Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant in Relapsed or Refractory Diffuse Large B Cell Lymphoma (ORCHARRD)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01014208
First received: November 4, 2009
Last updated: March 27, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Lymphoma, Large-Cell, Diffuse
Drug: OFATUMUMAB + DHAP
Drug: RITUXIMAB + DHAP
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant (ASCT) in Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Evaluate the progression-free survival (PFS) in subjects receiving ofatumumab in addition to salvage chemotherapy (O-chemo) compared to subjects receiving rituximab in addition to salvage chemotherapy (R-chemo) [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall and complete response rate after completion of salvage chemotherapy [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Ability to mobilize greater than or equal to 2X10^6 CD34+ cells/kg from peripheral blood. [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Safety, tolerability and health related quality of life measures [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Overall and complete response rate 3 months after ASCT [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Event-free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 410
Study Start Date: March 2010
Estimated Study Completion Date: November 2018
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: OFATUMUMAB + DHAP CHEMOTHERAPY REGIMEN
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.
Drug: OFATUMUMAB + DHAP
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.
Active Comparator: RITUXIMAB + DHAP CHEMOTHERAPY REGIMEN
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.
Drug: RITUXIMAB + DHAP
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • 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.

Exclusion Criteria:

  • 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01014208

  Hide Study Locations
Locations
United States, California
GSK Investigational Site
Sacramento, California, United States, 95816
United States, Connecticut
GSK Investigational Site
New Haven, Connecticut, United States, 06520
United States, Illinois
GSK Investigational Site
Chicago, Illinois, United States, 60637
GSK Investigational Site
Chicago, Illinois, United States, 60612-7323
United States, Kansas
GSK Investigational Site
Westwood, Kansas, United States, 66205
United States, Mississippi
GSK Investigational Site
Jackson, Mississippi, United States, 39216-4505
United States, New York
GSK Investigational Site
New York, New York, United States, 10065
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Syracuse, New York, United States, 13210
United States, North Carolina
GSK Investigational Site
Chaple Hill, North Carolina, United States, 27599-7305
United States, Pennsylvania
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19140
United States, Rhode Island
GSK Investigational Site
Providence, Rhode Island, United States, 02908
United States, South Carolina
GSK Investigational Site
Charleston, South Carolina, United States, 29425
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Greenville, South Carolina, United States, 29601
United States, Tennessee
GSK Investigational Site
Nashville, Tennessee, United States, 37203
United States, Texas
GSK Investigational Site
San Antonio, Texas, United States, 78229
United States, Washington
GSK Investigational Site
Seattle, Washington, United States, 98108
Argentina
GSK Investigational Site
Capital Federal, Buenos Aires, Argentina, C1426ANZ
GSK Investigational Site
Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1431FWO
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La Plata, Buenos Aires, Argentina, B1900AXI
Austria
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Graz, Austria, 8036
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Innsbruck, Austria, 6020
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Linz, Austria, 4021
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Linz, Austria, 4020
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Salzburg, Austria, A-5020
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Wien, Austria, 1140
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Wien, Austria, 1090
Belgium
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Brugge, Belgium, 8000
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Bruxelles, Belgium, 1200
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Gent, Belgium, 9000
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Hasselt, Belgium, 3500
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Leuven, Belgium, 3000
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Yvoir, Belgium, 5530
China, Fujian
GSK Investigational Site
Fuzhou, Fujian, China, 350014
China, Guangdong
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Guangzhou, Guangdong, China, 510060
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Guangzhou, Guangdong, China, 510515
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Guangzhou, Guangdong, China, 510080
China, Jiangsu
GSK Investigational Site
Nanjing, Jiangsu, China, 210029
China, Shandong
GSK Investigational Site
Jianan, Shandong, China, 250012
China, Zhejiang
GSK Investigational Site
Hangzhou, Zhejiang, China, 310003
China
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Beijing, China, 100071
GSK Investigational Site
Beijing, China, 100730
GSK Investigational Site
Beijing, China, 100853
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Beijing, China, 100021
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Beijing, China, 100044
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Beijing, China, 100191
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Beijing, China, 100142
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Chengdu, China, 610041
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Jiang Su Province, China, 215006
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Shanghai, China, 200032
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Shanghai, China, 200025
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Tianjin, China, 300020
Czech Republic
GSK Investigational Site
Brno, Czech Republic, 625 00
GSK Investigational Site
Hradec Kralove, Czech Republic
Denmark
GSK Investigational Site
Aarhus, Denmark, 8000 C
GSK Investigational Site
Koebenhavn, Denmark, 2100
Estonia
GSK Investigational Site
Tallinn, Estonia, 13419
GSK Investigational Site
Tartu, Estonia, 51014
Finland
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Helsinki, Finland, 00029
GSK Investigational Site
Oulu, Finland, 90029
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Tampere, Finland, 33520
Germany
GSK Investigational Site
Ulm, Baden-Wuerttemberg, Germany, 89081
GSK Investigational Site
Aachen, Nordrhein-Westfalen, Germany, 52074
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Muenster, Nordrhein-Westfalen, Germany, 48149
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Berlin, Germany, 13353
Greece
GSK Investigational Site
Athens, Greece, 11 527
GSK Investigational Site
Athens, Greece, 11525
Hungary
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Budapest, Hungary, 1097
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Budapest, Hungary, 1122
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Debrecen, Hungary, 4012
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Győr, Hungary, 9023
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Kaposvár, Hungary, 7400
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Szeged, Hungary, 6720
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Szombathely, Hungary, 9700
India
GSK Investigational Site
Ludhiana, India, 141008
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Pune, India, 411001
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Vellore, India, 632004
Ireland
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Dublin, Ireland, 4
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Galway, Ireland
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James Street, Ireland, 8
Israel
GSK Investigational Site
Petach-Tikva, Israel, 49100
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Ramat Gan, Israel, 52621
Japan
GSK Investigational Site
Aichi, Japan, 466-8650
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Akita, Japan, 010-8543
GSK Investigational Site
Fukuoka, Japan, 811-1395
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Hokkaido, Japan, 060-8648
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Hyogo, Japan, 650-0047
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Ibaraki, Japan, 305-8576
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Kanagawa, Japan, 259-1143
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Kanagawa, Japan, 236-0004
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Kyoto, Japan, 602-8566
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Miyagi, Japan, 980-8574
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Nagano, Japan, 390-8621
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Nagasaki, Japan, 852-8501
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Okayama, Japan, 700-8558
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Osaka, Japan, 589-8511
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Tochigi, Japan, 329-0498
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Tokushima, Japan, 770-8503
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Tokyo, Japan, 135-8550
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Tokyo, Japan, 113-8655
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Tokyo, Japan, 162-8655
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Tokyo, Japan, 104-0045
Korea, Republic of
GSK Investigational Site
Jellanamdo, Korea, Republic of, 519-809
GSK Investigational Site
Seoul, Korea, Republic of, 120-752
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Seoul, Korea, Republic of, 135-710
Netherlands
GSK Investigational Site
Amersfoort, Netherlands, 3818 ES
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Amsterdam, Netherlands, 1105 AZ
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Amsterdam, Netherlands, 1066 CX
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Amsterdam, Netherlands, 1081 HV
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Den Haag, Netherlands, 2545 CH
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Enschede, Netherlands, 7511JX
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Groningen, Netherlands, 9713 GZ
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Hoofddorp, Netherlands, 2134 TM
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Leiden, Netherlands, 2333 ZA
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Maastricht, Netherlands, 6229 HX
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Nieuwegein, Netherlands, 3435 CM
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Nijmegen, Netherlands, 6525 GA
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Rotterdam, Netherlands, 3015 CE
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Rotterdam, Netherlands, 3079 DZ
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Rotterdam, Netherlands, 3075 EA
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Sittard-geleen, Netherlands, 6162 BG
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Utrecht, Netherlands, 3584 CX
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Zwolle, Netherlands, 8025 AB
Norway
GSK Investigational Site
Oslo, Norway, 0310
Poland
GSK Investigational Site
Chorzow, Poland, 41-500
GSK Investigational Site
Gdansk, Poland, 80-952
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Poznan, Poland, 60-833
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Warszawa, Poland, 02-776
GSK Investigational Site
Warszawa, Poland, 02-781
GSK Investigational Site
Wroclaw, Poland, 50-367
Russian Federation
GSK Investigational Site
Moscow, Russian Federation, 125101
GSK Investigational Site
St-Petersburg, Russian Federation, 197110
GSK Investigational Site
St. Petersburg, Russian Federation, 197022
Singapore
GSK Investigational Site
Singapore, Singapore, 119074
Spain
GSK Investigational Site
Barcelona, Spain, 08041
GSK Investigational Site
Madrid, Spain, 28008
GSK Investigational Site
Madrid, Spain, 28007
GSK Investigational Site
Madrid, Spain, 28041
GSK Investigational Site
Madrid, Spain, 28006
GSK Investigational Site
Majadahonda (Madrid), Spain, 28222
GSK Investigational Site
Murcia, Spain, 30120
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Pamplona, Spain, 31008
GSK Investigational Site
Pozuelo de Alarcón/Madrid, Spain, 28223
GSK Investigational Site
Salamanca, Spain, 37007
Sweden
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Göteborg, Sweden
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Lund, Sweden, SE-221 85
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Stockholm, Sweden, SE-141 86
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Uppsala, Sweden, SE-751 85
Thailand
GSK Investigational Site
Bangkok, Thailand, 10330
GSK Investigational Site
Bangkok, Thailand, 10400
GSK Investigational Site
Bangkok, Thailand, 10700
United Kingdom
GSK Investigational Site
Birmingham, United Kingdom, B15 2TH
GSK Investigational Site
Blackpool, United Kingdom, FY3 8NR
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Bristol, United Kingdom, BS2 8ED
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Cambridge, United Kingdom, CB2 0QQ
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Cheltenham, United Kingdom, GL53 7AN
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Edinburgh, United Kingdom, EH4 2XU
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Glasgow, United Kingdom, G12 0YN
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Headington, Oxford, United Kingdom, OX3 7LJ
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Leeds, United Kingdom, LS9 7TF
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Liverpool, United Kingdom, L7 8XP
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London, United Kingdom, SE5 9RS
GSK Investigational Site
London, United Kingdom, NW1 2PG
GSK Investigational Site
London, United Kingdom, NW3 2QG
GSK Investigational Site
London, United Kingdom, W12 0HS
GSK Investigational Site
Manchester, United Kingdom, M13 9WL
GSK Investigational Site
Manchester, United Kingdom, M20 4BX
GSK Investigational Site
Newcastle upon Tyne, United Kingdom, NE7 7DN
GSK Investigational Site
Northwood, United Kingdom, HA6 2RN
GSK Investigational Site
Nottingham, United Kingdom, NG5 1PB
GSK Investigational Site
Sheffield, United Kingdom, S10 2JF
GSK Investigational Site
Southampton, United Kingdom, SO16 6YD
GSK Investigational Site
Whitchurch, Cardiff, United Kingdom, CF14 2TL
GSK Investigational Site
Wolverhampton, United Kingdom, WV10 OQP
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01014208     History of Changes
Other Study ID Numbers: 110928
Study First Received: November 4, 2009
Last Updated: March 27, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Polish Lymphoma Research Group
Japan Clinical Oncology Group
refractory
HOVON
DHAP
The All Ireland Cooperative Oncology Research Group
Oncology
Grupo Espanol de Linfomas
ofatumumab
Salvage chemotherapy
DVD
Nordic Lymphoma Group
rituximab
Autologous Stem Cell Transplant
GELTAMO
National Cancer Research Institute Lymphoma Clinical Studies Group
safety
Dutch-Belgian Cooperative Trial Group for Hematology-Oncology
Genmab
relapsed
efficacy

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 16, 2014