Ofatumumab Added to Fludarabine-Cyclophosphamide vs Fludarabine-Cyclophosphamide Combination in Relapsed Subjects With Chronic Lymphocytic Leukemia

NCT00824265 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 110913
• Study Type: interventional
• Target: 365
• Locations: 18 countries
• Sites: 135

Brief Summary

The purpose of this study was to evaluate the safety and efficacy of ofatumumab added to fludarabine-cyclophosphamide in patients with relapsed Chronic Lymphocytic Leukemia (CLL).

Conditions

Leukaemia, Lymphocytic, Chronic

Keywords

Relapsed; Oncology; Safety; Chronic Lymphocytic Leukemia; Ofatumumab; Efficacy

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS), as Assessed by the Independent Review Committee (IRC)

  PFS is defined as the interval of time between the date of randomization and the earlier of the date of disease progression (progressive disease,PD) and the date of death due to any cause. PD requires at least one of the following: lymphadenopathy, appearance of any new lesion such as enlargerd lymph nodes (\>1.5 cm) spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site; an increase by 50% or more in the previously noted enlargement of the liver or spleen, an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter, transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukaemia (CLL).

  From randomization up to 5 years after last dose of study drug

Secondary Outcomes (28)

• Overall Survival (OS)

  From randomization up to 5 years after last dose of study drug

• Time to Response, as Assessed by the IRC

  From randomization up to 5 years after last dose of study drug

• Duration of Response (DOR), as Assessed by the IRC

  From time of initial response to disease progression or death, whichever came first (up to 5 years after the last dose of study drug)

• Time to Progression, as Assessed by the IRC

  From randomization up to 5 years after the last dose of study drug

• Time to Next Therapy

  From the start of study drug until the start of the next anti-CLL therapy (up to 5 years after the last dose of study drug)

Study Arms (2)

Ofatumumab, Fludarabine, Cyclophosphamide

EXPERIMENTAL

Ofatumumab Cycle 1-Day 1 300mg, Cycle 1-Day 8 1000mg, then Cycles 2-6 Day 1 1000mg every 28 days, Fludarabine 25mg/m2 Days 1-3 every 28 days for 6 cycles, Cyclophosphamide 250 mg/m2 Days 1-3 every 28 days for 6 cycles

Drug: OFC Infusion

Fludarabine, Cyclophosphamide

ACTIVE COMPARATOR

Fludarabine 25mg/m2 Days 1-3 every 28 days for 6 cycles, Cyclophosphamide 250 mg/m2 Days 1-3 every 28 days for 6 cycles

Drug: FC infusion

Interventions

OFC Infusion DRUG

Ofatumumab Cycle 1-Day 1 300mg, Cycle 1-Day 8 1000mg, then Cycles 2-6 Day 1 1000mg every 28 days, Fludarabine 25mg/m2 Days 1-3 every 28 days for 6 cycles, Cyclophosphamide 250 mg/m2 Days 1-3 every 28 days for 6 cycles

Ofatumumab, Fludarabine, Cyclophosphamide

FC infusion DRUG

Fludarabine 25mg/m2 Days 1-3 every 28 days for 6 cycles, Cyclophosphamide 250mg/m2 Days 1-3 every 28 days for 6 cycles

Fludarabine, Cyclophosphamide

Eligibility Criteria

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

You may qualify if:

• confirmed and active CLL requiring treatment
• at least one previous treatment for CLL and having achieved a complete or partial remission/response but after a period of 6 or more months, shows evidence of disease progression
• fully active at a minimum or fully capable of selfcare and up and about more than 50% of waking hours
• age 18yrs or older
• signed written informed consent

You may not qualify if:

• diagnosis of refractory CLL (failure to achieve a complete or partial remission/response or disease progression within 6 months of last anti-CLL treatment
• abnormal/inadequate blood values, liver and kidney function
• certain heart problems, serious significant diseases, AIHA, other current cancers or within the last 5 years
• active or chronic infections
• use of drugs to suppress allergic or inflammatory responses (glucocorticoids)
• CLL transformation
• CLL central nervous system involvement
• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (135)

Novartis Investigative Site

Boca Raton, Florida, 33486, United States

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Novartis Investigative Site

Chicago, Illinois, 60612-3833, United States

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Clinton, Maryland, 20735, United States

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Kansas City, Missouri, 64128, United States

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St Louis, Missouri, 63110, United States

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Memphis, Tennessee, 38120, United States

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Novartis Investigative Site

Brasilia, Goiás, 70390-150, Brazil

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Porto Alegre, Rio Grande do Sul, 90610000, Brazil

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Novartis Investigative Site

São Paulo, São Paulo, 05403-000, Brazil

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Novartis Investigational Site

Porto Alegre, 91350, Brazil

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Novartis Investigative Site

Rio de Janeiro, 20211-030, Brazil

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Novartis Investigation Site

Rio de Janeiro, 20230-130, Brazil

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Novartis Investigative Site

Rio de Janeiro, 21941-913, Brazil

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Novartis Investigational Site

São Paulo, 03102-002, Brazil

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Novartis Investigative Site

Pleven, 5800, Bulgaria

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Plovdiv, 4000, Bulgaria

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Sofia, 1233, Bulgaria

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Sofia, 1407, Bulgaria

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Sofia, 1606, Bulgaria

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Sofia, Bulgaria

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Varna, 9010, Bulgaria

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New Westminster, British Columbia, V3L 3W4, Canada

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Kitchener, Ontario, N2G 1G3, Canada

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Newmarket, Ontario, L3Y 2P9, Canada

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Ottawa, Ontario, K1H 8L6, Canada

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Greenfield Park, Quebec, J4V 2H1, Canada

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Montreal, Quebec, H1T 2M4, Canada

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Sherbrooke, Quebec, J1H 5N4, Canada

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Saskatoon, Saskatchewan, S7N 4H4, Canada

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Novartis Investigative Site

Karlsruhe, Baden-Wurttemberg, 76137, Germany

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Stuttgart, Baden-Wurttemberg, 70190, Germany

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Stuttgart, Baden-Wurttemberg, 70376, Germany

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Villingen-Schwenningen, Baden-Wurttemberg, 78052, Germany

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Munich, Bavaria, 81241, Germany

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Frankfurt am Main, Hesse, 65929, Germany

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Kassel, Hesse, 34119, Germany

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Hanover, Lower Saxony, 30625, Germany

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Lehrte, Lower Saxony, 31275, Germany

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Essen, North Rhine-Westphalia, 45122, Germany

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Moenchengladbach-Rheydt, North Rhine-Westphalia, 41239, Germany

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Münster, North Rhine-Westphalia, 48149, Germany

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Saarbrücken, Saarland, 66113, Germany

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Dresden, Saxony, 01307, Germany

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Hamburg, 22767, Germany

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Lübeck, 23562, Germany

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Athens, 11 527, Greece

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Athens, 11527, Greece

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Novartis Investigative Site

Thessaloniki, 564 29, Greece

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Thessaloniki, 57010, Greece

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Bangalore, 560029, India

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Mumbai, 400012, India

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Mumbai, 400014, India

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New Delhi, 110029, India

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Pune, 411001, India

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Vadodara, 390007, India

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Potenza, Basilicate, 85100, Italy

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Rome, Lazio, 00041, Italy

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Rome, Lazio, 00161, Italy

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Genoa, Liguria, 16132, Italy

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Pavia, Lombardy, 27100, Italy

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Alessandria, Piedmont, 15100, Italy

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Novara, Piedmont, 28100, Italy

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Catania, Sicily, 95124, Italy

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Palermo, Sicily, 90146, Italy

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Ascoli Piceno, The Marches, 63100, Italy

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Guadalajara, Jalisco, 44280, Mexico

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Monterrey, Nuevo León, 64460, Mexico

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Monterrey, Nuevo León, 64710, Mexico

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Mexico City, CP 14080, Mexico

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Amersfoort, 3818 ES, Netherlands

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Nijmegen, 6525 GA, Netherlands

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Rotterdam, 3015 CE, Netherlands

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Rotterdam, 3075 EA, Netherlands

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The Hague, 2545 CH, Netherlands

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Bialystok, 15-276, Poland

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Chorzów, 41-500, Poland

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Krakow, 31-501, Poland

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Lodz, 93-510, Poland

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Opole, 45-372, Poland

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Szczecin, 71-242, Poland

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Słupsk, 76-200, Poland

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Warsaw, 02-507, 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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Novartis Investigative Site

Bucharest, 022328, Romania

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Bucharest, 050098, Romania

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Unknown Facility

Iași, 300328, Romania

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Novartis Investigative Site

Iași, 700483, Romania

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Novartis Investigative Site

Kazan', 420029, Russia

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Moscow, 115478, Russia

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Moscow, 125101, Russia

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Moscow, 125167, Russia

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Novosibirsk, 630087, Russia

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Saint Petersburg, 197 089, Russia

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St'Petersburg, 191024, Russia

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Barcelona, 08003, Spain

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Barcelona, 08025, Spain

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Barcelona, 08916, Spain

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Madrid, 28006, Spain

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Madrid, 28040, Spain

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Madrid, 28046, Spain

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Salamanca, 37007, Spain

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Seville, 41014, Spain

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Taichung, 404, Taiwan

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Taipei, 100, Taiwan

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Taipei, 112, Taiwan

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Taipei, 404, Taiwan

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Bangkok, 10330, Thailand

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Bangkok, 10400, Thailand

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Bangkok, 10700, Thailand

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Cherkasy, 18009, Ukraine

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Dnipropetrovsk, 49102, Ukraine

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Kharkiv, 61070, Ukraine

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Khmelnytskyi, 29000, Ukraine

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Kyiv, 03022, Ukraine

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Kyiv, 04112, Ukraine

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Lviv, 79044, Ukraine

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Makiivka, 86132, Ukraine

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Simferopil, 95023, Ukraine

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Vinnitsa, 21018, Ukraine

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Zhytomyr, 10002, Ukraine

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Birmingham, B9 5SS, United Kingdom

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Bradford, BD96RJ, United Kingdom

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Burton-on-Trent, DE13 0RB, United Kingdom

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Cottingham, HU16 5JQ, United Kingdom

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Dudley, DY1 2HQ, United Kingdom

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Glasgow, G12 OYN, United Kingdom

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Leicester, LE1 5WW, United Kingdom

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London, SE5 9RS, United Kingdom

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Manchester, M13 9WL, United Kingdom

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Sutton, SM5 1AA, United Kingdom

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Swindon, SN3 6BB, United Kingdom

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Truro, TR1 3LJ, United Kingdom

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Uxbridge, UB8 3NN, United Kingdom

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Related Publications (3)

• Robak T, Warzocha K, Govind Babu K, Kulyaba Y, Kuliczkowski K, Abdulkadyrov K, Loscertales J, Kryachok I, Kloczko J, Rekhtman G, Homenda W, Blonski JZ, McKeown A, Chang CN, Bal V, Lisby S, Gupta IV, Grosicki S. Health-related quality of life and patient-reported outcomes of ofatumumab plus fludarabine and cyclophosphamide versus fludarabine and cyclophosphamide in the COMPLEMENT 2 trial of patients with relapsed CLL. Leuk Lymphoma. 2017 Jul;58(7):1598-1606. doi: 10.1080/10428194.2016.1253837. Epub 2016 Nov 10.

  PMID: 27830957 DERIVED

• Robak T, Warzocha K, Govind Babu K, Kulyaba Y, Kuliczkowski K, Abdulkadyrov K, Loscertales J, Kryachok I, Kloczko J, Rekhtman G, Homenda W, Blonski JZ, McKeown A, Gorczyca MM, Carey JL, Chang CN, Lisby S, Gupta IV, Grosicki S. Ofatumumab plus fludarabine and cyclophosphamide in relapsed chronic lymphocytic leukemia: results from the COMPLEMENT 2 trial. Leuk Lymphoma. 2017 May;58(5):1084-1093. doi: 10.1080/10428194.2016.1233536. Epub 2016 Oct 12.

  PMID: 27731748 DERIVED

• Jewell RC, Laubscher K, Lewis E, Fang L, Gafoor Z, Carey J, McKeown A, West S, Wright O, Sedoti D, Dixon I, Hottenstein CS, Chan G. Assessment of the effect of ofatumumab on cardiac repolarization. J Clin Pharmacol. 2015 Jan;55(1):114-21. doi: 10.1002/jcph.376. Epub 2014 Aug 21.

  PMID: 25103870 DERIVED

MeSH Terms

Conditions

Leukemia, B-Cell; Recurrence; Neoplasms; Leukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Chronic Disease

Results Point of Contact

• Title: Clinical Disclosure Office
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  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: January 15, 2009
• First Posted: January 16, 2009
• Study Start: March 12, 2009
• Primary Completion: December 17, 2014
• Study Completion: October 25, 2017
• Last Updated: June 18, 2020
• Results First Posted: July 25, 2016

Record last verified: 2020-06

Locations

US (6); UA (11); IN (6); GB (13); TW (4); GR (4); ME (4); RO (4); ES (8); RU (7); NL (5); BU (7); BR (8); CA (8); DE (16); TH (3); PL (11); IT (10)