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

NCT01039376 | Terminated Phase 3 Results DMC

• 2 other identifiers: 112517COMB157C2301
• Study Type: interventional
• Target: 480
• Locations: 25 countries
• Sites: 203

Brief 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). This study was co-developed with the HOVON and NORDIC CLL group and would be conducted as a collaborative effort with GSK.

Conditions

Leukaemia, Lymphocytic, Chronic

Keywords

maintenance therapy; anti-CD20 monoclonal antibody; ofatumumab

Outcome Measures

Primary Outcomes (2)

• 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.

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

• 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.

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

Secondary Outcomes (25)

• Overall Survival

  From randomization until death (up to 88 months)

• Number of Participants With Improvement in Response From Baseline

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

• Time to Next Therapy

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

• Progression-free Survival After Next-line Therapy

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

• Time to Progression After Next-line Therapy

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

Study Arms (2)

ARM A: Ofatumumab

EXPERIMENTAL

300 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)

Biological: Ofatumumab

ARM B: Observation and assessments as per Arm A

OTHER

Disease 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

Other: Observation

Interventions

Ofatumumab BIOLOGICAL

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.

ARM A: Ofatumumab

Observation OTHER

Observation/Safety Evaluation

ARM B: Observation and assessments as per Arm A

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (203)

Novartis Investigative Site

Gilbert, Arizona, 85234, United States

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Tucson, Arizona, 85710, United States

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Tucson, Arizona, 85715, United States

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Jonesboro, Arkansas, 72401, United States

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Berkeley, California, 94704, United States

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La Verne, California, 91750, United States

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Sacramento, California, 95815, United States

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Sacramento, California, 95816, United States

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San Pablo, California, 94806, United States

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Hartford, Connecticut, 06105, United States

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Gainesville, Florida, 32610, United States

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Lake Worth, Florida, 33461, United States

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Orlando, Florida, 32806, United States

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Pembroke Pines, Florida, 33028, United States

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West Palm Beach, Florida, 33401, United States

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Macon, Georgia, 31201, United States

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Savannah, Georgia, 31405, United States

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Post Falls, Idaho, 83854, United States

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Indianapolis, Indiana, 46202, United States

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Iowa City, Iowa, 52242, United States

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Westwood, Kansas, 66205, United States

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Metairie, Louisiana, 70006, United States

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Cumberland, Maryland, 21502, United States

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Hagerstown, Maryland, 21742, United States

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Worcester, Massachusetts, 01655, United States

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Detroit, Michigan, 48202, United States

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Springfield, Missouri, 65807, United States

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St Louis, Missouri, 63110, United States

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Henderson, Nevada, 89014, United States

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New Brunswick, New Jersey, 08901, United States

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Albuquerque, New Mexico, 87110, United States

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Albuquerque, New Mexico, 87131, United States

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Mineola, New York, 11501, United States

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Rochester, New York, 14621, United States

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

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Durham, North Carolina, 27710, United States

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Philadelphia, Pennsylvania, 19104, United States

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Greenville, South Carolina, 29601, United States

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Chattanooga, Tennessee, 37421, United States

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Knoxville, Tennessee, 37916, United States

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Memphis, Tennessee, 38120, United States

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Orem, Utah, 84058, United States

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Salt Lake City, Utah, 84106, United States

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Capital Federal, Buenos Aires, C1426ANZ, Argentina

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

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Derqui, Pilar, Buenos Aires, B1629AHJ, Argentina

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La Plata, Buenos Aires, B1900AXI, Argentina

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Rosario, Santa Fe Province, S2000KZE, Argentina

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Buenos Aires, 1114, Argentina

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Darlinghurst, New South Wales, 2010, Australia

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Randwick, New South Wales, 2031, Australia

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Clayton, Victoria, 3168, Australia

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East Melbourne, Victoria, 3002, Australia

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Parkville, Victoria, 3050, Australia

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Antwerp, 2020, Belgium

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Antwerp, 2060, Belgium

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Bruges, 8000, Belgium

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Brussels, 1090, Belgium

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Ghent, 9000, Belgium

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Hasselt, 3500, Belgium

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Roeselare, 8800, Belgium

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Wilrijk, 2610, Belgium

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Salvador, Estado de Bahia, 41253-190, Brazil

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Goiania - GO, Goiás, 74605-020, Brazil

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Porto Alegre, Rio Grande do Sul, 90610000, Brazil

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Barretos, São Paulo, 14784-400, Brazil

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São Paulo, São Paulo, 01221-001, Brazil

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São Paulo, São Paulo, 05403-000, Brazil

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Calgary, Alberta, T2N 4N2, Canada

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Kitchener, Ontario, N2G 1G3, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Montreal, Quebec, H2L 4M1, Canada

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Montreal, Quebec, H3A1A1, Canada

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Sherbrooke, Quebec, J1H 5N4, Canada

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Saskatoon, Saskatchewan, S7N 4H4, Canada

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Brno, 625 00, Czechia

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Hradec Králové, Czechia

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Olomouc, 775 20, Czechia

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Pelhřimov, 393 38, Czechia

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Prague, 100 34, Czechia

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Copenhagen, 2100, Denmark

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Herlev, 2730, Denmark

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Roskilde, 4000, Denmark

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Helsinki, 00029, Finland

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Jyväskylä, 40620, Finland

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Pori, 28500, Finland

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Tampere, 33520, Finland

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Turku, 20520, Finland

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Blois, 41016, France

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Caen, 14076, France

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Clermont-Ferrand, 63003, France

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Dijon, 21000, France

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Lille, 59037, France

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Marseille, 13273, France

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Mulhouse, 68070, France

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Pessac, 33604, France

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Saint-Pierre, 97448, France

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Strasbourg, 67098, France

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Toulouse, 31059, France

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Vandœuvre-lès-Nancy, 54511, France

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Athens, 11 527, Greece

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Athens, 115 27, Greece

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Piraeus, 18537, Greece

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Thessaloniki, 564 29, Greece

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Thessaloniki, 57010, Greece

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Budapest, 1097, Hungary

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Debrecen, 4012, Hungary

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Kecskemét, 6000, Hungary

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Szeged, 6725, Hungary

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Ahmedabad, 380009, India

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Mumbai, 400 012, India

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Mumbai, 400014, India

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Pune, 411001, India

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Afula, 18101, Israel

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Haifa, 31048, Israel

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Haifa, 31096, Israel

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Jerusalem, 91031, Israel

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Jerusalem, 91120, Israel

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Kfar Saba, 44281, Israel

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Nahariya, 22100, Israel

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Petah Tikva, 49100, Israel

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Ramat Gan, 52621, Israel

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Rehovot, 76100, Israel

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Tel Aviv, Israel

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Zrifin, 70300, Israel

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Modena, Emilia-Romagna, 41124, Italy

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Piacenza, Emilia-Romagna, 29100, Italy

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Rome, Lazio, 00144, Italy

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Novara, Piedmont, 28100, Italy

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Turin, Piedmont, 10126, Italy

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Pisa, Tuscany, 56100, Italy

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's-Hertogenbosch, 5223 GZ, Netherlands

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Amersfoort, 3813 TZ, Netherlands

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Amsterdam, 1066 CX, Netherlands

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Amsterdam, 1091 AC, Netherlands

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Amsterdam, 1105 AZ, Netherlands

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Blaricum, 1261 AN, Netherlands

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Breda, 4819 EV, Netherlands

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Deventer, 7416 SE, Netherlands

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Dordrecht, 3318 AT, Netherlands

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Enschede, 7511JX, Netherlands

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Groningen, 9713 GZ, Netherlands

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Hoofddorp, 2134 TM, Netherlands

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Leiden, 2333 ZA, Netherlands

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Maastricht, 6229 HX, Netherlands

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Rotterdam, 3015 CE, Netherlands

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Rotterdam, 3075 EA, Netherlands

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Rotterdam, 3079 DZ, Netherlands

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Sittard-geleen, 6162 BG, Netherlands

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The Hague, 2545AA, Netherlands

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Tilburg, 5022 GC, Netherlands

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Oslo, 0027, Norway

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Bialystok, 15-276, Poland

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Chorzów, 41-500, Poland

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Szczecin, 71-252, Poland

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Słupsk, 76-200, Poland

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Warsaw, 02-097, Poland

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Warsaw, 02-776, Poland

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Warsaw, Poland

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Wroclaw, 50-367, Poland

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Wroclaw, 53-439, Poland

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San Juan, 00918, Puerto Rico

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Kazan', 420029, Russia

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Moscow, 115478, Russia

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Moscow, 125167, Russia

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Novosibirsk, 630087, Russia

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Penza, 440071, Russia

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Saint Petersburg, 197 089, Russia

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St'Petersburg, 191024, Russia

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St'Petersburg, 197341, Russia

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Volgograd, 400138, Russia

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Seoul, 03080, South Korea

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Seoul, 03722, South Korea

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Seoul, 05505, South Korea

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Seoul, 06351, South Korea

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Seoul, 06591, South Korea

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Hospitalet de Llobregat (Barcelona), 08907, Spain

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Madrid, 28031, Spain

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Madrid, 28040, Spain

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Salamanca, 37007, Spain

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Seville, 41013, Spain

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Toledo, 45004, Spain

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Zaragoza, 50009, Spain

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Gothenburg, SE-413 45, Sweden

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Linköping, SE-581 85, Sweden

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Luleå, SE-971 80, Sweden

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Örebro, SE-701 85, Sweden

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Stockholm, SE 171 76, Sweden

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Uppsala, SE-751 85, Sweden

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Ankara, 06590, Turkey (Türkiye)

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Ankara, Turkey (Türkiye)

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Istanbul, 34093, Turkey (Türkiye)

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Izmir, 35340, Turkey (Türkiye)

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Izmir, Turkey (Türkiye)

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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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Lviv, 79044, Ukraine

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Makiivka, 86132, Ukraine

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Vinnitsa, 21018, Ukraine

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Zhytomyr, 10002, Ukraine

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MeSH Terms

Conditions

Leukemia, B-Cell

Interventions

ofatumumab; Observation

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

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
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2009
• First Posted: December 25, 2009
• Study Start: May 6, 2010
• Primary Completion: February 20, 2017
• Study Completion: June 26, 2018
• Last Updated: July 30, 2019
• Results First Posted: April 21, 2015

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will share

Locations

KR (5); ES (7); AR (6); SE (6); PL (9); UA (9); CZ (5); PR (1); IL (12); RU (9); TU (5); CA (7); HU (4); US (43); NO (1); AU (5); GR (5); BR (6); DK (3); FI (5); IN (4); BE (8); FR (12); IT (6); NL (20)