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

NCT01313689 | Completed Phase 3 Results

• 1 other identifier: 114242
• Study Type: interventional
• Target: 122
• Locations: 17 countries
• Sites: 80

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.

Conditions

Leukaemia

Keywords

OMB157; Lymphocytic; Chronic; Safety; Refractory; Chronic Lymphocytic Leukemia; Oncology; Ofatumumab; Efficacy; Physicians' Choice; Bulky Fludarabine Refractory Chronic Lymphocytic Leukemia; CLL

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) as Assessed by Independent Review Committee (IRC)

  PFS is the interval of time between the date of first randomization to the date of disease progression (PD) or death due to any reason, whichever occurred first. The date of PD was defined as the first occurrence of any criteria of progression. PD criteria requires at least one of the following: progression of lymphadenopathy, \>=50% increase in liver or spleen size, \>=50% increase in number of lymphocytes per microliter, more aggressive histology, occurence of cytopenia after treatment attributable to CLL. Disease progression was determined according to the 2008 International Workshop for Chronic Lymphocytic Leukaemia (IWCLL) update of the National Cancer Institute-sponsored Working Group CLL Guidelines for Response (NCI-WG). PFS was censored at the time of the last follow up for participants who have neither progressed or died.

  From the randomization date up to 60 months post the randomization date.

Secondary Outcomes (14)

• Progression-free Survival (PFS) as Assessed by Investigator

  From the randomization date up to 60 months post the randomization date.

• Overall Response Rate (ORR) as Assessed by the IRC

  From the randomization date up to 60 months post the randomization date.

• Overall Response Rate (ORR) as Assessed by the Investigator

  From the randomization date up to 60 months post the randomization date.

• Overall Survival

  From the randomization date up to 60 months post the randomization date.

• Time to Progression as Assessed by IRC

  From the randomization date up to 60 months post the randomization date.

Study Arms (2)

Ofatumumab

EXPERIMENTAL

Biological

Drug: Ofatumumab

Physicians' Choice

ACTIVE COMPARATOR

Physicians' choice of treatment

Drug: Physicians' Choice

Interventions

Ofatumumab 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).

Ofatumumab

Physicians' Choice 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.

Physicians' Choice

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (80)

Novartis Investigative Site

Graz, 8036, Austria

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Novartis Investigative Site

Innsbruck, 6020, Austria

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Novartis Investigative Site

Linz, 4020, Austria

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Salzburg, A-5020, Austria

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Vienna, 1140, Austria

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Novartis Investigative Site

Brussels, 1200, Belgium

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Leuven, 3000, Belgium

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Sofia, 1233, Bulgaria

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Sofia, 1407, Bulgaria

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Novartis Investigative Site

Sofia, 1431, Bulgaria

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Novartis Investigative Site

Hradec Králové, Czechia

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Novartis Investigative Site

Olomouc, 775 20, Czechia

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Novartis Investigative Site

Prague, 128 08, Czechia

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Novartis Investigative Site

Bobigny, 93009, France

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Novartis Investigative Site

Brest, 29609, France

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Novartis Investigative Site

Clermont-Ferrand, 63003, France

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Novartis Investigative Site

Créteil, 94010, France

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Novartis Investigative Site

Lille, 59037, France

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Rennes, 35033, France

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Toulouse, 31059, France

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Novartis Investigative Site

Tours, 37044, France

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Novartis Investigative Site

Kronach, Bavaria, 96317, Germany

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Novartis Investigative Site

Regensburg, Bavaria, 93053, Germany

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Novartis Investigative Site

Frankfurt (Oder), Brandenburg, 15236, Germany

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Novartis Investigative Site

Frankfurt am Main, Hesse, 60590, Germany

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Novartis Investigative Site

Cologne, North Rhine-Westphalia, 50937, Germany

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Novartis Investigative Site

Essen, North Rhine-Westphalia, 45122, Germany

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Novartis Investigative Site

Koblenz, Rhineland-Palatinate, 56068, Germany

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Novartis Investigative Site

Chemnitz, Saxony, 09113, Germany

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Novartis Investigative Site

Dresden, Saxony, 01307, Germany

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Novartis Investigative Site

Magdeburg, Saxony-Anhalt, 39130, Germany

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Novartis Investigative Site

Budapest, 1097, Hungary

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Debrecen, 4012, Hungary

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Pécs, 7624, Hungary

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Novartis Investigative Site

Szombathely, 9700, Hungary

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Novartis Investigative Site

Dublin, 7, Ireland

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Galway, Ireland

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Novartis Investigative Site

James Street, 8, Ireland

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Novartis Investigative Site

Jerusalem, 91120, Israel

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Novartis Investigative Site

Ramat Gan, 52621, Israel

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Novartis Investigative Site

Modena, Emilia-Romagna, 41124, Italy

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Novartis Investigative Site

Brescia, Lombardy, 25123, Italy

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Novartis Investigative Site

Milan, Lombardy, 20132, Italy

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Novartis Investigative Site

Milan, Lombardy, 20162, Italy

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Novartis Investigative Site

Turin, Piedmont, 10126, Italy

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Novartis Investigative Site

Messina, Sicily, 95158, Italy

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Novartis Investigative Site

Chorzów, 41-500, Poland

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Lodz, 93-510, Poland

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Novartis Investigative Site

Wroclaw, 50-367, Poland

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Novartis Investigative Site

Chelyabinsk, 454076, Russia

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Moscow, 115478, Russia

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Novartis Investigative Site

Saint Petersburg, 198205, Russia

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Novartis Investigative Site

St'Petersburg, 197341, Russia

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Novartis Investigative Site

Singapore, 169608, Singapore

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Novartis Investigative Site

Bratislava, 833 10, Slovakia

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Novartis Investigative Site

Bratislava, 851 07, Slovakia

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Novartis Investigative Site

Košice, 041 66, Slovakia

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Novartis Investigative Site

Martin, 036 59, Slovakia

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Novartis Investigative Site

Gothenburg, SE-413 45, Sweden

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Novartis Investigative Site

Linköping, SE-581 85, Sweden

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Novartis Investigative Site

Luleå, SE-971 80, Sweden

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Novartis Investigative Site

Örebro, SE-701 85, Sweden

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Novartis Investigative Site

Stockholm, SE-171 76, Sweden

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Novartis Investigative Site

Umeå, SE-901 85, Sweden

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Novartis Investigative Site

Uppsala, SE-751 85, Sweden

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Novartis Investigative Site

Cherkasy, 18009, Ukraine

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Novartis Investigative Site

Dnipropetrovsk, 49102, Ukraine

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Novartis Investigative Site

Donetsk, 83045, Ukraine

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Novartis Investigative Site

Kharkiv, 61070, Ukraine

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Novartis Investigative Site

Khmelnytskyi, 29000, Ukraine

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Novartis Investigative Site

Kyiv, 03022, Ukraine

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Novartis Investigative Site

Kyiv, 04112, Ukraine

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Novartis Investigative Site

Lviv, 79044, Ukraine

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Novartis Investigative Site

Makiivka, 86132, Ukraine

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Novartis Investigative Site

Simferopil, 95023, Ukraine

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Novartis Investigative Site

Vinnitsa, 21018, Ukraine

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Novartis Investigative Site

Zhytomyr, 10002, Ukraine

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Novartis Investigative Site

Bournemouth, BH7 7DW, United Kingdom

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Novartis Investigative Site

Manchester, M20 4BX, United Kingdom

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Novartis Investigative Site

Oxford, OX3 7LE, United Kingdom

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Related Publications (1)

• 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.

  PMID: 26784000 DERIVED

MeSH Terms

Conditions

Leukemia; Bronchiolitis Obliterans Syndrome; Leukemia, Lymphocytic, Chronic, B-Cell; Neoplasms

Interventions

ofatumumab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2011
• First Posted: March 14, 2011
• Study Start: April 14, 2011
• Primary Completion: March 18, 2014
• Study Completion: April 24, 2017
• Last Updated: November 8, 2018
• Results First Posted: November 24, 2014

Record last verified: 2018-10

Locations

IL (2); SE (7); GB (3); CZ (3); SG (1); UA (12); BU (3); PL (3); AU (5); BE (2); FR (8); IE (3); RU (4); IT (6); DE (10); HU (4); SL (4)