Clinical trial NCT01014208: Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant in Relapsed or Refractory Diffuse Large B Cell Lymphoma
Official title: Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant (ASCT) in Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
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
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
Nordic Lymphoma Group
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-11-16
Enrollment: 447
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This 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.

Eligibility 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.

Primary outcomes:
measure: Progression-free Survival as Assessed by Independent Reviewers
timeFrame: 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:
measure: Number of Participants With Overall Response (OR) and Complete Response (CR) After Salvage Chemoimmunotherapy
timeFrame: At completion of up to 3 cycles of salvage chemoimmunotherapy (assessed up to 9 weeks)
measure: Number of Participants With Overall Response (OR) and Complete Response (CR) Three Months After Autologous Stem Cell Transplant
timeFrame: At 3 months after completion of autologous stem cell transplantation (ASCT) (assessed up to 6 months)
measure: Event-free Survival
timeFrame: 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)
measure: Overall Survival (OS)
timeFrame: From randomization to death due to any cause (assessed for up to 5 years)
measure: Number of Participants With the Ability to Mobilize at Least 2 Million Cluster of Differentiation (CD)34+ Cells Per Kilogram From Peripheral Blood
timeFrame: During Cycles 2 and/or 3 (Weeks 4-9)
measure: Number of Participants Completing Autologous Stem Cell Transplant (ASCT)
timeFrame: Approximately 4 to 6 weeks following Cycle 3 (assessed up to 3 months)
measure: Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) During Treatment
timeFrame: Baseline and the end of the treatment period (until approximately 4 to 6 weeks following Cycle 3 [assessed up to 3 months])
measure: Change From Baseline in the Functional Assessment of Cancer Therapy Lymphoma Trial Outcome Index (FACT-Lym TOI) Total Score During Treatment
timeFrame: Baseline and the end of the treatment period (until approximately 4 to 6 weeks following Cycle 3 [assessed up to 3 months])
measure: Time to Neutrophil and Platelet Recovery After Each Cycle of Salvage Chemotherapy
timeFrame: 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)
measure: Time to Engraftment After High-dose Therapy (HDT)/ASCT
timeFrame: From ASCT up to 42 days post-ASCT (Baseline up to approximately 4.5 months)
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: GSK Investigational Site
state: California
city: New Haven
country: United States
facility: GSK Investigational Site
state: Connecticut
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Westwood
country: United States
facility: GSK Investigational Site
state: Kansas
city: Jackson
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facility: GSK Investigational Site
state: Mississippi
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Syracuse
country: United States
facility: GSK Investigational Site
state: New York
city: Chaple Hill
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Providence
country: United States
facility: GSK Investigational Site
state: Rhode Island
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facility: GSK Investigational Site
state: South Carolina
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facility: GSK Investigational Site
state: South Carolina
city: Nashville
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facility: GSK Investigational Site
state: Tennessee
city: San Antonio
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facility: GSK Investigational Site
state: Texas
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
city: Capital Federal
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: La Plata
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Graz
country: Austria
facility: GSK Investigational Site
city: Innsbruck
country: Austria
facility: GSK Investigational Site
city: Linz
country: Austria
facility: GSK Investigational Site
city: Linz
country: Austria
facility: GSK Investigational Site
city: Salzburg
country: Austria
facility: GSK Investigational Site
city: Wien
country: Austria
facility: GSK Investigational Site
city: Wien
country: Austria
facility: GSK Investigational Site
city: Brugge
country: Belgium
facility: GSK Investigational Site
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
city: Gent
country: Belgium
facility: GSK Investigational Site
city: Hasselt
country: Belgium
facility: GSK Investigational Site
city: Leuven
country: Belgium
facility: GSK Investigational Site
city: Yvoir
country: Belgium
facility: GSK Investigational Site
city: Fuzhou
country: China
facility: GSK Investigational Site
state: Fujian
city: Guangzhou
country: China
facility: GSK Investigational Site
state: Guangdong
city: Guangzhou
country: China
facility: GSK Investigational Site
state: Guangdong
city: Guangzhou
country: China
facility: GSK Investigational Site
state: Guangdong
city: Nanjing
country: China
facility: GSK Investigational Site
state: Jiangsu
city: Jianan
country: China
facility: GSK Investigational Site
state: Shandong
city: Hangzhou
country: China
facility: GSK Investigational Site
state: Zhejiang
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Chengdu
country: China
facility: GSK Investigational Site
city: Jiang Su Province
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Tianjin
country: China
facility: GSK Investigational Site
city: Brno
country: Czech Republic
facility: GSK Investigational Site
city: Hradec Kralove
country: Czech Republic
facility: GSK Investigational Site
city: Aarhus
country: Denmark
facility: GSK Investigational Site
city: Koebenhavn
country: Denmark
facility: GSK Investigational Site
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Tartu
country: Estonia
facility: GSK Investigational Site
city: Helsinki
country: Finland
facility: GSK Investigational Site
city: Oulu
country: Finland
facility: GSK Investigational Site
city: Tampere
country: Finland
facility: GSK Investigational Site
city: Ulm
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Aachen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Muenster
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Budapest
country: Hungary
facility: GSK Investigational Site
city: Budapest
country: Hungary
facility: GSK Investigational Site
city: Debrecen
country: Hungary
facility: GSK Investigational Site
city: Győr
country: Hungary
facility: GSK Investigational Site
city: Kaposvár
country: Hungary
facility: GSK Investigational Site
city: Szeged
country: Hungary
facility: GSK Investigational Site
city: Szombathely
country: Hungary
facility: GSK Investigational Site
city: Ludhiana
country: India
facility: GSK Investigational Site
city: Pune
country: India
facility: GSK Investigational Site
city: Vellore
country: India
facility: GSK Investigational Site
city: Dublin
country: Ireland
facility: GSK Investigational Site
city: Galway
country: Ireland
facility: GSK Investigational Site
city: James Street
country: Ireland
facility: GSK Investigational Site
city: Petach-Tikva
country: Israel
facility: GSK Investigational Site
city: Ramat Gan
country: Israel
facility: GSK Investigational Site
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Akita
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Ibaraki
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kyoto
country: Japan
facility: GSK Investigational Site
city: Miyagi
country: Japan
facility: GSK Investigational Site
city: Nagano
country: Japan
facility: GSK Investigational Site
city: Nagasaki
country: Japan
facility: GSK Investigational Site
city: Okayama
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Tochigi
country: Japan
facility: GSK Investigational Site
city: Tokushima
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Jellanamdo
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Amersfoort
country: Netherlands
facility: GSK Investigational Site
city: Amsterdam
country: Netherlands
facility: GSK Investigational Site
city: Amsterdam
country: Netherlands
facility: GSK Investigational Site
city: Amsterdam
country: Netherlands
facility: GSK Investigational Site
city: Den Haag
country: Netherlands
facility: GSK Investigational Site
city: Enschede
country: Netherlands
facility: GSK Investigational Site
city: Groningen
country: Netherlands
facility: GSK Investigational Site
city: Hoofddorp
country: Netherlands
facility: GSK Investigational Site
city: Leiden
country: Netherlands
facility: GSK Investigational Site
city: Maastricht
country: Netherlands
facility: GSK Investigational Site
city: Nieuwegein
country: Netherlands
facility: GSK Investigational Site
city: Nijmegen
country: Netherlands
facility: GSK Investigational Site
city: Rotterdam
country: Netherlands
facility: GSK Investigational Site
city: Rotterdam
country: Netherlands
facility: GSK Investigational Site
city: Rotterdam
country: Netherlands
facility: GSK Investigational Site
city: Sittard-geleen
country: Netherlands
facility: GSK Investigational Site
city: Utrecht
country: Netherlands
facility: GSK Investigational Site
city: Zwolle
country: Netherlands
facility: GSK Investigational Site
city: Oslo
country: Norway
facility: GSK Investigational Site
city: Chorzow
country: Poland
facility: GSK Investigational Site
city: Gdansk
country: Poland
facility: GSK Investigational Site
city: Poznan
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Wroclaw
country: Poland
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: St-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: St. Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Singapore
country: Singapore
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Majadahonda (Madrid)
country: Spain
facility: GSK Investigational Site
city: Murcia
country: Spain
facility: GSK Investigational Site
city: Pamplona
country: Spain
facility: GSK Investigational Site
city: Pozuelo de Alarcón/Madrid
country: Spain
facility: GSK Investigational Site
city: Salamanca
country: Spain
facility: GSK Investigational Site
city: Göteborg
country: Sweden
facility: GSK Investigational Site
city: Lund
country: Sweden
facility: GSK Investigational Site
city: Stockholm
country: Sweden
facility: GSK Investigational Site
city: Uppsala
country: Sweden
facility: GSK Investigational Site
city: Bangkok
country: Thailand
facility: GSK Investigational Site
city: Bangkok
country: Thailand
facility: GSK Investigational Site
city: Bangkok
country: Thailand
facility: GSK Investigational Site
city: Birmingham
country: United Kingdom
facility: GSK Investigational Site
city: Blackpool
country: United Kingdom
facility: GSK Investigational Site
city: Bristol
country: United Kingdom
facility: GSK Investigational Site
city: Cambridge
country: United Kingdom
facility: GSK Investigational Site
city: Cheltenham
country: United Kingdom
facility: GSK Investigational Site
city: Edinburgh
country: United Kingdom
facility: GSK Investigational Site
city: Glasgow
country: United Kingdom
facility: GSK Investigational Site
city: Headington, Oxford
country: United Kingdom
facility: GSK Investigational Site
city: Leeds
country: United Kingdom
facility: GSK Investigational Site
city: Liverpool
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Manchester
country: United Kingdom
facility: GSK Investigational Site
city: Manchester
country: United Kingdom
facility: GSK Investigational Site
city: Newcastle upon Tyne
country: United Kingdom
facility: GSK Investigational Site
city: Northwood
country: United Kingdom
facility: GSK Investigational Site
city: Nottingham
country: United Kingdom
facility: GSK Investigational Site
city: Sheffield
country: United Kingdom
facility: GSK Investigational Site
city: Southampton
country: United Kingdom
facility: GSK Investigational Site
city: Whitchurch, Cardiff
country: United Kingdom
facility: GSK Investigational Site
city: Wolverhampton
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: