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

NCT ID: NCT01014208

Last Updated: 2015-08-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 447 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-31
• Study Completion Date: 2014-11-30

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.

Conditions

Lymphoma, Large-Cell, Diffuse

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

OFATUMUMAB + DHAP

Intervention Type: DRUG

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 + 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.

Group Type: ACTIVE_COMPARATOR

RITUXIMAB + DHAP

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Sacramento, California, United States

GSK Investigational Site

New Haven, Connecticut, United States

GSK Investigational Site

Chicago, Illinois, United States

GSK Investigational Site

Chicago, Illinois, United States

GSK Investigational Site

Westwood, Kansas, United States

GSK Investigational Site

Jackson, Mississippi, United States

GSK Investigational Site

New York, New York, United States

GSK Investigational Site

Syracuse, New York, United States

GSK Investigational Site

Chaple Hill, North Carolina, United States

GSK Investigational Site

Philadelphia, Pennsylvania, United States

GSK Investigational Site

Providence, Rhode Island, United States

GSK Investigational Site

Charleston, South Carolina, United States

GSK Investigational Site

Greenville, South Carolina, United States

GSK Investigational Site

Nashville, Tennessee, United States

GSK Investigational Site

San Antonio, Texas, United States

GSK Investigational Site

Seattle, Washington, United States

GSK Investigational Site

Capital Federal, Buenos Aires, Argentina

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

La Plata, Buenos Aires, Argentina

GSK Investigational Site

Graz, , Austria

GSK Investigational Site

Innsbruck, , Austria

GSK Investigational Site

Linz, , Austria

GSK Investigational Site

Linz, , Austria

GSK Investigational Site

Salzburg, , Austria

GSK Investigational Site

Vienna, , Austria

GSK Investigational Site

Vienna, , Austria

GSK Investigational Site

Bruges, , Belgium

GSK Investigational Site

Brussels, , Belgium

GSK Investigational Site

Ghent, , Belgium

GSK Investigational Site

Hasselt, , Belgium

GSK Investigational Site

Leuven, , Belgium

GSK Investigational Site

Yvoir, , Belgium

GSK Investigational Site

Fuzhou, Fujian, China

GSK Investigational Site

Guangzhou, Guangdong, China

GSK Investigational Site

Guangzhou, Guangdong, China

GSK Investigational Site

Guangzhou, Guangdong, China

GSK Investigational Site

Nanjing, Jiangsu, China

GSK Investigational Site

Jianan, Shandong, China

GSK Investigational Site

Hangzhou, Zhejiang, China

GSK Investigational Site

Beijing, , China

GSK Investigational Site

Beijing, , China

GSK Investigational Site

Beijing, , China

GSK Investigational Site

Beijing, , China

GSK Investigational Site

Beijing, , China

GSK Investigational Site

Beijing, , China

GSK Investigational Site

Beijing, , China

GSK Investigational Site

Chengdu, , China

GSK Investigational Site

Jiang Su Province, , China

GSK Investigational Site

Shanghai, , China

GSK Investigational Site

Shanghai, , China

GSK Investigational Site

Tianjin, , China

GSK Investigational Site

Brno, , Czechia

GSK Investigational Site

Hradec Králové, , Czechia

GSK Investigational Site

Aarhus, , Denmark

GSK Investigational Site

Copenhagen, , Denmark

GSK Investigational Site

Tallinn, , Estonia

GSK Investigational Site

Tartu, , Estonia

GSK Investigational Site

Helsinki, , Finland

GSK Investigational Site

Oulu, , Finland

GSK Investigational Site

Tampere, , Finland

GSK Investigational Site

Ulm, Baden-Wurttemberg, Germany

GSK Investigational Site

Aachen, North Rhine-Westphalia, Germany

GSK Investigational Site

Münster, North Rhine-Westphalia, Germany

GSK Investigational Site

Berlin, State of Berlin, Germany

GSK Investigational Site

Athens, , Greece

GSK Investigational Site

Athens, , Greece

GSK Investigational Site

Budapest, , Hungary

GSK Investigational Site

Budapest, , Hungary

GSK Investigational Site

Debrecen, , Hungary

GSK Investigational Site

Győr, , Hungary

GSK Investigational Site

Kaposvár, , Hungary

GSK Investigational Site

Szeged, , Hungary

GSK Investigational Site

Szombathely, , Hungary

GSK Investigational Site

Ludhiana, , India

GSK Investigational Site

Pune, , India

GSK Investigational Site

Vellore, , India

GSK Investigational Site

Dublin, , Ireland

GSK Investigational Site

Galway, , Ireland

GSK Investigational Site

James Street, , Ireland

GSK Investigational Site

Petah Tikva, , Israel

GSK Investigational Site

Ramat Gan, , Israel

GSK Investigational Site

Aichi, , Japan

GSK Investigational Site

Akita, , Japan

GSK Investigational Site

Fukuoka, , Japan

GSK Investigational Site

Hokkaido, , Japan

GSK Investigational Site

Hyōgo, , Japan

GSK Investigational Site

Ibaraki, , Japan

GSK Investigational Site

Kanagawa, , Japan

GSK Investigational Site

Kanagawa, , Japan

GSK Investigational Site

Kyoto, , Japan

GSK Investigational Site

Miyagi, , Japan

GSK Investigational Site

Nagano, , Japan

GSK Investigational Site

Nagasaki, , Japan

GSK Investigational Site

Okayama, , Japan

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Tochigi, , Japan

GSK Investigational Site

Tokushima, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Amersfoort, , Netherlands

GSK Investigational Site

Amsterdam, , Netherlands

GSK Investigational Site

Amsterdam, , Netherlands

GSK Investigational Site

Amsterdam, , Netherlands

GSK Investigational Site

Enschede, , Netherlands

GSK Investigational Site

Groningen, , Netherlands

GSK Investigational Site

Hoofddorp, , Netherlands

GSK Investigational Site

Leiden, , Netherlands

GSK Investigational Site

Maastricht, , Netherlands

GSK Investigational Site

Nieuwegein, , Netherlands

GSK Investigational Site

Nijmegen, , Netherlands

GSK Investigational Site

Rotterdam, , Netherlands

GSK Investigational Site

Rotterdam, , Netherlands

GSK Investigational Site

Rotterdam, , Netherlands

GSK Investigational Site

Sittard-geleen, , Netherlands

GSK Investigational Site

The Hague, , Netherlands

GSK Investigational Site

Utrecht, , Netherlands

GSK Investigational Site

Zwolle, , Netherlands

GSK Investigational Site

Oslo, , Norway

GSK Investigational Site

Chorzów, , Poland

GSK Investigational Site

Gdansk, , Poland

GSK Investigational Site

Poznan, , Poland

GSK Investigational Site

Warsaw, , Poland

GSK Investigational Site

Warsaw, , Poland

GSK Investigational Site

Wroclaw, , Poland

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Singapore, , Singapore

GSK Investigational Site

Jellanamdo, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Majadahonda (Madrid), , Spain

GSK Investigational Site

Murcia, , Spain

GSK Investigational Site

Pamplona, , Spain

GSK Investigational Site

Pozuelo de Alarcón/Madrid, , Spain

GSK Investigational Site

Salamanca, , Spain

GSK Investigational Site

Gothenburg, , Sweden

GSK Investigational Site

Lund, , Sweden

GSK Investigational Site

Stockholm, , Sweden

GSK Investigational Site

Uppsala, , Sweden

GSK Investigational Site

Bangkok, , Thailand

GSK Investigational Site

Bangkok, , Thailand

GSK Investigational Site

Bangkok, , Thailand

GSK Investigational Site

Birmingham, , United Kingdom

GSK Investigational Site

Blackpool, , United Kingdom

GSK Investigational Site

Bristol, , United Kingdom

GSK Investigational Site

Cambridge, , United Kingdom

GSK Investigational Site

Cheltenham, , United Kingdom

GSK Investigational Site

Edinburgh, , United Kingdom

GSK Investigational Site

Glasgow, , United Kingdom

GSK Investigational Site

Headington, Oxford, , United Kingdom

GSK Investigational Site

Leeds, , United Kingdom

GSK Investigational Site

Liverpool, , United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

Manchester, , United Kingdom

GSK Investigational Site

Manchester, , United Kingdom

GSK Investigational Site

Newcastle upon Tyne, , United Kingdom

GSK Investigational Site

Northwood, , United Kingdom

GSK Investigational Site

Nottingham, , United Kingdom

GSK Investigational Site

Sheffield, , United Kingdom

GSK Investigational Site

Southampton, , United Kingdom

GSK Investigational Site

Whitchurch, Cardiff, , United Kingdom

GSK Investigational Site

Wolverhampton, , United Kingdom

Countries

United States; Argentina; Austria; Belgium; China; Czechia; Denmark; Estonia; Finland; Germany; Greece; Hungary; India; Ireland; Israel; Japan; Netherlands; Norway; Poland; Russia; Singapore; South Korea; Spain; Sweden; Thailand; United Kingdom

Other Identifiers

110928

Identifier Type: -

Identifier Source: org_study_id