Ofatumumab vs Physician's Choice in Subjects With Bulky Fludarabine-Refractory Chronic Lymphocytic Leukemia

NCT ID: NCT01313689

Last Updated: 2018-11-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 122 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-14
• Study Completion Date: 2017-04-24

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.

Conditions

Leukaemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ofatumumab

Biological

Group Type: EXPERIMENTAL

Ofatumumab

Intervention Type: DRUG

Ofatumumab IV, initial dose 300 mg, followed 1 week later with 2000 mg once weekly for 7 weeks, followed 4 weeks later by one infusion of 2000 mg every 4 weeks for 4 infusions, for a total of 12 infusions over 24 weeks. After 24 weeks of ofatumumab treatment, patients who have achieved at least stable disease or better, and whom the investigator would deem appropriate for the therapy to continue, would undergo a second randomisation (2:1) to either 1) an additional ofatumumab dose regimen of 2000 mg once every 4 weeks for up to an additional 24 weeks, or 2) no further therapy (i.e. observation only).

Physicians' Choice

Physicians' choice of treatment

Group Type: ACTIVE_COMPARATOR

Physicians' Choice

Intervention Type: DRUG

Non-ofatumumab containing regimen as per physicians' choice for up to 6 months. Permitted therapies include treatments approved for CLL, and well established standards of care for CLL.

Interventions

Ofatumumab

Ofatumumab IV, initial dose 300 mg, followed 1 week later with 2000 mg once weekly for 7 weeks, followed 4 weeks later by one infusion of 2000 mg every 4 weeks for 4 infusions, for a total of 12 infusions over 24 weeks. After 24 weeks of ofatumumab treatment, patients who have achieved at least stable disease or better, and whom the investigator would deem appropriate for the therapy to continue, would undergo a second randomisation (2:1) to either 1) an additional ofatumumab dose regimen of 2000 mg once every 4 weeks for up to an additional 24 weeks, or 2) no further therapy (i.e. observation only).

Intervention Type: DRUG

Physicians' Choice

Non-ofatumumab containing regimen as per physicians' choice for up to 6 months. Permitted therapies include treatments approved for CLL, and well established standards of care for CLL.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Graz, , Austria

Novartis Investigative Site

Innsbruck, , Austria

Novartis Investigative Site

Linz, , Austria

Novartis Investigative Site

Salzburg, , Austria

Novartis Investigative Site

Vienna, , Austria

Novartis Investigative Site

Brussels, , Belgium

Novartis Investigative Site

Leuven, , Belgium

Novartis Investigative Site

Sofia, , Bulgaria

Novartis Investigative Site

Sofia, , Bulgaria

Novartis Investigative Site

Sofia, , Bulgaria

Novartis Investigative Site

Hradec Králové, , Czechia

Novartis Investigative Site

Olomouc, , Czechia

Novartis Investigative Site

Prague, , Czechia

Novartis Investigative Site

Bobigny, , France

Novartis Investigative Site

Brest, , France

Novartis Investigative Site

Clermont-Ferrand, , France

Novartis Investigative Site

Créteil, , France

Novartis Investigative Site

Lille, , France

Novartis Investigative Site

Rennes, , France

Novartis Investigative Site

Toulouse, , France

Novartis Investigative Site

Tours, , France

Novartis Investigative Site

Kronach, Bavaria, Germany

Novartis Investigative Site

Regensburg, Bavaria, Germany

Novartis Investigative Site

Frankfurt (Oder), Brandenburg, Germany

Novartis Investigative Site

Frankfurt am Main, Hesse, Germany

Novartis Investigative Site

Cologne, North Rhine-Westphalia, Germany

Novartis Investigative Site

Essen, North Rhine-Westphalia, Germany

Novartis Investigative Site

Koblenz, Rhineland-Palatinate, Germany

Novartis Investigative Site

Chemnitz, Saxony, Germany

Novartis Investigative Site

Dresden, Saxony, Germany

Novartis Investigative Site

Magdeburg, Saxony-Anhalt, Germany

Novartis Investigative Site

Budapest, , Hungary

Novartis Investigative Site

Debrecen, , Hungary

Novartis Investigative Site

Pécs, , Hungary

Novartis Investigative Site

Szombathely, , Hungary

Novartis Investigative Site

Dublin, , Ireland

Novartis Investigative Site

Galway, , Ireland

Novartis Investigative Site

James Street, , Ireland

Novartis Investigative Site

Jerusalem, , Israel

Novartis Investigative Site

Ramat Gan, , Israel

Novartis Investigative Site

Modena, Emilia-Romagna, Italy

Novartis Investigative Site

Brescia, Lombardy, Italy

Novartis Investigative Site

Milan, Lombardy, Italy

Novartis Investigative Site

Milan, Lombardy, Italy

Novartis Investigative Site

Turin, Piedmont, Italy

Novartis Investigative Site

Messina, Sicily, Italy

Novartis Investigative Site

Chorzów, , Poland

Novartis Investigative Site

Lodz, , Poland

Novartis Investigative Site

Wroclaw, , Poland

Novartis Investigative Site

Chelyabinsk, , Russia

Novartis Investigative Site

Moscow, , Russia

Novartis Investigative Site

Saint Petersburg, , Russia

Novartis Investigative Site

St'Petersburg, , Russia

Novartis Investigative Site

Singapore, , Singapore

Novartis Investigative Site

Bratislava, , Slovakia

Novartis Investigative Site

Bratislava, , Slovakia

Novartis Investigative Site

Košice, , Slovakia

Novartis Investigative Site

Martin, , Slovakia

Novartis Investigative Site

Gothenburg, , Sweden

Novartis Investigative Site

Linköping, , Sweden

Novartis Investigative Site

Luleå, , Sweden

Novartis Investigative Site

Örebro, , Sweden

Novartis Investigative Site

Stockholm, , Sweden

Novartis Investigative Site

Umeå, , Sweden

Novartis Investigative Site

Uppsala, , Sweden

Novartis Investigative Site

Cherkasy, , Ukraine

Novartis Investigative Site

Dnipropetrovsk, , Ukraine

Novartis Investigative Site

Donetsk, , Ukraine

Novartis Investigative Site

Kharkiv, , Ukraine

Novartis Investigative Site

Khmelnytskyi, , Ukraine

Novartis Investigative Site

Kyiv, , Ukraine

Novartis Investigative Site

Kyiv, , Ukraine

Novartis Investigative Site

Lviv, , Ukraine

Novartis Investigative Site

Makiivka, , Ukraine

Novartis Investigative Site

Simferopil, , Ukraine

Novartis Investigative Site

Vinnitsa, , Ukraine

Novartis Investigative Site

Zhytomyr, , Ukraine

Novartis Investigative Site

Bournemouth, , United Kingdom

Novartis Investigative Site

Manchester, , United Kingdom

Novartis Investigative Site

Oxford, , United Kingdom

Countries

Austria; Belgium; Bulgaria; Czechia; France; Germany; Hungary; Ireland; Israel; Italy; Poland; Russia; Singapore; Slovakia; Sweden; Ukraine; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 26784000 (View on PubMed)

Other Identifiers

114242

Identifier Type: -

Identifier Source: org_study_id