Lymphoma, Large-Cell, DiffusePhase 3ORCHARRDNCT01014208
Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant in Relapsed or Refractory Diffuse Large B Cell Lymphoma
A Phase 3 study testing OFATUMUMAB + DHAP and RITUXIMAB + DHAP in people with Lymphoma, Large-Cell, Diffuse, run by GlaxoSmithKline at 173 sites in 26 countries.
Trial summary
This study is being conducted to compare the efficacy and safety of ofatumumab in addition to salvage chemotherapy versus rituximab in addition to salvage chemotherapy in CD20 positive DLBCL subjects relapsing, or with persistent disease, after first-line treatment with rituximab combined with an anthracycline-based… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, Large-Cell, Diffuse
- What is being tested?
- OFATUMUMAB + DHAP and RITUXIMAB + DHAP
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 447 participants
- Where
- 173 sitesin 26 countries
- Study dates
- Mar 2010to Nov 2014
- 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
- Subjects with CD20 positive DLBCL or grade 3b follicular lymphoma (FL) at original diagnosis.
- Refractory to, or relapsed following, first-line treatment with rituximab combined with anthracycline- or anthracenedione-based chemotherapy as defined by the protocol.
- CT with involvement of 2 or more clearly demarcated lesions/ nodes with a long axis > 1.5 cm and short axis >= 1.0cm or 1 clearly demarcated lesion/ node with a long axis > 2.0 cm and short axis >= 1.0 cm.
- Baseline FDG-PET scans must demonstrate positive lesions compatible with CT defined anatomical tumor sites.
- Age 18 yrs or older.
- ECOG performance status of 0, 1 or 2.
Show all 9Show fewer
- Eligible for high dose chemotherapy and ASCT.
- Resolution of toxicities from first-line therapy to a grade that in the opinion of the investigator does not contraindicate study participation.
- Signed written informed consent.
Who cannot join
- Previous cancer therapy for lymphoma, with the exception of first-line rituximab/ anthracycline- or anthracenedione-based chemotherapy, monotherapy rituximab prior to or combined with first-line chemotherapy, as maintenance therapy, and radiotherapy in a limited field or as a part of the first-line treatment plan.
- Any anti-cancer therapy, except limited field radiotherapy, within 2 weeks prior to start of study therapy.
- Planned post-randomization chronic glucocorticoid use (limited acute use is allowed and defined by the protocol) unless administered as therapy for mild COPD or asthma.
- Clinically significant cardiac disease, active or chronic infections, serious significant diseases, other cancer within last 5 years. History of significant cerebrovascular disease.
- Prior treatment with anti-CD20 monoclonal antibodies with the exception of rituximab.
- Abnormal/ inadequate WBC count, liver, and kidney function.
- Pregnant or lactating women or female patients of child-bearing potential (or male patients with such partners) not willing to use adequate contraception during and up to 1 year following dosing completion.
Trial locations and contacts
173 sites in 26 countries.
173 sites in 26 countries
United Kingdom23 sites
GSK Investigational Site
Birmingham, B15 2TH
GSK Investigational Site
Blackpool, FY3 8NR
GSK Investigational Site
Bristol, BS2 8ED
GSK Investigational Site
Cambridge, CB2 2XY
GSK Investigational Site
Cheltenham, GL53 7AN
GSK Investigational Site
Edinburgh, EH4 2XU
GSK Investigational Site
Glasgow, G12 0YN
GSK Investigational Site
Headington, Oxford, OX3 7LE
GSK Investigational Site
Leeds, LS9 7TF
GSK Investigational Site
Liverpool, L7 8XP
GSK Investigational Site
London, NW1 2PG
GSK Investigational Site
London, NW3 2QG
GSK Investigational Site
London, SE5 9RS
GSK Investigational Site
London, W12 0HS
GSK Investigational Site
Manchester, M13 9WL
GSK Investigational Site
Manchester, M20 4BX
GSK Investigational Site
Newcastle upon Tyne, NE7 7DN
GSK Investigational Site
Northwood, HA6 2RN
GSK Investigational Site
Nottingham, NG5 1PB
GSK Investigational Site
Sheffield, S10 2JF
GSK Investigational Site
Southampton, SO16 6YD
GSK Investigational Site
Whitchurch, Cardiff, CF14 2TL
GSK Investigational Site
Wolverhampton, WV10 OQP
Japan20 sites
GSK Investigational Site
Aichi, 466-8650
GSK Investigational Site
Akita, 010-8543
GSK Investigational Site
Fukuoka, 811-1395
GSK Investigational Site
Hokkaido, 060-8648
GSK Investigational Site
Hyōgo, 650-0047
GSK Investigational Site
Ibaraki, 305-8576
GSK Investigational Site
Kanagawa, 236-0004
GSK Investigational Site
Kanagawa, 259-1143
GSK Investigational Site
Kyoto, 602-8566
GSK Investigational Site
Miyagi, 980-8574
GSK Investigational Site
Nagano, 390-8621
GSK Investigational Site
Nagasaki, 852-8501
GSK Investigational Site
Okayama, 700-8558
GSK Investigational Site
Osaka, 589-8511
GSK Investigational Site
Tochigi, 329-0498
GSK Investigational Site
Tokushima, 770-8503
GSK Investigational Site
Tokyo, 104-0045
GSK Investigational Site
Tokyo, 113-8655
GSK Investigational Site
Tokyo, 135-8550
GSK Investigational Site
Tokyo, 162-8655
China19 sites
GSK Investigational Site
Beijing, 100021
GSK Investigational Site
Beijing, 100044
GSK Investigational Site
Beijing, 100071
GSK Investigational Site
Beijing, 100142
GSK Investigational Site
Beijing, 100191
GSK Investigational Site
Beijing, 100730
GSK Investigational Site
Beijing, 100853
GSK Investigational Site
Chengdu, 610041
GSK Investigational Site
Fuzhou, Fujian, 350014
GSK Investigational Site
Guangzhou, Guangdong, 510060
GSK Investigational Site
Guangzhou, Guangdong, 510080
GSK Investigational Site
Guangzhou, Guangdong, 510515
GSK Investigational Site
Hangzhou, Zhejiang, 310003
GSK Investigational Site
Jianan, Shandong, 250012
GSK Investigational Site
Jiang Su Province, 215006
GSK Investigational Site
Nanjing, Jiangsu, 210029
GSK Investigational Site
Shanghai, 200025
GSK Investigational Site
Shanghai, 200032
GSK Investigational Site
Tianjin, 300020
Netherlands18 sites
GSK Investigational Site
Amersfoort, 3818 ES
GSK Investigational Site
Amsterdam, 1066 CX
GSK Investigational Site
Amsterdam, 1081 HV
GSK Investigational Site
Amsterdam, 1105 AZ
GSK Investigational Site
Enschede, 7511JX
GSK Investigational Site
Groningen, 9713 GZ
GSK Investigational Site
Hoofddorp, 2134 TM
GSK Investigational Site
Leiden, 2333 ZA
GSK Investigational Site
Maastricht, 6229 HX
GSK Investigational Site
Nieuwegein, 3435 CM
GSK Investigational Site
Nijmegen, 6525 GA
GSK Investigational Site
Rotterdam, 3015 CE
GSK Investigational Site
Rotterdam, 3075 EA
GSK Investigational Site
Rotterdam, 3079 DZ
GSK Investigational Site
Sittard-geleen, 6162 BG
GSK Investigational Site
The Hague, 2545 CH
GSK Investigational Site
Utrecht, 3584 CX
GSK Investigational Site
Zwolle, 8025 AB
United States16 sites
GSK Investigational Site
Chaple Hill, North Carolina, 27599-7305
GSK Investigational Site
Charleston, South Carolina, 29425
GSK Investigational Site
Chicago, Illinois, 60612-7323
GSK Investigational Site
Chicago, Illinois, 60637
GSK Investigational Site
Greenville, South Carolina, 29601
GSK Investigational Site
Jackson, Mississippi, 39216-4505
GSK Investigational Site
Nashville, Tennessee, 37203
GSK Investigational Site
New Haven, Connecticut, 06520
GSK Investigational Site
New York, New York, 10065
GSK Investigational Site
Philadelphia, Pennsylvania, 19140
GSK Investigational Site
Providence, Rhode Island, 02908
GSK Investigational Site
Sacramento, California, 95816
GSK Investigational Site
San Antonio, Texas, 78229
GSK Investigational Site
Seattle, Washington, 98108
GSK Investigational Site
Syracuse, New York, 13210
GSK Investigational Site
Westwood, Kansas, 66205
Spain10 sites
GSK Investigational Site
Barcelona, 08041
GSK Investigational Site
Madrid, 28006
GSK Investigational Site
Madrid, 28007
GSK Investigational Site
Madrid, 28008
GSK Investigational Site
Madrid, 28041
GSK Investigational Site
Majadahonda (Madrid), 28222
GSK Investigational Site
Murcia, 30120
GSK Investigational Site
Pamplona, 31008
GSK Investigational Site
Pozuelo de Alarcón/Madrid, 28223
GSK Investigational Site
Salamanca, 37007
Austria7 sites
GSK Investigational Site
Graz, 8036
GSK Investigational Site
Innsbruck, 6020
GSK Investigational Site
Linz, 4020
GSK Investigational Site
Linz, 4021
GSK Investigational Site
Salzburg, A-5020
GSK Investigational Site
Vienna, 1090
GSK Investigational Site
Vienna, 1140
Hungary7 sites
GSK Investigational Site
Budapest, 1097
GSK Investigational Site
Budapest, 1122
GSK Investigational Site
Debrecen, 4012
GSK Investigational Site
Győr, 9023
GSK Investigational Site
Kaposvár, 7400
GSK Investigational Site
Szeged, 6720
GSK Investigational Site
Szombathely, 9700
Belgium6 sites
GSK Investigational Site
Bruges, 8000
GSK Investigational Site
Brussels, 1200
GSK Investigational Site
Ghent, 9000
GSK Investigational Site
Hasselt, 3500
GSK Investigational Site
Leuven, 3000
GSK Investigational Site
Yvoir, 5530
Poland6 sites
GSK Investigational Site
Chorzów, 41-500
GSK Investigational Site
Gdansk, 80-952
GSK Investigational Site
Poznan, 60-833
GSK Investigational Site
Warsaw, 02-776
GSK Investigational Site
Warsaw, 02-781
GSK Investigational Site
Wroclaw, 50-367
Germany4 sites
GSK Investigational Site
Aachen, North Rhine-Westphalia, 52074
GSK Investigational Site
Berlin, State of Berlin, 13353
GSK Investigational Site
Münster, North Rhine-Westphalia, 48149
GSK Investigational Site
Ulm, Baden-Wurttemberg, 89081
Sweden4 sites
GSK Investigational Site
Gothenburg
GSK Investigational Site
Lund, SE-221 85
GSK Investigational Site
Stockholm, SE-141 86
GSK Investigational Site
Uppsala, SE-751 85
Argentina3 sites
GSK Investigational Site
Capital Federal, Buenos Aires, C1426ANZ
GSK Investigational Site
Ciudad Autonoma de Buenos Aires, Buenos Aires, C1431FWO
GSK Investigational Site
La Plata, Buenos Aires, B1900AXI
Finland3 sites
GSK Investigational Site
Helsinki, 00029
GSK Investigational Site
Oulu, 90029
GSK Investigational Site
Tampere, 33520
India3 sites
GSK Investigational Site
Ludhiana, 141008
GSK Investigational Site
Pune, 411001
GSK Investigational Site
Vellore, 632004
Ireland3 sites
GSK Investigational Site
Dublin, 4
GSK Investigational Site
Galway
GSK Investigational Site
James Street, 8
Russia3 sites
GSK Investigational Site
Moscow, 125101
GSK Investigational Site
Saint Petersburg, 197022
GSK Investigational Site
Saint Petersburg, 197110
South Korea3 sites
GSK Investigational Site
Jellanamdo, 519-809
GSK Investigational Site
Seoul, 120-752
GSK Investigational Site
Seoul, 135-710
Thailand3 sites
GSK Investigational Site
Bangkok, 10330
GSK Investigational Site
Bangkok, 10400
GSK Investigational Site
Bangkok, 10700
Czechia2 sites
GSK Investigational Site
Brno, 625 00
GSK Investigational Site
Hradec Králové
Denmark2 sites
GSK Investigational Site
Aarhus, 8000 C
GSK Investigational Site
Copenhagen, 2100
Estonia2 sites
GSK Investigational Site
Tallinn, 13419
GSK Investigational Site
Tartu, 51014
Greece2 sites
GSK Investigational Site
Athens, 11 527
GSK Investigational Site
Athens, 11525
Israel2 sites
GSK Investigational Site
Petah Tikva, 49100
GSK Investigational Site
Ramat Gan, 52621
About this study
Official title: Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant (ASCT) in Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)
This study is being conducted to compare the efficacy and safety of ofatumumab in addition to salvage chemotherapy versus rituximab in addition to salvage chemotherapy in CD20 positive DLBCL subjects relapsing, or with persistent disease, after first-line treatment with rituximab combined with an anthracycline-based chemotherapy regimen and be eligible for ASCT.
Read the detailed description
As rituximab-based regimens have become standard first-line treatment in CD20 positive DLBCL, the efficacy of rituximab combined with salvage chemotherapy in the second-line setting has decreased and there is a need for new therapies in patients progressing or relapsing after first-line rituximab-based therapy. Replacement of rituximab with ofatumumab in the second-line setting, following progression/relapse after first-line rituximab-containing regimens, offers the potential to overcome relative or complete rituximab resistance and thus improve response rates, the ability to proceed to consolidative HDT/ASCT, and overall survival.
- Conditions
- Lymphoma, Large-Cell, Diffuse
- Being tested
- OFATUMUMAB + DHAP, RITUXIMAB + DHAP
- Keywords
- The All Ireland Cooperative Oncology Research Group, GELTAMO, National Cancer Research Institute Lymphoma Clinical Studies Group, Genmab, ofatumumab, Japan Clinical Oncology Group, Oncology, Polish Lymphoma Research Group, Salvage chemotherapy, refractory, HOVON, DVD, relapsed, safety, efficacy, DHAP, rituximab, Autologous Stem Cell Transplant, Dutch-Belgian Cooperative Trial Group for Hematology-Oncology, Grupo Espanol de Linfomas
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Neoplasms, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OFATUMUMAB + DHAPDrug
3 cycles of treatment will be administered. Each cycle will last 21 days. ofatumumab dose: cycle 1, day 1 - 1000 mg; cycle 1, day 8 - 1000 mg; cycle 2, day 1 and cycle 3, day 1 - 1000 mg. DHAP regimen: dexamethasone - 40 mg on days 1, 2, 3, and 4 of dosing cycle; cisplatin - 100 mg/m2/24hrs continuous on day 1 of dosing cycle; cytarabine - 2g/m2 q12 hrs (2 doses) on day 2 of dosing cycle.
RITUXIMAB + DHAPDrug
3 cycles of treatment will be administered. Each cycle will last 21 days. rituximab dose: cycle 1, day 1 - 375 mg/m2; cycle 1, day 8 - 375 mg/m2; cycle 2, day 1 and cycle 3, day 1 - 375 mg/m2. DHAP regimen: dexamethasone - 40 mg on days 1, 2, 3, and 4 of dosing cycle; cisplatin - 100 mg/m2/24hrs continuous on day 1 of dosing cycle; cytarabine - 2g/m2 q12 hrs (2 doses) on day 2 of dosing cycle.
| Study group | Role | What they receive |
|---|---|---|
| OFATUMUMAB + DHAP CHEMOTHERAPY REGIMEN | Experimental | This study is a parallel arm study, with ofatumumab + DHAP. The Investigators are required to prospectively choose to treat all of their subjects with either DHAP chemotherapy regimens in combination with ofatumumab. All subjects will receive the same ofatumumab regimen and dose. Receives: Drug: OFATUMUMAB + DHAP |
| RITUXIMAB + DHAP CHEMOTHERAPY REGIMEN | Active comparator | This study is a parallel arm study, with rituximab + DHAP. The Investigators are required to prospectively choose to treat all of their subjects with either DHAP chemotherapy regimens in combination with rituximab. All subjects will receive the same rituximab regimen and dose. Receives: Drug: RITUXIMAB + DHAP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival as Assessed by Independent Reviewers
Progression-free survival is defined as the interval of time from the randomization date until the date of stable disease (SD; failure to attain the criteria needed for a CR or PR and no fulfillment of the criteria for progressive disease [PD]) after two cycles of salvage chemotherapy, progression, or death, whichever occurs first. Disease progression was based on the assessments of independent reviewers for the disease under study. Disease progression was based on imaging data via the Revised Response Criteria for Malignant Lymphoma (RRCML).
Measured: From randomization until the date of stable disease after two cycles of salvage chemotherapy, progression, or death (assessed for up to 5 years)
Secondary outcomes (10)
Number of Participants With Overall Response (OR) and Complete Response (CR) After Salvage Chemoimmunotherapy
OR is defined as the number of participants achieving either a complete response (CR) or a partial response (PR). CR is defined as the complete disappearance of all detectable clinical evidence of disease and disease-related symptoms. PR is defined as at least a 50% decrease from Baseline in the sum of the product of the diameters of target lesions. RRCML was used to assess CR and PR.
Measured: At completion of up to 3 cycles of salvage chemoimmunotherapy (assessed up to 9 weeks)
Number of Participants With Overall Response (OR) and Complete Response (CR) Three Months After Autologous Stem Cell Transplant
OR is defined as the number of participants achieving either a complete response (CR) or a partial response (PR). CR is defined as the complete disappearance of all detectable clinical evidence of disease and disease-related symptoms. PR is defined as at least a 50% decrease from Baseline in the sum of the product of the diameters of target lesions. RRCML was used to assess CR and PR.
Measured: At 3 months after completion of autologous stem cell transplantation (ASCT) (assessed up to 6 months)
Event-free Survival
Event-free survival is defined as the time from randomization to progressive disease (PD; disease whose course is growth, or spread of the disease), stable disease (SD; failure to attain the criteria needed for a CR or PR and no fulfillment of the criteria for PD) after completion of 2 cycles of therapy, commencement of a new treatment for diffuse large B cell lymphoma (DLBCL) (e.g., radiotherapy), or death from any cause, whichever occurs first. Disease progression was based on the assessments of independent reviewers for the disease under study. Disease progression was based on imaging data via the Revised Response Criteria for Malignant Lymphoma (RRCML).
Measured: From randomization to progressive disease, stable disease after completion of 2 cycles of therapy, commencement of a new treatment for DLBCL, or death due to any cause (assessed for up to 5 years)
Overall Survival (OS)
OS is defined as the time from randomization to death due to any cause. Participants who were still alive by the end of the study were censored.
Measured: From randomization to death due to any cause (assessed for up to 5 years)
Number of Participants With the Ability to Mobilize at Least 2 Million Cluster of Differentiation (CD)34+ Cells Per Kilogram From Peripheral Blood
Stem cell mobilization is the process of stimulating the hematopoietic stem cells (CD34+) to move out of the bone marrow and into the bloodstream, where they can be collected via a process called apheresis. Successful mobilization is defined as the collection of >2*10^6 CD34+ cells/kg. Only those participants, who commenced harvest, following the administration of rituximab or ofatumumab in combination with DHAP combination chemotherapy, were assessed. The number of participants with adequate harvest of CD34+ stem cells (at least 2*10^6 CD34+ cells/kg) after dosing of salvage therapy in Cycle 2 and Cycle 3 was analyzed.
Measured: During Cycles 2 and/or 3 (Weeks 4-9)
Number of Participants Completing Autologous Stem Cell Transplant (ASCT)
The number of participants who completed ASCT is reported.
Measured: Approximately 4 to 6 weeks following Cycle 3 (assessed up to 3 months)
Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) During Treatment
The FACT-G was developed by the Functional Assessment of Chronic Illness Therapy (FACIT) group for use in adults in a wide range of oncology clinical trial populations. The 27 items of the FACT-G are scored in the following domains: Physical Well-being (7 items), Social/Family Wellbeing (7 items), Emotional Well-being (6 items), and Functional Well-being (7 items). Participants responded to the items on a five-point Likert scale ranging from 0, "Not at all" to 4, "Very much." The total score ranges from 0 to 108; higher scores indicate a better patient-reported outcome/quality of life. Participants were asked to think back over the past week when responding to the items.
Measured: Baseline and the end of the treatment period (until approximately 4 to 6 weeks following Cycle 3 [assessed up to 3 months])
Change From Baseline in the Functional Assessment of Cancer Therapy Lymphoma Trial Outcome Index (FACT-Lym TOI) Total Score During Treatment
The FACT-Lym TOI is a measure that combines the FACT-Lym subscale (15 items; responses to each item range from 0, "Not at all" to 4, "Very much") with two domains taken from the FACT-G (responses to each item range from "Not at all " to "Very much"): Physical Well-being (7 items: lack of energy, nausea, meeting family needs, pain, side effects, feels ill, spends time in bed) and Functional Well-being (7 items: ability to work, work fulfilment, ability to enjoy life, illness acceptance, ability to sleep well, enjoying things done for fun, satisfaction with quality of life). This index is designed to be sensitive to changes in treatment regimens. The total FACT-Lym TOI score ranges from 0 to 116; higher scores indicate a better patient-reported outcome/quality of life. Participants were asked to think back over the past week when responding to the items.
Measured: Baseline and the end of the treatment period (until approximately 4 to 6 weeks following Cycle 3 [assessed up to 3 months])
Time to Neutrophil and Platelet Recovery After Each Cycle of Salvage Chemotherapy
Neutrophil (absolute neutrophil count [ANC]) recovery is defined as ANC >=0.5*10^9/Liter and increasing, and platelet (PLT) recovery is defined as PLT >=10*10^9/Liter and increasing. For each cycle, time to ANC recovery is defined as the time from the first dose to the first ANC >=0.5*10^9/Liter and increasing after the nadir in the cycle. For each cycle, time to PLT recovery is defined as the time from the first dose to the first PLT >=10*10^9/L and increasing after the nadir in the cycle.
Measured: From the start of each cycle for a maximum of 5 weeks per cycle (assessed during treatment period of Baseline up to approximately 3 months)
Time to Engraftment After High-dose Therapy (HDT)/ASCT
Engraftment is defined as 1) three consecutive days when the ANC is ≥0.5x109/L and 2) an unsupported platelet count of ≥20x109/L, and the engraftment date is the date that this occurs. If engraftment was not achieved by Day 42 or the last observation, engraftment was deemed to be a failure, and censoring took place at Day 42 or at the last observation.
Measured: From ASCT up to 42 days post-ASCT (Baseline up to approximately 4.5 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2009 (estimated)
- Study startMar 2010
- Primary completionFeb 2014
- Study completionNov 2014
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.
- Other trials for Lymphoma, Large-Cell, DiffuseStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- 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
- 447 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01014208
- Sponsor's protocol ID
- 110928
- Acronym
- ORCHARRD
- Status last verified
- Feb 2015
- First submitted
- 4 Nov 2009
- Last updated
- 7 Aug 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant (ASCT) in Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)
- ClinicalTrials.gov ID
- NCT01014208
- Acronym / sponsor ID
- ORCHARRD / 110928
- Conditions
- Lymphoma, Large-Cell, Diffuse
- Keywords
- The All Ireland Cooperative Oncology Research Group, GELTAMO, National Cancer Research Institute Lymphoma Clinical Studies Group, Genmab, ofatumumab, Japan Clinical Oncology Group, Oncology, Polish Lymphoma Research Group
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 447 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Mar 2010
- Primary completion
- Feb 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 16 Nov 2009 (estimated)
- Results
- Posted 16 Oct 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is being conducted to compare the efficacy and safety of ofatumumab in addition to salvage chemotherapy versus rituximab in addition to salvage chemotherapy in CD20 positive DLBCL subjects relapsing, or with persistent disease, after first-line treatment with rituximab combined with an anthracycline-based chemotherapy regimen and be eligible for ASCT.
Detailed description
As rituximab-based regimens have become standard first-line treatment in CD20 positive DLBCL, the efficacy of rituximab combined with salvage chemotherapy in the second-line setting has decreased and there is a need for new therapies in patients progressing or relapsing after first-line rituximab-based therapy. Replacement of rituximab with ofatumumab in the second-line setting, following progression/relapse after first-line rituximab-containing regimens, offers the potential to overcome relative or complete rituximab resistance and thus improve response rates, the ability to proceed to consolidative HDT/ASCT, and overall survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| OFATUMUMAB + DHAP CHEMOTHERAPY REGIMEN | Experimental | Drug: OFATUMUMAB + DHAPThis study is a parallel arm study, with ofatumumab + DHAP. The Investigators are required to prospectively choose to treat all of their subjects with either DHAP chemotherapy regimens in combination with ofatumumab. All subjects will receive the same ofatumumab regimen and dose. |
| RITUXIMAB + DHAP CHEMOTHERAPY REGIMEN | Active comparator | Drug: RITUXIMAB + DHAPThis study is a parallel arm study, with rituximab + DHAP. The Investigators are required to prospectively choose to treat all of their subjects with either DHAP chemotherapy regimens in combination with rituximab. All subjects will receive the same rituximab regimen and dose. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Subjects with CD20 positive DLBCL or grade 3b follicular lymphoma (FL) at original diagnosis.
- Refractory to, or relapsed following, first-line treatment with rituximab combined with anthracycline- or anthracenedione-based chemotherapy as defined by the protocol.
- CT with involvement of 2 or more clearly demarcated lesions/ nodes with a long axis > 1.5 cm and short axis >= 1.0cm or 1 clearly demarcated lesion/ node with a long axis > 2.0 cm and short axis >= 1.0 cm.
- Baseline FDG-PET scans must demonstrate positive lesions compatible with CT defined anatomical tumor sites.
- Age 18 yrs or older.
Key exclusion criteria (7 listed)
- Previous cancer therapy for lymphoma, with the exception of first-line rituximab/ anthracycline- or anthracenedione-based chemotherapy, monotherapy rituximab prior to or combined with first-line chemotherapy, as maintenance therapy, and radiotherapy in a limited field or as a part of the first-line treatment plan.
- Any anti-cancer therapy, except limited field radiotherapy, within 2 weeks prior to start of study therapy.
- Planned post-randomization chronic glucocorticoid use (limited acute use is allowed and defined by the protocol) unless administered as therapy for mild COPD or asthma.
- Clinically significant cardiac disease, active or chronic infections, serious significant diseases, other cancer within last 5 years. History of significant cerebrovascular disease.
- Prior treatment with anti-CD20 monoclonal antibodies with the exception of rituximab.
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 |
|---|---|---|
| OFATUMUMAB + DHAP3 cycles of treatment will be administered. Each cycle will last 21 days. ofatumumab dose: cycle 1, day 1 - 1000 mg; cycle 1, day 8 - 1000 mg; cycle 2, day 1 and cycle 3, day 1 - 1000 mg. DHAP regimen: dexamethasone - 40 mg on days 1, 2, 3, and 4 of dosing cycle; cisplatin - 100 mg/m2/24hrs continuous on day 1 of dosing cycle; cytarabine - 2g/m2 q12 hrs (2 doses) on day 2 of dosing cycle. | Drug | OFATUMUMAB + DHAP CHEMOTHERAPY REGIMEN |
| RITUXIMAB + DHAP3 cycles of treatment will be administered. Each cycle will last 21 days. rituximab dose: cycle 1, day 1 - 375 mg/m2; cycle 1, day 8 - 375 mg/m2; cycle 2, day 1 and cycle 3, day 1 - 375 mg/m2. DHAP regimen: dexamethasone - 40 mg on days 1, 2, 3, and 4 of dosing cycle; cisplatin - 100 mg/m2/24hrs continuous on day 1 of dosing cycle; cytarabine - 2g/m2 q12 hrs (2 doses) on day 2 of dosing cycle. | Drug | RITUXIMAB + DHAP CHEMOTHERAPY REGIMEN |
Primary outcome
Progression-free Survival as Assessed by Independent Reviewers
Time frame: From randomization until the date of stable disease after two cycles of salvage chemotherapy, progression, or death (assessed for up to 5 years)
Progression-free survival is defined as the interval of time from the randomization date until the date of stable disease (SD; failure to attain the criteria needed for a CR or PR and no fulfillment of the criteria for progressive disease [PD]) after two cycles of salvage chemotherapy, progression, or death, whichever occurs first. Disease progression was based on the assessments of independent reviewers for the disease under study. Disease progression was based on imaging data via the Revised Response Criteria for Malignant Lymphoma (RRCML).
10 secondary outcomes
Number of Participants With Overall Response (OR) and Complete Response (CR) After Salvage Chemoimmunotherapy
Time frame: At completion of up to 3 cycles of salvage chemoimmunotherapy (assessed up to 9 weeks)
Number of Participants With Overall Response (OR) and Complete Response (CR) Three Months After Autologous Stem Cell Transplant
Time frame: At 3 months after completion of autologous stem cell transplantation (ASCT) (assessed up to 6 months)
Event-free Survival
Time frame: From randomization to progressive disease, stable disease after completion of 2 cycles of therapy, commencement of a new treatment for DLBCL, or death due to any cause (assessed for up to 5 years)
Overall Survival (OS)
Time frame: From randomization to death due to any cause (assessed for up to 5 years)
Number of Participants With the Ability to Mobilize at Least 2 Million Cluster of Differentiation (CD)34+ Cells Per Kilogram From Peripheral Blood
Time frame: During Cycles 2 and/or 3 (Weeks 4-9)
Number of Participants Completing Autologous Stem Cell Transplant (ASCT)
Time frame: Approximately 4 to 6 weeks following Cycle 3 (assessed up to 3 months)
Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) During Treatment
Time frame: Baseline and the end of the treatment period (until approximately 4 to 6 weeks following Cycle 3 [assessed up to 3 months])
Change From Baseline in the Functional Assessment of Cancer Therapy Lymphoma Trial Outcome Index (FACT-Lym TOI) Total Score During Treatment
Time frame: Baseline and the end of the treatment period (until approximately 4 to 6 weeks following Cycle 3 [assessed up to 3 months])
Time to Neutrophil and Platelet Recovery After Each Cycle of Salvage Chemotherapy
Time frame: From the start of each cycle for a maximum of 5 weeks per cycle (assessed during treatment period of Baseline up to approximately 3 months)
Time to Engraftment After High-dose Therapy (HDT)/ASCT
Time frame: From ASCT up to 42 days post-ASCT (Baseline up to approximately 4.5 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
GSK Clinical Trials study director
GlaxoSmithKline
173 sites in 26 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing OFATUMUMAB + DHAP and RITUXIMAB + DHAP in people with Lymphoma, Large-Cell, Diffuse, run by GlaxoSmithKline at 173 sites in 26 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 9 inclusion and 7 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 7 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 173 sites in United Kingdom, Japan, China, Netherlands, United States and 21 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 16 Oct 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 as Assessed by Independent Reviewers (time frame: From randomization until the date of stable disease after two cycles of salvage chemotherapy, progression, or death (assessed for up to 5 years)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Aug 2015.