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

NCT01014208 | Completed Phase 3 Results DMC

• 1 other identifier: 110928
• Study Type: interventional
• Target: 447
• Locations: 25 countries
• Sites: 171

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.

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

Outcome Measures

Primary Outcomes (1)

• 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).

  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

  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

  At 3 months after completion of autologous stem cell transplantation (ASCT) (assessed up to 6 months)

• Event-free Survival

  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)

  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

  During Cycles 2 and/or 3 (Weeks 4-9)

Study Arms (2)

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.

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.

Drug: RITUXIMAB + DHAP

Interventions

OFATUMUMAB + DHAP 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.

OFATUMUMAB + DHAP CHEMOTHERAPY REGIMEN

RITUXIMAB + DHAP 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.

RITUXIMAB + DHAP CHEMOTHERAPY REGIMEN

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (173)

GSK Investigational Site

Sacramento, California, 95816, United States

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GSK Investigational Site

New Haven, Connecticut, 06520, United States

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GSK Investigational Site

Chicago, Illinois, 60612-7323, United States

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GSK Investigational Site

Chicago, Illinois, 60637, United States

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GSK Investigational Site

Westwood, Kansas, 66205, United States

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GSK Investigational Site

Jackson, Mississippi, 39216-4505, United States

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GSK Investigational Site

New York, New York, 10065, United States

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GSK Investigational Site

Syracuse, New York, 13210, United States

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GSK Investigational Site

Chaple Hill, North Carolina, 27599-7305, United States

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GSK Investigational Site

Philadelphia, Pennsylvania, 19140, United States

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GSK Investigational Site

Providence, Rhode Island, 02908, United States

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GSK Investigational Site

Charleston, South Carolina, 29425, United States

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GSK Investigational Site

Greenville, South Carolina, 29601, United States

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GSK Investigational Site

Nashville, Tennessee, 37203, United States

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GSK Investigational Site

San Antonio, Texas, 78229, United States

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GSK Investigational Site

Seattle, Washington, 98108, United States

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GSK Investigational Site

Capital Federal, Buenos Aires, C1426ANZ, Argentina

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GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1431FWO, Argentina

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GSK Investigational Site

La Plata, Buenos Aires, B1900AXI, Argentina

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GSK Investigational Site

Graz, 8036, Austria

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GSK Investigational Site

Innsbruck, 6020, Austria

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GSK Investigational Site

Linz, 4020, Austria

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Linz, 4021, Austria

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Salzburg, A-5020, Austria

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GSK Investigational Site

Vienna, 1090, Austria

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GSK Investigational Site

Vienna, 1140, Austria

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GSK Investigational Site

Bruges, 8000, Belgium

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GSK Investigational Site

Brussels, 1200, Belgium

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GSK Investigational Site

Ghent, 9000, Belgium

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GSK Investigational Site

Hasselt, 3500, Belgium

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GSK Investigational Site

Leuven, 3000, Belgium

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GSK Investigational Site

Yvoir, 5530, Belgium

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GSK Investigational Site

Fuzhou, Fujian, 350014, China

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GSK Investigational Site

Guangzhou, Guangdong, 510060, China

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GSK Investigational Site

Guangzhou, Guangdong, 510080, China

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GSK Investigational Site

Guangzhou, Guangdong, 510515, China

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GSK Investigational Site

Nanjing, Jiangsu, 210029, China

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GSK Investigational Site

Jianan, Shandong, 250012, China

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GSK Investigational Site

Hangzhou, Zhejiang, 310003, China

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GSK Investigational Site

Beijing, 100021, China

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GSK Investigational Site

Beijing, 100044, China

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GSK Investigational Site

Beijing, 100071, China

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GSK Investigational Site

Beijing, 100142, China

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GSK Investigational Site

Beijing, 100191, China

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GSK Investigational Site

Beijing, 100730, China

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GSK Investigational Site

Beijing, 100853, China

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GSK Investigational Site

Chengdu, 610041, China

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GSK Investigational Site

Jiang Su Province, 215006, China

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GSK Investigational Site

Shanghai, 200025, China

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GSK Investigational Site

Shanghai, 200032, China

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GSK Investigational Site

Tianjin, 300020, China

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GSK Investigational Site

Brno, 625 00, Czechia

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GSK Investigational Site

Hradec Králové, Czechia

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GSK Investigational Site

Aarhus, 8000 C, Denmark

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GSK Investigational Site

Copenhagen, 2100, Denmark

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GSK Investigational Site

Tallinn, 13419, Estonia

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GSK Investigational Site

Tartu, 51014, Estonia

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GSK Investigational Site

Helsinki, 00029, Finland

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GSK Investigational Site

Oulu, 90029, Finland

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GSK Investigational Site

Tampere, 33520, Finland

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GSK Investigational Site

Ulm, Baden-Wurttemberg, 89081, Germany

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GSK Investigational Site

Aachen, North Rhine-Westphalia, 52074, Germany

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GSK Investigational Site

Münster, North Rhine-Westphalia, 48149, Germany

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Berlin, State of Berlin, 13353, Germany

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GSK Investigational Site

Athens, 11 527, Greece

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Athens, 11525, Greece

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GSK Investigational Site

Budapest, 1097, Hungary

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Budapest, 1122, Hungary

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Debrecen, 4012, Hungary

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GSK Investigational Site

Győr, 9023, Hungary

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GSK Investigational Site

Kaposvár, 7400, Hungary

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Szeged, 6720, Hungary

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GSK Investigational Site

Szombathely, 9700, Hungary

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GSK Investigational Site

Ludhiana, 141008, India

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Pune, 411001, India

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GSK Investigational Site

Vellore, 632004, India

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Dublin, 4, Ireland

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Galway, Ireland

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GSK Investigational Site

James Street, 8, Ireland

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GSK Investigational Site

Petah Tikva, 49100, Israel

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GSK Investigational Site

Ramat Gan, 52621, Israel

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GSK Investigational Site

Aichi, 466-8650, Japan

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GSK Investigational Site

Akita, 010-8543, Japan

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GSK Investigational Site

Fukuoka, 811-1395, Japan

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GSK Investigational Site

Hokkaido, 060-8648, Japan

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GSK Investigational Site

Hyōgo, 650-0047, Japan

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GSK Investigational Site

Ibaraki, 305-8576, Japan

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GSK Investigational Site

Kanagawa, 236-0004, Japan

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Kanagawa, 259-1143, Japan

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Kyoto, 602-8566, Japan

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GSK Investigational Site

Miyagi, 980-8574, Japan

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GSK Investigational Site

Nagano, 390-8621, Japan

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GSK Investigational Site

Nagasaki, 852-8501, Japan

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GSK Investigational Site

Okayama, 700-8558, Japan

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GSK Investigational Site

Osaka, 589-8511, Japan

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GSK Investigational Site

Tochigi, 329-0498, Japan

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GSK Investigational Site

Tokushima, 770-8503, Japan

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GSK Investigational Site

Tokyo, 104-0045, Japan

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GSK Investigational Site

Tokyo, 113-8655, Japan

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GSK Investigational Site

Tokyo, 135-8550, Japan

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GSK Investigational Site

Tokyo, 162-8655, Japan

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GSK Investigational Site

Amersfoort, 3818 ES, Netherlands

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Amsterdam, 1066 CX, Netherlands

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Amsterdam, 1081 HV, Netherlands

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Amsterdam, 1105 AZ, Netherlands

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GSK Investigational Site

Enschede, 7511JX, Netherlands

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GSK Investigational Site

Groningen, 9713 GZ, Netherlands

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Hoofddorp, 2134 TM, Netherlands

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Leiden, 2333 ZA, Netherlands

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Maastricht, 6229 HX, Netherlands

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GSK Investigational Site

Nieuwegein, 3435 CM, Netherlands

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GSK Investigational Site

Nijmegen, 6525 GA, Netherlands

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GSK Investigational Site

Rotterdam, 3015 CE, Netherlands

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Rotterdam, 3075 EA, Netherlands

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GSK Investigational Site

Rotterdam, 3079 DZ, Netherlands

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GSK Investigational Site

Sittard-geleen, 6162 BG, Netherlands

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The Hague, 2545 CH, Netherlands

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Utrecht, 3584 CX, Netherlands

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GSK Investigational Site

Zwolle, 8025 AB, Netherlands

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GSK Investigational Site

Oslo, 0310, Norway

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GSK Investigational Site

Chorzów, 41-500, Poland

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Gdansk, 80-952, Poland

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Poznan, 60-833, Poland

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Warsaw, 02-776, Poland

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Warsaw, 02-781, Poland

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Wroclaw, 50-367, Poland

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GSK Investigational Site

Moscow, 125101, Russia

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GSK Investigational Site

Saint Petersburg, 197022, Russia

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GSK Investigational Site

Saint Petersburg, 197110, Russia

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GSK Investigational Site

Singapore, 119074, Singapore

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GSK Investigational Site

Jellanamdo, 519-809, South Korea

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GSK Investigational Site

Seoul, 120-752, South Korea

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GSK Investigational Site

Seoul, 135-710, South Korea

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GSK Investigational Site

Barcelona, 08041, Spain

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GSK Investigational Site

Madrid, 28006, Spain

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GSK Investigational Site

Madrid, 28007, Spain

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GSK Investigational Site

Madrid, 28008, Spain

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GSK Investigational Site

Madrid, 28041, Spain

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GSK Investigational Site

Majadahonda (Madrid), 28222, Spain

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GSK Investigational Site

Murcia, 30120, Spain

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GSK Investigational Site

Pamplona, 31008, Spain

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GSK Investigational Site

Pozuelo de Alarcón/Madrid, 28223, Spain

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GSK Investigational Site

Salamanca, 37007, Spain

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Gothenburg, Sweden

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Lund, SE-221 85, Sweden

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GSK Investigational Site

Stockholm, SE-141 86, Sweden

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GSK Investigational Site

Uppsala, SE-751 85, Sweden

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GSK Investigational Site

Bangkok, 10330, Thailand

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GSK Investigational Site

Bangkok, 10400, Thailand

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GSK Investigational Site

Bangkok, 10700, Thailand

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GSK Investigational Site

Birmingham, B15 2TH, United Kingdom

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GSK Investigational Site

Blackpool, FY3 8NR, United Kingdom

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GSK Investigational Site

Bristol, BS2 8ED, United Kingdom

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GSK Investigational Site

Cambridge, CB2 2XY, United Kingdom

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GSK Investigational Site

Cheltenham, GL53 7AN, United Kingdom

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GSK Investigational Site

Edinburgh, EH4 2XU, United Kingdom

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GSK Investigational Site

Glasgow, G12 0YN, United Kingdom

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GSK Investigational Site

Headington, Oxford, OX3 7LE, United Kingdom

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GSK Investigational Site

Leeds, LS9 7TF, United Kingdom

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GSK Investigational Site

Liverpool, L7 8XP, United Kingdom

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GSK Investigational Site

London, NW1 2PG, United Kingdom

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GSK Investigational Site

London, NW3 2QG, United Kingdom

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GSK Investigational Site

London, SE5 9RS, United Kingdom

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GSK Investigational Site

London, W12 0HS, United Kingdom

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GSK Investigational Site

Manchester, M13 9WL, United Kingdom

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GSK Investigational Site

Manchester, M20 4BX, United Kingdom

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GSK Investigational Site

Newcastle upon Tyne, NE7 7DN, United Kingdom

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GSK Investigational Site

Northwood, HA6 2RN, United Kingdom

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GSK Investigational Site

Nottingham, NG5 1PB, United Kingdom

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GSK Investigational Site

Sheffield, S10 2JF, United Kingdom

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GSK Investigational Site

Southampton, SO16 6YD, United Kingdom

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GSK Investigational Site

Whitchurch, Cardiff, CF14 2TL, United Kingdom

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GSK Investigational Site

Wolverhampton, WV10 OQP, United Kingdom

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Neoplasms; Recurrence

Interventions

ofatumumab; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2009
• First Posted: November 16, 2009
• Study Start: March 1, 2010
• Primary Completion: February 1, 2014
• Study Completion: November 1, 2014
• Last Updated: August 7, 2015
• Results First Posted: October 16, 2014

Record last verified: 2015-02

Locations

CZ (2); SE (4); FI (3); AR (3); DK (2); AU (7); ES (10); GR (2); HU (7); DE (4); IL (2); KR (3); JP (20); NL (18); SG (1); CN (19); NO (1); GB (23); IN (3); US (16); TH (3); IE (3); BE (6); PL (6); RU (3)