Clinical trial NCT01313689: Ofatumumab vs Physician's Choice in Subjects With Bulky Fludarabine-Refractory Chronic Lymphocytic Leukemia
Official title: An Open Label, Multicenter Study Investigating the Safety and Efficacy of Ofatumumab Therapy Versus Physicians' Choice in Patients With Bulky Fludarabine-Refractory Chronic Lymphocytic Leukaemia (CLL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Leukaemia
Keywords: OMB157
Lymphocytic
Chronic
Safety
Refractory
Chronic Lymphocytic Leukemia
Oncology
Ofatumumab
Efficacy
Physicians' Choice
Bulky Fludarabine Refractory Chronic Lymphocytic Leukemia
CLL
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-03-14
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to confirm the clinical benefit observed in the pivotal registration study, Hx-CD20-406. The Committee for Medicinal Products for Human Use (CHMP) required that a randomized study be conducted in CLL patients with bulky fludarabine-refractory disease as a specific obligation for grant of conditional approval for ARZERRA™ in the European Union (EU). This study compared ofatumumab with the physicians' choice of therapy.

Detailed description: Patients with CLL that is refractory to fludarabine have few treatment options and a poor prognosis. There is a continued need for new therapies for these CLL patients, as demonstrated by the limited responses and substantial toxicities with existing therapies. This is supported by the lack of a consensus around standard of care treatment for CLL patients with bulky fludarabine-refractory disease. The objective of this study was to confirm the response rate and disease control in the refractory setting through a controlled trial comparing ofatumumab with the physicians' choice of therapy in fludarabine-refractory, bulky lymphadenopathy patients. After 24 weeks of treatment with ofatumumab, patients were further randomized to either extended ofatumumab treatment or observation. Patients on the physicians' choice arm had the option of receiving ofatumumab if they experience progressive disease.

Eligibility criteria: Inclusion Criteria:

* Adults with documented diagnosis of active CLL requiring treatment
* Bulky lymphadenopathy, defined as at least 1 lymph node \>5 cm
* Must be refractory to fludarabine treatment
* Age 18 yrs or older
* At least 2 prior therapies for CLL
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* Signed written informed consent

Exclusion Criteria:

* Prior allogeneic stem cell transplant at any time, or autologous stem cell transplant within 6 months
* Treatment with any unapproved drug substance or experimental therapy within 4 weeks, or currently participating in another interventional clinical study
* CLL transformation, prolymphocytic leukemia, or central nervous system (CNS) involvement of CLL
* Active autoimmune hemolytic anemia (AIHA) requiring treatment except if associated with progressive disease requiring anti-CLL treatment
* Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment
* Human immunodeficiency virus (HIV) positive
* Significant concurrent, uncontrolled medical condition
* Other past or current malignancy (with the exception of basal cell carcinoma of the skin or in situ carcinoma of the cervix or breast) unless the tumor was successfully treated with curative intent at least 2 years prior to trial entry
* Non-protocol corticosteroid usage except a maintenance dose corresponding to less than or equal to 10 mg prednisone
* Abnormal lab values: Creatinine \> 2.0 times upper normal limit (unless normal creatinine clearance), or total bilirubin \> 2.0 times upper normal limit (unless due to liver involvement of CLL or due to Gilbert's syndrome), or alanine transaminase (ALT) \> 2.5 times upper normal limit (unless due to liver involvement of CLL)
* Known or suspected hypersensitivity to ofatumumab
* Lactating or pregnant women or female patients of child-bearing potential (or male patients with such partners) not willing to use adequate contraception

Primary outcomes:
measure: Progression-free Survival (PFS) as Assessed by Independent Review Committee (IRC)
timeFrame: From the randomization date up to 60 months post the randomization date.
Secondary outcomes:
measure: Progression-free Survival (PFS) as Assessed by Investigator
timeFrame: From the randomization date up to 60 months post the randomization date.
measure: Overall Response Rate (ORR) as Assessed by the IRC
timeFrame: From the randomization date up to 60 months post the randomization date.
measure: Overall Response Rate (ORR) as Assessed by the Investigator
timeFrame: From the randomization date up to 60 months post the randomization date.
measure: Overall Survival
timeFrame: From the randomization date up to 60 months post the randomization date.
measure: Time to Progression as Assessed by IRC
timeFrame: From the randomization date up to 60 months post the randomization date.
measure: Time to Next Anti-cancer Therapy by Investigator
timeFrame: From the randomization date up to 60 months post the randomization date.
measure: Time to Response as Assessed by the IRC
timeFrame: From the randomization date up to 60 months post the randomization date.
measure: Duration of Response as Assessed by the IRC
timeFrame: From the randomization date up to 60 months post the randomization date.
measure: Number of Participants With Any Adverse Event (AE), Any Serious Adverse Event (SAE), Any Fatal Serious Adverse Event (FSAE), or Deaths
timeFrame: From the first dose of study medication to 60 days after the last dose of study medication and until follow-up for SAEs unless initiation of subsequent anti-CLL therapy
measure: Number of Participants With Any Adverse Event (AE) of Special Interest
timeFrame: From the first dose of study medication to 60 days after the last dose of study medication and until follow-up for SAEs unless initiation of subsequent anti-CLL therapy
measure: Mean Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM Over Time
timeFrame: Screening and every 3 months during treatment, every 6 months after last treatment until PD or until 42 Month Follow-up Visit
measure: Number of Participants Who Were Positive or Negative for Human Anti-Human Antibodies (HAHA) Post-OFA Therapy
timeFrame: From the randomization date up to 60 months post the randomization date.
measure: Changes From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, Chronic Lymphocytic Leukaemia 16 Item Module (EORTC QLQ-CLL 16)
timeFrame: From the randomization date up to 60 months post the randomization date.
measure: Mean Health Change Questionnaire (HCQ) Score
timeFrame: From the randomization date up to 60 months post the randomization date.
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Novartis Investigative Site
city: Innsbruck
country: Austria
facility: Novartis Investigative Site
city: Linz
country: Austria
facility: Novartis Investigative Site
city: Salzburg
country: Austria
facility: Novartis Investigative Site
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Hradec Kralove
country: Czechia
facility: Novartis Investigative Site
city: Olomouc
country: Czechia
facility: Novartis Investigative Site
city: Praha 2
country: Czechia
facility: Novartis Investigative Site
city: Bobigny cedex
country: France
facility: Novartis Investigative Site
city: Brest cedex
country: France
facility: Novartis Investigative Site
city: Clermont-Ferrand Cedex 1
country: France
facility: Novartis Investigative Site
city: Creteil cedex
country: France
facility: Novartis Investigative Site
city: Lille cedex
country: France
facility: Novartis Investigative Site
city: Rennes cedex 9
country: France
facility: Novartis Investigative Site
city: Toulouse cedex 9
country: France
facility: Novartis Investigative Site
city: Tours cedex 9
country: France
facility: Novartis Investigative Site
city: Kronach
country: Germany
facility: Novartis Investigative Site
state: Bayern
city: Regensburg
country: Germany
facility: Novartis Investigative Site
state: Bayern
city: Frankfurt/Oder
country: Germany
facility: Novartis Investigative Site
state: Brandenburg
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
state: Hessen
city: Essen
country: Germany
facility: Novartis Investigative Site
state: Nordrhein-Westfalen
city: Koeln
country: Germany
facility: Novartis Investigative Site
state: Nordrhein-Westfalen
city: Koblenz
country: Germany
facility: Novartis Investigative Site
state: Rheinland-Pfalz
city: Magdeburg
country: Germany
facility: Novartis Investigative Site
state: Sachsen-Anhalt
city: Chemnitz
country: Germany
facility: Novartis Investigative Site
state: Sachsen
city: Dresden
country: Germany
facility: Novartis Investigative Site
state: Sachsen
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Pecs
country: Hungary
facility: Novartis Investigative Site
city: Szombathely
country: Hungary
facility: Novartis Investigative Site
city: Dublin
country: Ireland
facility: Novartis Investigative Site
city: Galway
country: Ireland
facility: Novartis Investigative Site
city: James Street
country: Ireland
facility: Novartis Investigative Site
city: Jerusalem
country: Israel
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Modena
country: Italy
facility: Novartis Investigative Site
state: Emilia-Romagna
city: Brescia
country: Italy
facility: Novartis Investigative Site
state: Lombardia
city: Milano
country: Italy
facility: Novartis Investigative Site
state: Lombardia
city: Milano
country: Italy
facility: Novartis Investigative Site
state: Lombardia
city: Torino
country: Italy
facility: Novartis Investigative Site
state: Piemonte
city: Messina
country: Italy
facility: Novartis Investigative Site
state: Sicilia
city: Chorzow
country: Poland
facility: Novartis Investigative Site
city: Lodz
country: Poland
facility: Novartis Investigative Site
city: Wroclaw
country: Poland
facility: Novartis Investigative Site
city: Chelyabinsk
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: St'Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: St. Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
city: Kosice
country: Slovakia
facility: Novartis Investigative Site
city: Martin
country: Slovakia
facility: Novartis Investigative Site
city: Goteborg
country: Sweden
facility: Novartis Investigative Site
city: Linkoping
country: Sweden
facility: Novartis Investigative Site
city: Lulea
country: Sweden
facility: Novartis Investigative Site
city: Orebro
country: Sweden
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
city: Umea
country: Sweden
facility: Novartis Investigative Site
city: Uppsala
country: Sweden
facility: Novartis Investigative Site
city: Cherkasy
country: Ukraine
facility: Novartis Investigative Site
city: Dnipropetrovsk
country: Ukraine
facility: Novartis Investigative Site
city: Donetsk
country: Ukraine
facility: Novartis Investigative Site
city: Kharkiv
country: Ukraine
facility: Novartis Investigative Site
city: Khmelnytskyi
country: Ukraine
facility: Novartis Investigative Site
city: Kyiv
country: Ukraine
facility: Novartis Investigative Site
city: Kyiv
country: Ukraine
facility: Novartis Investigative Site
city: Lviv
country: Ukraine
facility: Novartis Investigative Site
city: Makiivka
country: Ukraine
facility: Novartis Investigative Site
city: Simferopil
country: Ukraine
facility: Novartis Investigative Site
city: Vinnitsa
country: Ukraine
facility: Novartis Investigative Site
city: Zhytomyr
country: Ukraine
facility: Novartis Investigative Site
city: Bournemouth
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
city: Oxford
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Osterborg A, Udvardy M, Zaritskey A, Andersson PO, Grosicki S, Mazur G, Kaplan P, Steurer M, Schuh A, Montillo M, Kryachok I, Middeke JM, Kulyaba Y, Rekhtman G, Gorczyca M, Daly S, Chang CN, Lisby S, Gupta I. Phase III, randomized study of ofatumumab versus physicians' choice of therapy and standard versus extended-length ofatumumab in patients with bulky fludarabine-refractory chronic lymphocytic leukemia. Leuk Lymphoma. 2016 Sep;57(9):2037-46. doi: 10.3109/10428194.2015.1122783. Epub 2016 Jan 19.