubicin 50 mg/m^2; Drug: Prednisone 100 mg/m^2; Drug: Vincristine 1.4 mg/m^2 |
| VcR-CAP | Experimental | 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 Receives: Drug: Rituximab 375 mg/m^2; Drug: Cyclophosphamide 750 mg/m^2; Drug: Doxorubicin 50 mg/m^2; Drug: VELCADE 1.3 mg/m^2; Drug: Prednisone 100 mg/m^2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS)
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.
Measured: Median duration of follow-up of 40 months
Secondary outcomes (10)
Time to Progression (TTP)
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.
Measured: Median duration of follow-up of 40 months
Duration of Response
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).
Measured: Median duration of follow-up of 40 months
Time to Next Anti-lymphoma Treatment (TTNT)
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.
Measured: : Median duration of follow-up of 40 months
Treatment-free Interval (TFI)
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.
Measured: Median duration of follow-up of 40 months
Overall Response Rate (ORR)
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.
Measured: Median duration of follow-up of 40 months
Overall Complete Response (CR + CRu)
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.
Measured: Median duration of follow-up of 40 months
Overall Survival (OS)
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.
Measured: Median duration of follow-up of 40 months
18-Month Survival
18-month survival was defined as the estimated probability of survival at 18 months (Kaplan-Meier estimate).
Measured: Up to month 18 from the time of randomization
Overall Survival (OS) in Long Term Follow-up Period
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.
Measured: Up to 107.4 months
Number of Participants Experiencing an Adverse Event (AE)
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.
Measured: Up to 107.4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2008 (estimated)
- Study start1 May 2008
- Primary completion1 Jan 2014
- Study completion17 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Mantle Cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 487 participants (actual)
Sponsor and investigators
- Lead sponsor
- Millennium Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
- Responsible party
- Sponsor
- Investigators
- Medical Director Clinical Science, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00722137
- Sponsor's protocol ID
- 26866138-LYM-3002
- Other IDs
- 26866138-LYM-3002CTIL, 2007-005669-37, 0970313683, U1111-1195-3827
- Status last verified
- Jun 2018
- First submitted
- 23 Jul 2008
- Last updated
- 12 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 30348538Robak 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.
PubMed 28583031Verhoef 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.
PubMed 28183846Robak 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.
PubMed 25738670
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00722137
- Acronym / sponsor ID
- 26866138-LYM-3002
- Conditions
- Mantle Cell Lymphoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 487 participants (actual)
- Lead sponsor
- Millennium Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
- Study start
- 1 May 2008 (actual)
- Primary completion
- 1 Jan 2014 (actual)
- Study completion
- 17 Jun 2017 (actual)
- First posted
- 25 Jul 2008 (estimated)
- Results
- Posted 17 Nov 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| R-CHOP | Active comparator | Drug: Rituximab 375 mg/m^2, Drug: Cyclophosphamide 750 mg/m^2, Drug: Doxorubicin 50 mg/m^2, Drug: Prednisone 100 mg/m^2, Drug: Vincristine 1.4 mg/m^2Rituximab 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 |
| VcR-CAP | Experimental | Drug: Rituximab 375 mg/m^2, Drug: Cyclophosphamide 750 mg/m^2, Drug: Doxorubicin 50 mg/m^2, Drug: VELCADE 1.3 mg/m^2, Drug: Prednisone 100 mg/m^2Rituximab 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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.
- 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).
Key exclusion criteria (12 listed)
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rituximab 375 mg/m^2Intravenous rituximab 375 mg/m^2 on Day 1 of a 21-day (3 week) cycle for 6 cycles. | Drug | R-CHOP, VcR-CAP |
| Cyclophosphamide 750 mg/m^2Intravenous cyclophosphamide 750 mg/m^2 on Day 1 of a 21-day (3 week) cycle for 6 cycles | Drug | R-CHOP, VcR-CAP |
| Doxorubicin 50 mg/m^2Intravenous doxorubicin 50 mg/m^2 on Day 1 of a 21-day (3 week) cycle for 6 cycles | Drug | R-CHOP, VcR-CAP |
| VELCADE 1.3 mg/m^2Intravenous VELCADE 1.3 mg/m^2 on Days 1,4,8, and 11of a 21-day (3 week) cycle for 6 cycles | Drug | VcR-CAP |
| Prednisone 100 mg/m^2Oral prednisone 100 mg/m^2 on Day 1 to Day 5 of a 21-day (3 week) cycle for 6 cycles | Drug | R-CHOP, VcR-CAP |
| Vincristine 1.4 mg/m^2Intravenous 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. | Drug | R-CHOP |
Primary outcome
Progression Free Survival (PFS)
Time frame: 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.
10 secondary outcomes
Time to Progression (TTP)
Time frame: Median duration of follow-up of 40 months
Duration of Response
Time frame: Median duration of follow-up of 40 months
Time to Next Anti-lymphoma Treatment (TTNT)
Time frame: : Median duration of follow-up of 40 months
Treatment-free Interval (TFI)
Time frame: Median duration of follow-up of 40 months
Overall Response Rate (ORR)
Time frame: Median duration of follow-up of 40 months
Overall Complete Response (CR + CRu)
Time frame: Median duration of follow-up of 40 months
Overall Survival (OS)
Time frame: Median duration of follow-up of 40 months
18-Month Survival
Time frame: Up to month 18 from the time of randomization
Overall Survival (OS) in Long Term Follow-up Period
Time frame: Up to 107.4 months
Number of Participants Experiencing an Adverse Event (AE)
Time frame: Up to 107.4 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30348538Robak 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.
- Derived from this study: PubMed 28583031Robak 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.
- Derived from this study: PubMed 28183846Verhoef 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.
- Derived from this study: PubMed 25738670Robak 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.
Related trials for Mantle Cell Lymphoma
Not yet recruitingPhase 1
Testing the Addition of an Anti-Cancer Drug, Glofitamab, to the Usual Chemotherapy Treatment (Alternating R-CHOP/R-DHAP) for Previously Untreated Mantle Cell Lymphoma
Ann Arbor Stage II Mantle Cell Lymphoma, Ann Arbor Stage III Mantle Cell Lymphoma
RecruitingPhase 3
A Study to Evaluate Glofitamab as a Single Agent vs. Investigator's Choice in Participants With Relapsed/Refractory Mantle Cell Lymphoma
Lymphoma
RecruitingPhase 1
A Study of LY4152199 in Participants With Previously Treated B-cell Malignancies (BAF_FRontier-1 )
Lymphoma, Non-Hodgkin, B-cell Lymphoma
RecruitingPhase 2
Auto Stem Cell Transplant for Lymphoma Patients
Non-Hodgkin Lymphoma, Hodgkin Lymphoma
Active, not recruitingPhase 1
Study to Evaluate Adverse Events, Change in Disease Activity, and How Oral ABBV-101 Moves Through the Body in Adult Participants With B-Cell Malignancies
Hematologic Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director Clinical Science study director
Takeda
150 sites in 29 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rituximab 375 mg/m^2, Cyclophosphamide 750 mg/m^2 and Doxorubicin 50 mg/m^2 in people with Mantle Cell Lymphoma, run by Millennium Pharmaceuticals, Inc. at 150 sites in 29 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 150 sites in Russia, Brazil, United States, Belgium, China and 24 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Nov 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (PFS) (time frame: Median duration of follow-up of 40 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00722137, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2018.