Study Stopped
Majority of patients (62%) had been treated with next line therapies, including new highly effective therapies confounding the interpretation of the OS results.
Ofatumumab + Chlorambucil vs Chlorambucil Monotherapy in Previously Untreated Patients With Chronic Lymphocytic Leukemia
COMPLEMENT 1
A Phase III, Open Label, Randomized, Multicenter Trial of Ofatumumab Added to Chlorambucil Versus Chlorambucil Monotherapy in Previously Untreated Patients With Chronic Lymphocytic Leukemia
1 other identifier
interventional
447
17 countries
154
Brief Summary
The purpose of this study was to evaluate the safety and efficacy of ofatumumab added to chlorambucil in patients with untreated Chronic Lymphocytic Leukemia.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Dec 2008
Longer than P75 for phase_3
154 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 5, 2008
CompletedFirst Posted
Study publicly available on registry
September 8, 2008
CompletedStudy Start
First participant enrolled
December 22, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 20, 2013
CompletedResults Posted
Study results publicly available
March 26, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
May 17, 2018
CompletedJune 25, 2019
June 1, 2019
4.2 years
September 5, 2008
November 14, 2013
June 5, 2019
Conditions
Keywords
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 (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 enlarged 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. Par. who were alive and had not progressed at the time of analysis or if a progression event or death occurred after extensive lost-to-follow-up time or if new anti-cancer therapy was started were censored at the date of the last visit with adequate assessment.
From randomization to the date of first documented disease progression or death due to any cause, whichever occured first, reported between day of first patient randomized up to about 49 months
Secondary Outcomes (24)
Number of Participants With the Best Overall Response (OR), as Assessed by the IRC
From randomization until the 259th PFS event occurred, up to about 49 months
Number of Participants Who Were Negative for Minimal Residual Disease (MRD)
From randomization until the 259th PFS event occurred (Median follow-up approximately 28.9 months)
Overall Survival
From randomization up to about 111 months
Time to Response, as Assessed by the IRC
From randomization uo to about 27 months
Duration of Response (DOR), as Assessed by the IRC
From randomization up to about 43 months
- +19 more secondary outcomes
Study Arms (2)
ofatumumab + chlorambucil
EXPERIMENTALofatumumab dose: cycle 1 300mg day 1 and 1000mg day 8, subsequent cycles: 1000mg at day 1 every 28 days; chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 treatment cycles
chlorambucil
ACTIVE COMPARATORchlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 cycles
Interventions
2mg tablets, chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 cycles
iv infusion; dose: cycle 1 300mg day 1 and 1000mg day 8, subsequent cycles: 1000mg at day 1 every 28 days;
Eligibility Criteria
You may qualify if:
- confirmed CLL diagnosis and active CLL requiring treatment
- considered inappropriate for fludarabine-based therapy
- not been treated for CLL before
- 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:
- prior CLL therapy
- abnormal/inadequate blood values, liver, and kidney function
- certain heart problems, active or chronic infections, serious significant diseases, active autoimmune hemolytic anemia (AIHA) requiring treatment, other current cancer or within last 5 years
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (154)
Novartis Investigative Site
Sedona, Arizona, 86336, United States
Novartis Investigative Site
Tucson, Arizona, 85704, United States
Novartis Investigative Site
Murrieta, California, 92562, United States
Novartis Investigative Site
Aurora, Colorado, 80012, United States
Novartis Investigative Site
Denver, Colorado, 80204, United States
Novartis Investigative Site
Boca Raton, Florida, 33486, United States
Novartis Investigative Site
New Port Richey, Florida, 34655, United States
Novartis Investigative Site
Ocala, Florida, 34471, United States
Novartis Investigative Site
Ocoee, Florida, 34761, United States
Novartis Investigative Site
Marietta, Georgia, 30060, United States
Novartis Investigative Site
Chicago, Illinois, 60612, United States
Novartis Investigative Site
Indianapolis, Indiana, 46227, United States
Novartis Investigative Site
Lee's Summit, Missouri, 64064, United States
Novartis Investigative Site
Raleigh, North Carolina, 27607, United States
Novartis Investigative Site
Abilene, Texas, 79606-5208, United States
Novartis Investigative Site
Arlington, Texas, 76014, United States
Novartis Investigative Site
Austin, Texas, 78731, United States
Novartis Investigative Site
Dallas, Texas, 75230, United States
Novartis Investigative Site
Dallas, Texas, 75231, United States
Novartis Investigative Site
Fort Worth, Texas, 76104, United States
Novartis Investigative Site
Midland, Texas, 79701, United States
Novartis Investigative Site
Odessa, Texas, 79761, United States
Novartis Investigative Site
San Antonio, Texas, 78217, United States
Novartis Investigative Site
San Antonio, Texas, 78229, United States
Novartis Investigative Site
Tyler, Texas, 75702, United States
Novartis Investigative Site
Waco, Texas, 76712, United States
Novartis Investigative Site
Webster, Texas, 77598-4420, United States
Novartis Investigative Site
Seattle, Washington, 98133, United States
Novartis Investigative Site
Vancouver, Washington, 98684, United States
Novartis Investigative Site
Yakima, Washington, 98902, United States
Novartis Investigative Site
Bruges, 8000, Belgium
Novartis Investigative Site
Brussels, 1200, Belgium
Novartis Investigative Site
Ghent, 9000, Belgium
Novartis Investigative Site
Haine-Saint-Paul, 7100, Belgium
Novartis Investigative Site
Leuven, 3000, Belgium
Novartis Investigative Site
Porto Alegre, Rio de Janeiro, 91350-200, Brazil
Novartis Investigative Site
São Paulo, São Paulo, 05403-000, Brazil
Novartis Investigative Site
São Paulo, São Paulo, 05651-901, Brazil
Novartis Investigative Site
Toronto, Ontario, M4N 3M5, Canada
Novartis Investigative Site
Montreal, Quebec, H3A1A1, Canada
Novartis Investigative Site
Sherbrooke, Quebec, J1H 5N4, Canada
Novartis Investigative Site
Brno, 625 00, Czechia
Novartis Investigative Site
Hradec Králové, Czechia
Novartis Investigative Site
Prague, 100 34, Czechia
Novartis Investigative Site
Créteil, 94010, France
Novartis Investigative Site
Pierre-Bénite, 69495, France
Novartis Investigative Site
Karlsruhe, Baden-Wurttemberg, 76137, Germany
Novartis Investigative Site
Mannheim, Baden-Wurttemberg, 68161, Germany
Novartis Investigative Site
Stuttgart, Baden-Wurttemberg, 70190, Germany
Novartis Investigative Site
Ulm, Baden-Wurttemberg, 89081, Germany
Novartis Investigative Site
Erlangen, Bavaria, 91052, Germany
Novartis Investigative Site
Munich, Bavaria, 81241, Germany
Novartis Investigative Site
Regensburg, Bavaria, 93049, Germany
Novartis Investigative Site
Würzburg, Bavaria, 97070, Germany
Novartis Investigative Site
Frankfurt am Main, Hesse, 65929, Germany
Novartis Investigative Site
Kassel, Hesse, 34119, Germany
Novartis Investigative Site
Hanover, Lower Saxony, 30625, Germany
Novartis Investigative Site
Lehrte, Lower Saxony, 31275, Germany
Novartis Investigative Site
Cologne, North Rhine-Westphalia, 50937, Germany
Novartis Investigative Site
Essen, North Rhine-Westphalia, 45122, Germany
Novartis Investigative Site
Moenchengladbach-Rheydt, North Rhine-Westphalia, 41239, Germany
Novartis Investigative Site
Münster, North Rhine-Westphalia, 48149, Germany
Novartis Investigative Site
Saarbrücken, Saarland, 66113, Germany
Novartis Investigative Site
Athens, 11 527, Greece
Novartis Investigative Site
Thessaloniki, 564 29, Greece
Novartis Investigative Site
Thessaloniki, 57010, Greece
Novartis Investigative Site
Ahmedabad, 380009, India
Novartis Investigative Site
Bangalore, 560029, India
Novartis Investigative Site
Mumbai, 400012, India
Novartis Investigative Site
Mumbai, 400014, India
Novartis Investigative Site
New Delhi, 110029, India
Novartis Investigative Site
Pune, 411001, India
Novartis Investigative Site
Cork, Ireland
Novartis Investigative Site
Dublin, 7, Ireland
Novartis Investigative Site
Galway, Ireland
Novartis Investigative Site
James Street, 8, Ireland
Novartis Investigative Site
Limerick, Ireland
Novartis Investigative Site
Tullamore, Ireland
Novartis Investigative Site
Waterford, Ireland
Novartis Investigative Site
Bari, Apulia, 70124, Italy
Novartis Investigative Site
Potenza, Basilicate, 85100, Italy
Novartis Investigative Site
Napoli, Campania, 80131, Italy
Novartis Investigative Site
Albano Laziale (Roma), Lazio, 00041, Italy
Novartis Investigative Site
Genoa, Liguria, 16132, Italy
Novartis Investigative Site
Brescia, Lombardy, 25123, Italy
Novartis Investigative Site
Milan, Lombardy, 20132, Italy
Novartis Investigative Site
Milan, Lombardy, 20133, Italy
Novartis Investigative Site
Milan, Lombardy, 20162, Italy
Novartis Investigative Site
Novara, Piedmont, 28100, Italy
Novartis Investigative Site
Palermo, Sicily, 90146, Italy
Novartis Investigative Site
Ascoli Piceno, The Marches, 63100, Italy
Novartis Investigative Site
Venezia - Mestre, Veneto, 30174, Italy
Novartis Investigative Site
Vicenza, Veneto, 36100, Italy
Novartis Investigative Site
Udine, 33100, Italy
Novartis Investigative Site
Amersfoort, 3818 ES, Netherlands
Novartis Investigative Site
Amsterdam, 1105 AZ, Netherlands
Novartis Investigative Site
Groningen, 9713 GZ, Netherlands
Novartis Investigative Site
Nijmegen, 6525 GA, Netherlands
Novartis Investigative Site
Rotterdam, 3015 CE, Netherlands
Novartis Investigative Site
Rotterdam, 3075 EA, Netherlands
Novartis Investigative Site
The Hague, 2545 CH, Netherlands
Novartis Investigative Site
Bialystok, 15-276, Poland
Novartis Investigative Site
Chorzów, 41-500, Poland
Novartis Investigative Site
Lodz, 93-510, Poland
Novartis Investigative Site
Słupsk, 76-200, Poland
Novartis Investigative Site
Warsaw, 02-776, Poland
Novartis Investigative Site
Wroclaw, 50-367, Poland
Novartis Investigative Site
Moscow, 115478, Russia
Novartis Investigative Site
Moscow, 125101, Russia
Novartis Investigative Site
Moscow, 125167, Russia
Novartis Investigative Site
Novosibirsk, 630051, Russia
Novartis Investigative Site
Saint Petersburg, 197 089, Russia
Novartis Investigative Site
St'Petersburg, 191024, Russia
Novartis Investigative Site
Barcelona, 08003, Spain
Novartis Investigative Site
Barcelona, 08025, Spain
Novartis Investigative Site
Hospitalet de Llobregat (Barcelona), 08907, Spain
Novartis Investigative Site
Madrid, 28006, Spain
Novartis Investigative Site
Madrid, 28041, Spain
Novartis Investigative Site
Madrid, 28046, Spain
Novartis Investigative Site
Salamanca, 37007, Spain
Novartis Investigative Site
Valencia, 46010, Spain
Novartis Investigative Site
Luleå, SE-971 80, Sweden
Novartis Investigative Site
Stockholm, SE-141 86, Sweden
Novartis Investigative Site
Uppsala, SE-751 85, Sweden
Novartis Investigative Site
Plymouth, Devon, PL6 8DH, United Kingdom
Novartis Investigative Site
Taunton, Somerset, TA1 5DA, United Kingdom
Novartis Investigative Site
Sunderland, Tyne, SR4 7TP, United Kingdom
Novartis Investigative Site
Bath, BA1 3NG, United Kingdom
Novartis Investigative Site
Belfast, BT9 7AB, United Kingdom
Novartis Investigative Site
Birmingham, B9 5SS, United Kingdom
Novartis Investigative Site
Bournemouth, BH7 7DW, United Kingdom
Novartis Investigative Site
Bradford, BD9 6RJ, United Kingdom
Novartis Investigative Site
Cambridge, CB2 0QQ, United Kingdom
Novartis Investigative Site
Canterbury, Kent, United Kingdom
Novartis Investigative Site
Carshalton, SM5 1AA, United Kingdom
Novartis Investigative Site
Cornwall, TR1 3LJ, United Kingdom
Novartis Investigative Site
Dudley, DY1 2HQ, United Kingdom
Novartis Investigative Site
Exeter, EX2 5DW, United Kingdom
Novartis Investigative Site
Glasgow, G12 OYN, United Kingdom
Novartis Investigative Site
Leeds, LS9 7TF, United Kingdom
Novartis Investigative Site
Liverpool, L7 8XP, United Kingdom
Novartis Investigative Site
London, EC1M 6BQ, United Kingdom
Novartis Investigative Site
London, SE5 9RS, United Kingdom
Novartis Investigative Site
Manchester, M13 9WL, United Kingdom
Novartis Investigative Site
Milton Keynes, MK6 5LD, United Kingdom
Novartis Investigative Site
Newcastle upon Tyne, NE7 7DN, United Kingdom
Novartis Investigative Site
Norwich, NR4 7UY, United Kingdom
Novartis Investigative Site
Oxford, OX3 7LJ, United Kingdom
Novartis Investigative Site
Peterborough, PE3 9GZ, United Kingdom
Novartis Investigative Site
Rhyl, Denbighshire, LL18 5UJ, United Kingdom
Novartis Investigative Site
Salford, M6 8HD, United Kingdom
Novartis Investigative Site
Stoke-on-Trent, ST4 6QG, United Kingdom
Novartis Investigative Site
Swindon, SN3 6BB, United Kingdom
Novartis Investigative Site
Uxbridge, UB8 3NN, United Kingdom
Related Publications (3)
Tausch E, Beck P, Schlenk RF, Jebaraj BJ, Dolnik A, Yosifov DY, Hillmen P, Offner F, Janssens A, Babu GK, Grosicki S, Mayer J, Panagiotidis P, McKeown A, Gupta IV, Skorupa A, Pallaud C, Bullinger L, Mertens D, Dohner H, Stilgenbauer S. Prognostic and predictive role of gene mutations in chronic lymphocytic leukemia: results from the pivotal phase III study COMPLEMENT1. Haematologica. 2020 Oct 1;105(10):2440-2447. doi: 10.3324/haematol.2019.229161.
PMID: 33054084DERIVEDHillmen P, Robak T, Janssens A, Babu KG, Kloczko J, Grosicki S, Doubek M, Panagiotidis P, Kimby E, Schuh A, Pettitt AR, Boyd T, Montillo M, Gupta IV, Wright O, Dixon I, Carey JL, Chang CN, Lisby S, McKeown A, Offner F; COMPLEMENT 1 Study Investigators. Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial. Lancet. 2015 May 9;385(9980):1873-83. doi: 10.1016/S0140-6736(15)60027-7. Epub 2015 Apr 14.
PMID: 25882396DERIVEDJewell 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: 25103870DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Disclosure Office
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
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
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 5, 2008
First Posted
September 8, 2008
Study Start
December 22, 2008
Primary Completion
March 20, 2013
Study Completion
May 17, 2018
Last Updated
June 25, 2019
Results First Posted
March 26, 2014
Record last verified: 2019-06
Data Sharing
- IPD Sharing
- Will share
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com