AzTrials
AzTrials

Leukaemia, Lymphocytic, ChronicPhase 3PROLONGNCT01039376

Ofatumumab Maintenance Treatment vs No Further Treatment in Relapsed CLL Responding to Induction Therapy

A Phase 3 study testing Ofatumumab and Observation in people with Leukaemia, Lymphocytic, Chronic, run by Novartis Pharmaceuticals at 203 sites in 25 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

The purpose of this study was to determine if maintenance therapy with ofatumumab would prolong remission in patients with CLL who have responded to second or third line treatment. This study would also evaluate the safety of ofatumumab maintenance compared to observation (the current standard of care). Read more about this study

Who is it for?
Any age
Conditions the study is for
Leukaemia, Lymphocytic, Chronic
What is being tested?
Ofatumumab and Observation
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
480 participants
Where
203 sitesin 25 countries
Study dates
6 May 2010to 26 Jun 2018
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Adults with documented diagnosis of CLL based on the modified IWCLL updated NCI-WG guidelines (Hallek, 2008)
  • At least PR according to the revised 2008 NCI-WG CLL criteria, within 3 months of the response assessment after the last dose of 2nd/3rd line treatment
  • The anti-leukemic treatment before study entry should have been at least 3 months or 3 cycles
  • ECOG Performance Status of 0-2
  • Signed written informed consent prior to performing any study-specific procedures

Who cannot join

  • Known primary or secondary fludarabine-refractory subjects, defined as treatment failure (failure to achieve a CR or PR) or disease progression within 6 months
  • Prior maintenance therapy
  • Known transformation of CLL (eg.Richter's transformation), prolymphocytic leukemia (PLL), or CNS involvement of CLL
  • Active Autoimmune hemolytic anemia (AIHA) requiring treatment except if in the opinion of the investigator and medical monitor it is thought not to affect the subject's safety, the conduct of the study or the interpretation of the data
  • Previous autologous or allogeneic stem cell transplantation
  • Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis B or C
Show all 16Show fewer
  • Other past or current malignancy (with the exception of basal cell carcinoma or the skin or in situ carcinoma of the cervix or breasts) unless the tumor was successfully treated with curative intent at least 2 years prior to trial entry except if in the opinion of the investigator and medical monitor it is thought not to affect the subject's safety, the conduct of the study or the interpretation of the data
  • Clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months prior to screening, congestive heart failure, and arrhythmia requiring therapy, with the exception of exta systoles or minor conduction abnormalities except if in the opinion of the investigator and medical monitor it is thought not to affect the subject's safety, the conduct of the study or the interpretation of the data
  • History of significant cerebrovascular disease or event with symptoms or sequelae
  • Significant concurrent, uncontrolled medical condition that in the opinion of the investigator or GSK medical monitor contraindicates participation in this study
  • Other anti-leukemic use of medications including glucocorticoids
  • Known HIV positive
  • Screening laboratory values: platelets <50 x 10x9/L, neutrophils<1.0 x 10x9/L, Creatinine > 1.5 X upper normal limit (unless normal creatinine clearance), total bilirubin >1.5 X upper normal limit, ALT >2.5 X upper normal limit (unless due to liver involvement of CLL), alkaline phosphase > 2.5 X upper normal limit
  • Known or suspected hypersensitivity to ofatumumab that in the opinion of the investigator or medical monitor contraindicates study participation
  • Subjects who have received treatment with any non-marketed drug substance or experimental therapy within 5-terminal half-lives or 4 weeks whichever is longer prior to first dose of study medication or currently participating in any other interventional clinical study
  • Lactating women, women with a positive pregnancy test at Visit 1 or women (of childbearing potential) as well as men with partners of childbearing potential, who are not willing to use adequate contraception from study start through one year following last ofatumumab dose. Adequate contraception is defined as abstinence, oral hormonal birth control, implants of levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, intrauterine device, and male partner sterilization if male partner is sole partner for that subject. For females in the USA, the use of a double barrier method is also considered adequate (condom or occlusive cap plus spermicidal agent).

Trial locations and contacts

203 sites in 25 countries.

203 sites in 25 countries

United States43 sites

  • Novartis Investigative Site

    Albuquerque, New Mexico, 87110

  • Novartis Investigative Site

    Albuquerque, New Mexico, 87131

  • Novartis Investigative Site

    Berkeley, California, 94704

  • Novartis Investigative Site

    Chapel Hill, North Carolina, 27599-7305

  • Novartis Investigative Site

    Chattanooga, Tennessee, 37421

  • Novartis Investigative Site

    Cumberland, Maryland, 21502

  • Novartis Investigative Site

    Detroit, Michigan, 48202

  • Novartis Investigative Site

    Durham, North Carolina, 27710

  • Novartis Investigative Site

    Gainesville, Florida, 32610

  • Novartis Investigative Site

    Gilbert, Arizona, 85234

  • Novartis Investigative Site

    Greenville, South Carolina, 29601

  • Novartis Investigative Site

    Hagerstown, Maryland, 21742

  • Novartis Investigative Site

    Hartford, Connecticut, 06105

  • Novartis Investigative Site

    Henderson, Nevada, 89014

  • Novartis Investigative Site

    Indianapolis, Indiana, 46202

  • Novartis Investigative Site

    Iowa City, Iowa, 52242

  • Novartis Investigative Site

    Jonesboro, Arkansas, 72401

  • Novartis Investigative Site

    Knoxville, Tennessee, 37916

  • Novartis Investigative Site

    La Verne, California, 91750

  • Novartis Investigative Site

    Lake Worth, Florida, 33461

  • Novartis Investigative Site

    Macon, Georgia, 31201

  • Novartis Investigative Site

    Memphis, Tennessee, 38120

  • Novartis Investigative Site

    Metairie, Louisiana, 70006

  • Novartis Investigative Site

    Mineola, New York, 11501

  • Novartis Investigative Site

    New Brunswick, New Jersey, 08901

  • Novartis Investigative Site

    Orem, Utah, 84058

  • Novartis Investigative Site

    Orlando, Florida, 32806

  • Novartis Investigative Site

    Pembroke Pines, Florida, 33028

  • Novartis Investigative Site

    Philadelphia, Pennsylvania, 19104

  • Novartis Investigative Site

    Post Falls, Idaho, 83854

  • Novartis Investigative Site

    Rochester, New York, 14621

  • Novartis Investigative Site

    Sacramento, California, 95815

  • Novartis Investigative Site

    Sacramento, California, 95816

  • Novartis Investigative Site

    Salt Lake City, Utah, 84106

  • Novartis Investigative Site

    San Pablo, California, 94806

  • Novartis Investigative Site

    Savannah, Georgia, 31405

  • Novartis Investigative Site

    Springfield, Missouri, 65807

  • Novartis Investigative Site

    St Louis, Missouri, 63110

  • Novartis Investigative Site

    Tucson, Arizona, 85710

  • Novartis Investigative Site

    Tucson, Arizona, 85715

  • Novartis Investigative Site

    West Palm Beach, Florida, 33401

  • Novartis Investigative Site

    Westwood, Kansas, 66205

  • Novartis Investigative Site

    Worcester, Massachusetts, 01655

Other trials in United States

Netherlands20 sites

  • Novartis Investigative Site

    's-Hertogenbosch, 5223 GZ

  • Novartis Investigative Site

    Amersfoort, 3813 TZ

  • Novartis Investigative Site

    Amsterdam, 1066 CX

  • Novartis Investigative Site

    Amsterdam, 1091 AC

  • Novartis Investigative Site

    Amsterdam, 1105 AZ

  • Novartis Investigative Site

    Blaricum, 1261 AN

  • Novartis Investigative Site

    Breda, 4819 EV

  • Novartis Investigative Site

    Deventer, 7416 SE

  • Novartis Investigative Site

    Dordrecht, 3318 AT

  • Novartis Investigative Site

    Enschede, 7511JX

  • Novartis Investigative Site

    Groningen, 9713 GZ

  • Novartis Investigative Site

    Hoofddorp, 2134 TM

  • Novartis Investigative Site

    Leiden, 2333 ZA

  • Novartis Investigative Site

    Maastricht, 6229 HX

  • Novartis Investigative Site

    Rotterdam, 3015 CE

  • Novartis Investigative Site

    Rotterdam, 3075 EA

  • Novartis Investigative Site

    Rotterdam, 3079 DZ

  • Novartis Investigative Site

    Sittard-geleen, 6162 BG

  • Novartis Investigative Site

    The Hague, 2545AA

  • Novartis Investigative Site

    Tilburg, 5022 GC

Other trials in Netherlands

France12 sites

  • Novartis Investigative Site

    Blois, 41016

  • Novartis Investigative Site

    Caen, 14076

  • Novartis Investigative Site

    Clermont-Ferrand, 63003

  • Novartis Investigative Site

    Dijon, 21000

  • Novartis Investigative Site

    Lille, 59037

  • Novartis Investigative Site

    Marseille, 13273

  • Novartis Investigative Site

    Mulhouse, 68070

  • Novartis Investigative Site

    Pessac, 33604

  • Novartis Investigative Site

    Saint-Pierre, 97448

  • Novartis Investigative Site

    Strasbourg, 67098

  • Novartis Investigative Site

    Toulouse, 31059

  • Novartis Investigative Site

    Vandœuvre-lès-Nancy, 54511

Other trials in France

Israel12 sites

  • Novartis Investigative Site

    Afula, 18101

  • Novartis Investigative Site

    Haifa, 31048

  • Novartis Investigative Site

    Haifa, 31096

  • Novartis Investigative Site

    Jerusalem, 91031

  • Novartis Investigative Site

    Jerusalem, 91120

  • Novartis Investigative Site

    Kfar Saba, 44281

  • Novartis Investigative Site

    Nahariya, 22100

  • Novartis Investigative Site

    Petah Tikva, 49100

  • Novartis Investigative Site

    Ramat Gan, 52621

  • Novartis Investigative Site

    Rehovot, 76100

  • Novartis Investigative Site

    Tel Aviv

  • Novartis Investigative Site

    Zrifin, 70300

Other trials in Israel

Poland9 sites

  • Novartis Investigative Site

    Bialystok, 15-276

  • Novartis Investigative Site

    Chorzów, 41-500

  • Novartis Investigative Site

    Słupsk, 76-200

  • Novartis Investigative Site

    Szczecin, 71-252

  • Novartis Investigative Site

    Warsaw, 02-097

  • Novartis Investigative Site

    Warsaw, 02-776

  • Novartis Investigative Site

    Warsaw

  • Novartis Investigative Site

    Wroclaw, 50-367

  • Novartis Investigative Site

    Wroclaw, 53-439

Other trials in Poland

Russia9 sites

  • Novartis Investigative Site

    Kazan', 420029

  • Novartis Investigative Site

    Moscow, 115478

  • Novartis Investigative Site

    Moscow, 125167

  • Novartis Investigative Site

    Novosibirsk, 630087

  • Novartis Investigative Site

    Penza, 440071

  • Novartis Investigative Site

    Saint Petersburg, 197 089

  • Novartis Investigative Site

    St'Petersburg, 191024

  • Novartis Investigative Site

    St'Petersburg, 197341

  • Novartis Investigative Site

    Volgograd, 400138

Other trials in Russia

Ukraine9 sites

  • Novartis Investigative Site

    Cherkasy, 18009

  • Novartis Investigative Site

    Dnipropetrovsk, 49102

  • Novartis Investigative Site

    Kharkiv, 61070

  • Novartis Investigative Site

    Khmelnytskyi, 29000

  • Novartis Investigative Site

    Kyiv, 03022

  • Novartis Investigative Site

    Lviv, 79044

  • Novartis Investigative Site

    Makiivka, 86132

  • Novartis Investigative Site

    Vinnitsa, 21018

  • Novartis Investigative Site

    Zhytomyr, 10002

Other trials in Ukraine

Belgium8 sites

  • Novartis Investigative Site

    Antwerp, 2020

  • Novartis Investigative Site

    Antwerp, 2060

  • Novartis Investigative Site

    Bruges, 8000

  • Novartis Investigative Site

    Brussels, 1090

  • Novartis Investigative Site

    Ghent, 9000

  • Novartis Investigative Site

    Hasselt, 3500

  • Novartis Investigative Site

    Roeselare, 8800

  • Novartis Investigative Site

    Wilrijk, 2610

Other trials in Belgium

Canada7 sites

  • Novartis Investigative Site

    Calgary, Alberta, T2N 4N2

  • Novartis Investigative Site

    Kitchener, Ontario, N2G 1G3

  • Novartis Investigative Site

    Montreal, Quebec, H2L 4M1

  • Novartis Investigative Site

    Montreal, Quebec, H3A1A1

  • Novartis Investigative Site

    Saskatoon, Saskatchewan, S7N 4H4

  • Novartis Investigative Site

    Sherbrooke, Quebec, J1H 5N4

  • Novartis Investigative Site

    Toronto, Ontario, M4N 3M5

Other trials in Canada

Spain7 sites

  • Novartis Investigative Site

    Hospitalet de Llobregat (Barcelona), 08907

  • Novartis Investigative Site

    Madrid, 28031

  • Novartis Investigative Site

    Madrid, 28040

  • Novartis Investigative Site

    Salamanca, 37007

  • Novartis Investigative Site

    Seville, 41013

  • Novartis Investigative Site

    Toledo, 45004

  • Novartis Investigative Site

    Zaragoza, 50009

Other trials in Spain

Argentina6 sites

  • Novartis Investigative Site

    Buenos Aires, 1114

  • Novartis Investigative Site

    Capital Federal, Buenos Aires, C1426ANZ

  • Novartis Investigative Site

    Ciudad Autonoma de Buenos Aires, Buenos Aires, C1431FWO

  • Novartis Investigative Site

    Derqui, Pilar, Buenos Aires, B1629AHJ

  • Novartis Investigative Site

    La Plata, Buenos Aires, B1900AXI

  • Novartis Investigative Site

    Rosario, Santa Fe Province, S2000KZE

Other trials in Argentina

Brazil6 sites

  • Novartis Investigative Site

    Barretos, São Paulo, 14784-400

  • Novartis Investigative Site

    Goiania - GO, Goiás, 74605-020

  • Novartis Investigative Site

    Porto Alegre, Rio Grande do Sul, 90610000

  • Novartis Investigative Site

    Salvador, Estado de Bahia, 41253-190

  • Novartis Investigative Site

    São Paulo, São Paulo, 01221-001

  • Novartis Investigative Site

    São Paulo, São Paulo, 05403-000

Other trials in Brazil

Italy6 sites

  • Novartis Investigative Site

    Modena, Emilia-Romagna, 41124

  • Novartis Investigative Site

    Novara, Piedmont, 28100

  • Novartis Investigative Site

    Piacenza, Emilia-Romagna, 29100

  • Novartis Investigative Site

    Pisa, Tuscany, 56100

  • Novartis Investigative Site

    Rome, Lazio, 00144

  • Novartis Investigative Site

    Turin, Piedmont, 10126

Other trials in Italy

Sweden6 sites

  • Novartis Investigative Site

    Gothenburg, SE-413 45

  • Novartis Investigative Site

    Linköping, SE-581 85

  • Novartis Investigative Site

    Luleå, SE-971 80

  • Novartis Investigative Site

    Örebro, SE-701 85

  • Novartis Investigative Site

    Stockholm, SE 171 76

  • Novartis Investigative Site

    Uppsala, SE-751 85

Other trials in Sweden

Australia5 sites

  • Novartis Investigative Site

    Clayton, Victoria, 3168

  • Novartis Investigative Site

    Darlinghurst, New South Wales, 2010

  • Novartis Investigative Site

    East Melbourne, Victoria, 3002

  • Novartis Investigative Site

    Parkville, Victoria, 3050

  • Novartis Investigative Site

    Randwick, New South Wales, 2031

Other trials in Australia

Czechia5 sites

  • Novartis Investigative Site

    Brno, 625 00

  • Novartis Investigative Site

    Hradec Králové

  • Novartis Investigative Site

    Olomouc, 775 20

  • Novartis Investigative Site

    Pelhřimov, 393 38

  • Novartis Investigative Site

    Prague, 100 34

Other trials in Czechia

Finland5 sites

  • Novartis Investigative Site

    Helsinki, 00029

  • Novartis Investigative Site

    Jyväskylä, 40620

  • Novartis Investigative Site

    Pori, 28500

  • Novartis Investigative Site

    Tampere, 33520

  • Novartis Investigative Site

    Turku, 20520

Other trials in Finland

Greece5 sites

  • Novartis Investigative Site

    Athens, 11 527

  • Novartis Investigative Site

    Athens, 115 27

  • Novartis Investigative Site

    Piraeus, 18537

  • Novartis Investigative Site

    Thessaloniki, 564 29

  • Novartis Investigative Site

    Thessaloniki, 57010

Other trials in Greece

South Korea5 sites

  • Novartis Investigative Site

    Seoul, 03080

  • Novartis Investigative Site

    Seoul, 03722

  • Novartis Investigative Site

    Seoul, 05505

  • Novartis Investigative Site

    Seoul, 06351

  • Novartis Investigative Site

    Seoul, 06591

Other trials in South Korea

Turkey (Türkiye)5 sites

  • Novartis Investigative Site

    Ankara, 06590

  • Novartis Investigative Site

    Ankara

  • Novartis Investigative Site

    Istanbul, 34093

  • Novartis Investigative Site

    Izmir, 35340

  • Novartis Investigative Site

    Izmir

Other trials in Turkey (Türkiye)

Hungary4 sites

  • Novartis Investigative Site

    Budapest, 1097

  • Novartis Investigative Site

    Debrecen, 4012

  • Novartis Investigative Site

    Kecskemét, 6000

  • Novartis Investigative Site

    Szeged, 6725

Other trials in Hungary

India4 sites

  • Novartis Investigative Site

    Ahmedabad, 380009

  • Novartis Investigative Site

    Mumbai, 400 012

  • Novartis Investigative Site

    Mumbai, 400014

  • Novartis Investigative Site

    Pune, 411001

Other trials in India

Denmark3 sites

  • Novartis Investigative Site

    Copenhagen, 2100

  • Novartis Investigative Site

    Herlev, 2730

  • Novartis Investigative Site

    Roskilde, 4000

Other trials in Denmark

Norway1 site

  • Novartis Investigative Site

    Oslo, 0027

Other trials in Norway

Puerto Rico1 site

  • Novartis Investigative Site

    San Juan, 00918

Other trials in Puerto Rico

About this study

Official title: A Phase III, Open Label, Randomized, Multicenter Trial of Ofatumumab Maintenance Treatment Versus no Further Treatment in Subjects With Relapsed Chronic Lymphocytic Leukemia (CLL) Who Have Responded to Induction Therapy

The purpose of this study was to determine if maintenance therapy with ofatumumab would prolong remission in patients with CLL who have responded to second or third line treatment. This study would also evaluate the safety of ofatumumab maintenance compared to observation (the current standard of care). This study was co-developed with the HOVON and NORDIC CLL group and would be conducted as a collaborative effort with GSK.

Read the detailed description

The study met its primary objective at the protocol defined interim analysis (data cut-off 19-Jun-2014). The protocol-defined final analysis of the primary endpoint was performed when 280 PFS events were reached (data cut-off 20-Feb-2017).

Being tested
Ofatumumab, Observation
Keywords
maintenance therapy, anti-CD20 monoclonal antibody, ofatumumab
Medical subject headings
Leukemia, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OfatumumabBiological

    Ofatumumab for maintenance therapy as IV infusions every 8 weeks . The first dose was 300 mg followed 1 week later by 1000 mg and 1000 mg every 8 weeks thereafter for up to 2 years.

  • ObservationOther

    Observation/Safety Evaluation

Study groups in NCT01039376
Study groupRoleWhat they receive
ARM A: OfatumumabExperimental300 mg IV Week 1 followed by 1000 mg IV Week 2 1000 mg IV (a dose every 8 weeks for up to 2 years following the first 1000 mg dose)
Receives: Biological: Ofatumumab
ARM B: Observation and assessments as per Arm AOtherDisease status assessments to determine subject response or progression performed approximately every 8 weeks for up to 2 years for both arms according to IWCLL criteria
Receives: Other: Observation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival, as Assessed by the Investigator

    Progression-free survival is defined as the time from randomization to the date of disease progression (PD) or death due to any cause. PD was determined by the investigator according to the definitions of response in the International Workshop for Chronic Lymphocytic Leukemia (IWCLL) updated National Cancer Institute-Sponsored Working Group (NCI-WG) guidelines. According to the guidelines, PD is characterized by at least one of the following: lymphadenopathy (appearance of any new lesion such as enlarged lymph nodes (>1.5 centimeter [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 leukemia.

    Measured: From randomization until progression or death (up to 79 months)

  2. Progression-free Survival, as Assessed by the Independent Review Committee (IRC)

    Progression-free survival is defined as the time from randomization to the date of disease progression (PD) or death due to any cause. PD was determined by the IRC according to the definitions of response in the International Workshop for Chronic Lymphocytic Leukemia (IWCLL) updated National Cancer Institute-Sponsored Working Group (NCI-WG) guidelines. According to the guidelines, PD is characterized by at least one of the following: lymphadenopathy (appearance of any new lesion such as enlarged lymph nodes (>1.5 centimeter [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 leukemia.

    Measured: From randomization until progression or death (up to 79 months)

Secondary outcomes (25)

  1. Overall Survival

    Overall survival is defined as time from randomization to date of death.

    Measured: From randomization until death (up to 88 months)

  2. Number of Participants With Improvement in Response From Baseline

    Improvement in response was assessed by calculating the percentage of participants who changed from partial response (PR) at Baseline to complete response during the study.

    Measured: From Baseline until the end of the study (up to 88 months)

  3. Time to Next Therapy

    Time to next therapy is defined as the time from randomization to the date of receiving the next CLL treatment.

    Measured: From randomization until the end of the study (up to 88 months)

  4. Progression-free Survival After Next-line Therapy

    Progression-free survival after next-line therapy is defined as the time from randomization until progression or death following the next-line therapy and counted as events deaths prior to next-line therapy. Participants who received next-line therapy and who did not have progression or death after next-line therapy were censored at their last date of contact. Participant who died prior to next-line therapy, was counted as an event.

    Measured: From randomization until progression or death (up to 88 months)

  5. Time to Progression After Next-line Therapy

    Time to progression after next-line therapy is defined as the time from progression following randomization until progression or death following next-line therapy and counted as events deaths prior to next-line therapy. Participants who received next-line therapy with a PD prior to receiving next line therapy and who did not had progression or death after next-line therapy were censored at their last date of contact. If a participant died prior to next-line therapy, this was counted as an event.

    Measured: From randomization until progression or death (up to 88 months)

  6. Change From Baseline (BL) in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Chronic Lymphocytic Leukaemia 16 Item Module (EORTC QLQ-CLL 16)

    The EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of health-related quality of life (HRQoL) important in CLL. There are 4 multi-item scales - fatigue (2 items), treatment side effects ([TSE], 4 items), disease symptoms (disease effects scale [DES], 4 items), and infection (4 items) - and single-item scales (social activities [Social Problems (SP) Scale] and future health worries [Future Health (FH) Scale]). These are measured on a four-point Likert scale, where 1 = not at all and 4 = very much. These scores are transformed to give a rating from 0 - 100, where 0 = no symptoms or problems and 100 = severe symptoms or problems. Changes from Baseline were analyzed by a mixed model-repeated measures analysis of covariance (ANCOVA).

    Measured: From randomization until the end of the study (up to 47 months)

  7. Change From Baseline in the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Score

    The EORTC QLQ-C30 is a self-reported, 30-item cancer-specific instrument that assesses 15 domains: physical functioning (5 items), role functioning (2 items), emotional functioning (4 items), cognitive functioning (2 items), social functioning (2 items), pain (2 items), fatigue (3 items), nausea and vomiting (2 items), five single-item symptom scores (insomnia, loss of appetite, constipation, diarrhea, and dyspnea), a single item asking about financial difficulties, and global health status/quality of life (QOF) consisting of 2 items. Functional and symptoms scales were measured on a four-point Likert scale, where 1 = not at all and 4 = very much, whereas global health status or QOF was assessed using a 7-item Likert scale, ranging from "poor" (worse quality of life) to "excellent" (better quality of life). Changes from Baseline were analyzed by mixed model-repeated measures ANCOVA.

    Measured: From randomization until the end of the study (up to 47 months)

  8. Change From Baseline in the Quality of Life Status as Assessed by the EuroQol-5D (EQ-5D) Scale

    EQ-5D is comprised of a 5-item health status measure and a visual analogue scale (VAS) and is used to generate two scores: the utility score and the thermometer score. The utility score measures mobility, self-care, usual activities, pain, discomfort, and anxiety/depression. Responses to each of the 5 health states are measured on a 3-point scale (level 1 = no problem; level 2 = some or moderate problem[s] and level 3 = unable, or extreme problems). Responses are typically converted into health utilities or valuations on a scale ranging from 0 (worst health) to 1 (perfect health). The thermometer score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). Changes from Baseline were analyzed by mixed model-repeated measures ANCOVA. A negative adjusted mean change from Baseline represents a worsening of quality of life.

    Measured: From screening until the end of the study (up to 47 months)

  9. Number of Participants With an Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status at the Indicated Time Points

    Improvement is defined as a decrease from Baseline by at least one step on the ECOG performance status scale (improvement categorized as yes or no). Improvement in ECOG performance status was measured.

    Measured: From randomization until the end of the study (up to 88 months)

  10. Number of Participants With the Indicated Constitutional or B-symptoms at the Indicated Time Points

    Participants with the indicated constitutional or B-symptoms (night sweats [without signs of infection]; unintentional weight loss >= 10% within the previous 6 months; recurrent, unexplained fever of > 38 degrees celcius or 100.5 degrees fahrenheit for 2 weeks; and extreme fatigue) were presented. The proportion of participants with no night sweats, no weight loss, no fever and no extreme fatigue were summarized.

    Measured: From Screening until the end of the study (up to 88 months)

  11. Number of Participants With Grade 3 and Above Adverse Event of Infection

    Participants with Grade 3, Grade 4 and Grade 5 adverse event of infection are presented. Adverse events were graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) grade, version 4.0 (1=mild; 2=moderate; 3=severe; 4=life-threatening/disabling; 5=death).

    Measured: From first dose of study medication until 60 days after the last dose of study medication or until the last observation at Visit 14 (up to 26 months)

  12. Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)

    An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.

    Measured: From first dose of study medication until 60 days after the last dose of study medication or until the last observation at Visit 14 for AEs (up to 26 months) and until end of study for SAEs (88 months)

  13. Number of Participants With a Grade 3 or Grade 4 Myelosuppression (Anemia, Neutropenia, or Thrombocytopenia) at Indicated Time Points

    Myelosuppression is defined as the decrease in the ability of the bone marrow to produce blood cells. Number of participants who reported myelosuppression (anemia [low hemoglobin count], neutropenia [low neutrophil count], and thrombocytopenia [low platelet count]) are presented. AEs were graded according to NCI common terminology criteria for adverse events (CTCAE) grade, version 4.0 (1, mild; 2, moderate; 3, severe; 4, life-threatening/disabling; 5, death).

    Measured: From first dose of study medication until 60 days after the last dose of study medication or until the last observation at Visit 14 for AEs (up to 26 months) and until the end of the study for SAEs (88 months)

  14. Number of Participants Who Received at Least One Transfusion During the Study

    Participants who received at least one transfusion (any blood products or blood supportive care product) during the study are presented.

    Measured: From randomization until the end of the study (up to 88 months)

  15. Number of Participants Diagnosed With Autoimmune Hemolytic Anemia (AIHA)

    AIHA is a disease where the body's immune system fails to recognize red blood cells as "self" and begins destroying these red blood cells. The number of participants diagnosed with AIHA are presented.

    Measured: From randomization until the end of the study (up to 88 months)

  16. Number of Participants With a Positive Anti-ofatumumab Antibody (Human Anti-human Antibody; HAHA) Result

    All serum samples for analysis of HAHA were first tested in a screening step; positive samples from the screening were further evaluated in a confirmation test. The confirmed positive samples were reported as HAHA positive and further evaluated in the titration test to obtain a titer of HAHA. A confirmed positive result at any time point means the participant is positive for HAHA.Results are reported as the number of participants positive for HAHA.

    Measured: Pre-dose (Visit 1), Months 7, 13, 19, and 25 during treatment and at 3 and 6 months after last ofatumumab dose (up to 30 months)

  17. Mean Change From Baseline in the Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM at Indicated Time Points

    Immunoglobulins, or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Low levels indicate immuno-suppression. IgA, IgG, and IgM were measured in the blood samples of the participants. Baseline IgA, IgG, and IgM values are the last pre-dose assessment values performed on Cycle 1 Day 1. Change from Baseline was calculated as the post-baseline value minus the Baseline value.

    Measured: Baseline, every six months during treatment, and after last treatment visit and/or upon relapse (up to 88 months)

  18. Number of Participants Who Were Positive and Negative for Minimal Residual Disease (MRD) at Any Visit

    MRD refers to small number of leukemic cells that remain in the participant during treatment or after treatment at the time the participant achieved a confirmed complete remission. Number of participants who were positive and negative for minimal residual disease (MRD) at any visit is presented.

    Measured: From randomization until the end of the study (up to 88 months)

  19. Change From Baseline in Cluster of Differentiation (CD) CD5+CD19+ and CD5-CD19+ Cell Counts at the Indicated Time Points

    CD5+CD19+ cells were counted by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus. Baseline CD5+CD19+ and CD5-CD19+ cell count value is the last pre-dose assessment values performed on Cycle 1 Day 1. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

    Measured: Baseline and every two months from Month 3 until Month 25 and at every followup (up to 88 months)

  20. Summary of Covariates to Compute Cox Proportional Hazards Regression Model for Relationship Between Investigator Assessed Progression-free Survival and the Indicated Prognostic Markers

    Blood samples were collected for the assessment of the following prognostic markers at Baseline (BL) and upon relapse: immunoglobulin heavy chain variable region (IgVH) mutational status; VH3-21 usage; Cytogenetics (by fluorescent in situ hybridization [FISH]) including 6q-, 11q-, +12q, 17p-, 13q- deletions; beta 2 microglobulin. Cox-regression model was used to explore the relationship between progression-free survival and the following explanatory variables: treatment group, cytogenetics (analyzed by FISH) at BL, IgVH mutational status at BL, beta 2 microglobulin at BL, BL CD20 and BL complement level. For each covariate, a hazard ratio <1 indicates a lower risk on the first effect tested compared with the other effects tested. Cytogenetics Group (based on >=20%)=CY G.

    Measured: From Baseline until the end of the study (up to 79 months)

  21. Cmax and Ctrough of Ofatumumab

    Blood samples were collected to assess the plasma concentration of ofatumumab. Maximum concentration (Cmax) and observed drug concentration prior to the next dose (Ctrough) were determined. Blood samples were collected at pre-dose and 0.5 hours after the end of the infusion at treatment on Month 1 Week 1 (Day 1), Month 1 Week 2 (Day 8), and at every second infusion.

    Measured: Day 1 of Month 1 (Cycle 1 Week 1); Day 8 of Month 1 (Cycle 1 Week 2); and Month 7 (Cycle 4)

  22. Total Plasma Clearance (CL) of Ofatumumab

    Plasma clearance is defined as the plasma volume that is cleared of drug per unit of time.

    Measured: Day 1 of Month 1 (Cycle 1 Week 1); Day 8 of Month 1 (Cycle 1 Week 2); and Month 7 (Cycle 4)

  23. AUC(0-tau) of Ofatumumab

    Area under the concentration time curve over the dosing interval (AUC[0-tau]) is a measure of the drug exposure over time.

    Measured: Day 1 of Month 1 (Cycle 1 Week 1); Day 8 of Month 1 (Cycle 1 Week 2); and Month 7 (Cycle 4)

  24. Vss of Ofatumumab

    Volume of distribution at steady state (Vss) is defined as the apparent volume of distribution of a drug between plasma and the rest of the body at steady state. Data from all time points collected were used to calculate one Vss value for each individual.

    Measured: Day 1 Month 1 ( Cycle 1) through Month 7 ( Cycle 4)

  25. Plasma Half-life (t1/2) of Ofatumumab

    The terminal half life (t1/2) of ofatumumab is defined as the time required for the plasma concentration of ofatumumab to reach half of its original value.

    Measured: Day 1 of Month 1 (Cycle 1 Week 1); Day 8 of Month 1 (Cycle 1 Week 2); and Month 7 (Cycle 4)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Dec 2009 (estimated)
  2. Study start6 May 2010
  3. Primary completion20 Feb 2017
  4. Study completion26 Jun 2018

Why it stopped: Sponsor decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Masking
None (open label)
Enrolment
480 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01039376
Sponsor's protocol ID
112517
Other IDs
COMB157C2301
Acronym
PROLONG
Status last verified
Jul 2019
First submitted
23 Dec 2009
Last updated
30 Jul 2019
Data monitoring committee
Yes
Individual data sharing
Yes: 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

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ofatumumab and Observation in people with Leukaemia, Lymphocytic, Chronic, run by Novartis Pharmaceuticals at 203 sites in 25 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 30 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 203 sites in United States, Netherlands, France, Israel, Poland and 20 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Apr 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival, as Assessed by the Investigator (time frame: From randomization until progression or death (up to 79 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01039376.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2019.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in