Ofatumumab Bendamustine Combination Compared With Bendamustine Monotherapy in Indolent B-cell NHL Unresponsive to Rituxtherapy

NCT ID: NCT01077518

Last Updated: 2020-03-27

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

346 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-08-26

Study Completion Date

2018-12-26

Brief Summary

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The purpose of this study was to evaluate the safety and efficacy of ofatumumab and bendamustine combination therapy in patients with indolent B-cell NHL that did not respond to rituximab or a rituximab-containing regimen during or within 6 months of the last rituximab treatment.

Detailed Description

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Ofatumumab is an anti-CD20 monoclonal antibody shown to have monotherapy activity in patients with follicular lymphoma that has relapsed following rituximab-containing therapy. Bendamustine was approved by FDA for the treatment of in patients with indolent B-cell Non-Hodgkin's Lymphoma (NHL) that did not respond to rituximab or a rituximab-containing regimen during or within 6 months of the last rituximab treatment.

Biologics have demonstrated enhanced efficacy when added to chemotherapeutic combinations in the frontline treatment for indolent NHL. The combination of ofatumumab and bendamustine may provide additional clinical benefit and efficacy to those who no longer respond to rituximab or rituximab-containing regimens.

The objective of this study is to determine the effect of ofatumumab and bendamustine combination therapy in patients with indolent B-cell NHL that did not respond to rituximab or a rituximab-containing regimen during or within 6 months of the last rituximab treatment.

Conditions

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Lymphoma, Follicular

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

randomized open label bendamustine monotherapy vs. ofatumumab
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Ofatumumab and Bendamustine (Arm A)

Up to 8 cycles of bendamustine (90 mg/m2) on Days 1,2 every 21 days with12 doses of ofatumumab (1000 mg, Day 1 q21 days when with bendamustine and q28 days when given as monotherapy)

Group Type EXPERIMENTAL

Ofatumumab

Intervention Type DRUG

Ofatumumab was a liquid concentrate solution for infusion presented in glass vials containing 50 mL of solution at a concentration of 20 mg/mL to provide 1000 mg per vial. The ofatumumab infusions were prepared in 1000 mL sterile, pyrogen-free 0.9% NaCl to yield a 1 mg/mL ofatumumab concentration infusion.

Ofatumumab and Bendamustine infusions (Arm A)

Intervention Type DRUG

Up to 8 cycles of Bendamustine (90 mg/m2 Days 1 and 2, every 21 days) given in combination with 12 doses of ofatumumab (1000 mg). Ofatumumab will be given on day 1 of each cycle of bendamustine as long as patients in Arm A receive bendamustine. Once patients in Arm A complete bendamustine therapy, the remaining doses of ofatumumab will be given monthly until all 12 doses are completed.

Bendamustine (Arm B)

Up to 8 cycles of bendamustine (120 mg/m2) on Days 1,2 every 21 days

Group Type ACTIVE_COMPARATOR

Ofatumumab

Intervention Type DRUG

Ofatumumab was a liquid concentrate solution for infusion presented in glass vials containing 50 mL of solution at a concentration of 20 mg/mL to provide 1000 mg per vial. The ofatumumab infusions were prepared in 1000 mL sterile, pyrogen-free 0.9% NaCl to yield a 1 mg/mL ofatumumab concentration infusion.

Bendamustine infusion

Intervention Type DRUG

Bendamustine 100 mg/vial, injection

Bendamustine infusion (Arm B)

Intervention Type DRUG

Bendamustine (120 mg/m2 Days 1 and 2, every 21 days, up to 8 cycles).

Interventions

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Ofatumumab

Ofatumumab was a liquid concentrate solution for infusion presented in glass vials containing 50 mL of solution at a concentration of 20 mg/mL to provide 1000 mg per vial. The ofatumumab infusions were prepared in 1000 mL sterile, pyrogen-free 0.9% NaCl to yield a 1 mg/mL ofatumumab concentration infusion.

Intervention Type DRUG

Bendamustine infusion

Bendamustine 100 mg/vial, injection

Intervention Type DRUG

Ofatumumab and Bendamustine infusions (Arm A)

Up to 8 cycles of Bendamustine (90 mg/m2 Days 1 and 2, every 21 days) given in combination with 12 doses of ofatumumab (1000 mg). Ofatumumab will be given on day 1 of each cycle of bendamustine as long as patients in Arm A receive bendamustine. Once patients in Arm A complete bendamustine therapy, the remaining doses of ofatumumab will be given monthly until all 12 doses are completed.

Intervention Type DRUG

Bendamustine infusion (Arm B)

Bendamustine (120 mg/m2 Days 1 and 2, every 21 days, up to 8 cycles).

Intervention Type DRUG

Other Intervention Names

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OMB157

Eligibility Criteria

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Inclusion Criteria

* Indolent lymphoma including Grades 1-3a follicular, small lymphocytic, lymphoplasmacytic, and marginal zone lymphoma; Stages III-IV, or bulky disease, Stage II. Tumor verified CD20+ and CT imaging done at screening verifying disease
* Indolent B-cell NHL that remains stable or unresponsive during or within 6 months of treatment with rituximab or a rituximab-containing regimen
* Indolent lymphoma including grades 1-3a follicular, small lymphocytic, lymphoplasmacytic, and marginal zone lymphoma; stages III-IV, or bulky disease stage II (i.e. as any single mass \> 5 cm in any direction)
* ECOG Performance Status of 0, 1, or 2
* Life expectancy of at least 6 months
* 18 years or older
* Signed, written informed consent

Exclusion Criteria

* Grade 3b follicular lymphoma or evidence that the indolent lymphoma has transformed to aggressive lymphoma
* Previous allogeneic stem cell transplant
* Previous autologous stem cell transplant, fludarabine therapy, or radioimmunotherapy in the past 12 months
* Previous external beam radiation therapy to the pelvis. Previous external beam radiation therapy for bony disease to the cranium, mediastinum, and axilla, or to two or to more than 3 vertebral bodies
* High dose steroids greater to or equal to 60 mg prednisone/day (or equivalent) within 3 months of randomization. No more than 10 mg prednisone (or equivalent) daily at the time of randomization
* Prior bendamustine treatment within 1 year of randomization not resulting in a CR or PR for at least 6 months
* Treatment with anti-CD20 monoclonal antibody within 3 months of randomization
* Known CNS involvement of indolent lymphoma
* Other past or current malignancy. Subjects free of malignancy for at least 5 years or have history of definitively treated non-melanoma skin cancer, or successfully treated in situ carcinoma, are eligible
* Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment
* Clinically significant cardiac disease
* History of significant cerebrovascular disease or event with significant symptoms
* Positive serology for Hepatitis B
* Current active liver or biliary disease (except Gibber's syndrome or asymptomatic gallstones, liver metastases, or otherwise stable chronic liver disease)
* Known HIV positive
* Abnormal/inadequate blood values, liver and kidney function
* Current participation in other clinical study
* Inability to comply with the protocol activities
* Lactating or pregnant women or female patients of child-bearing potential (or male patients with such partners) not willing to use adequate contraception
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Novartis Investigative Site

Tucson, Arizona, United States

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Beverly Hills, California, United States

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Palm Springs, California, United States

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Washington D.C., District of Columbia, United States

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Atlanta, Georgia, United States

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Coeur d'Alene, Idaho, United States

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Silver Spring, Maryland, United States

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Detroit, Michigan, United States

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St Louis, Missouri, United States

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Mineola, New York, United States

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Rochester, New York, United States

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Danville, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Charleston, South Carolina, United States

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Nashville, Tennessee, United States

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Richmond, Virginia, United States

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Seattle, Washington, United States

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Morgantown, West Virginia, United States

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Capital Federal, Buenos Aires, Argentina

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Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

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Derqui, Pilar, Buenos Aires, Argentina

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La Plata, Buenos Aires, Argentina

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Buenos Aires, , Argentina

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Graz, , Austria

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Innsbruck, , Austria

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Leoben, , Austria

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Linz, , Austria

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Salzburg, , Austria

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Steyr, , Austria

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Vienna, , Austria

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Bruges, , Belgium

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Brussels, , Belgium

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Brussels, , Belgium

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Ghent, , Belgium

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Leuven, , Belgium

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Calgary, Alberta, Canada

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Halifax, Nova Scotia, Canada

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Barrie, Ontario, Canada

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Toronto, Ontario, Canada

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Saskatoon, Saskatchewan, Canada

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Avignon, , France

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Clermont-Ferrand, , France

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Grenoble, , France

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Tours, , France

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Mannheim, Baden-Wurttemberg, Germany

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Aschaffenburg, Bavaria, Germany

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Fürth, Bavaria, Germany

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Weilheim, Bavaria, Germany

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Frankfurt am Main, Hesse, Germany

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Giessen, Hesse, Germany

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Hanau, Hesse, Germany

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Kassel, Hesse, Germany

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Marburg, Hesse, Germany

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Bielefeld, North Rhine-Westphalia, Germany

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Essen, North Rhine-Westphalia, Germany

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Goch, North Rhine-Westphalia, Germany

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Herford, North Rhine-Westphalia, Germany

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Leverkusen, North Rhine-Westphalia, Germany

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Paderborn, North Rhine-Westphalia, Germany

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Recklinghausen, North Rhine-Westphalia, Germany

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Kaiserslautern, Rhineland-Palatinate, Germany

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Koblenz, Rhineland-Palatinate, Germany

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Neunkirchen, Saarland, Germany

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Berlin, , Germany

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Alexandroupoli, , Greece

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Haidari, Athens, , Greece

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Heraklion, Crete, , Greece

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Ioannina, , Greece

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Piraeus, , Greece

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Shatin, New Territories, , Hong Kong

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Tuenmen, , Hong Kong

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San Giovanni Rotondo, Apulia, Italy

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Reggio Calabria, Calabria, Italy

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Napoli, Campania, Italy

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Meldola (FC), Emilia-Romagna, Italy

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Aichi, , Japan

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Fukuoka, , Japan

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Hato Rey, , Puerto Rico

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Chelyabinsk, , Russia

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Kaluga, , Russia

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Moscow, , Russia

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Nizhny Novgorod, , Russia

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Novosibirsk, , Russia

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Penza, , Russia

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Saint Petersburg, , Russia

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St'Petersburg, , Russia

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Tula, , Russia

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Ufa, , Russia

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Volgograd, , Russia

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Bratislava, , Slovakia

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Kyiv, , Ukraine

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Lviv, , Ukraine

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Makiivka, , Ukraine

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Plymouth, Devon, United Kingdom

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Northwood, Middlesex, United Kingdom

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Harrow, , United Kingdom

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Southampton, , United Kingdom

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Uxbridge, , United Kingdom

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Countries

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United States Argentina Austria Belgium Canada France Germany Greece Hong Kong Italy Japan Poland Puerto Rico Russia Slovakia Ukraine United Kingdom

References

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Rummel MJ, Janssens A, MacDonald D, Keating MM, Zaucha JM, Davis J, Lasher J, Babanrao Pisal C, Izquierdo M, Friedberg JW. A phase 3, randomized study of ofatumumab combined with bendamustine in rituximab-refractory iNHL (COMPLEMENT A + B study). Br J Haematol. 2021 Jun;193(6):1123-1133. doi: 10.1111/bjh.17420. Epub 2021 May 10.

Reference Type DERIVED
PMID: 33973233 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2008-004177-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

COMB157E2301

Identifier Type: OTHER

Identifier Source: secondary_id

110918

Identifier Type: -

Identifier Source: org_study_id

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