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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01578707




Registration number
NCT01578707
Ethics application status
Date submitted
11/04/2012
Date registered
17/04/2012
Date last updated
8/04/2019

Titles & IDs
Public title
A Phase 3 Study of Ibrutinib (PCI-32765) Versus Ofatumumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
Scientific title
A Randomized, Multicenter, Open-label, Phase 3 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib (PCI-32765) Versus Ofatumumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Secondary ID [1] 0 0
2012-000694-23
Secondary ID [2] 0 0
PCYC-1112-CA
Universal Trial Number (UTN)
Trial acronym
RESONATE™
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed or Refractory Chronic Lymphocytic Leukemia 0 0
Small Lymphocytic Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ofatumumab
Treatment: Drugs - ibrutinib

Active Comparator: Ofatumumab (Arm A) - An anti-CD20 monoclonal antibody

Experimental: ibrutinib (Arm B) - A Bruton Tyrosine Kinase Inhibitor


Treatment: Drugs: ofatumumab
The ofatumumab (IV) dosage and schedule is 12 doses administered over 24 weeks or until disease progression, unacceptable toxicity.
Week 1: 300 mg initial dose Week 2 through 8: 2,000 mg (once weekly) Week 12, 16, 20 and 24: 2,000 mg (every 4 weeks)

Treatment: Drugs: ibrutinib
ibrutinib 420 mg (3 x 140-mg capsules) will be administered orally once daily until disease progression or unacceptable toxicity

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
PFS (Progression Free Survival) - The primary objective of this study was to evaluate the efficacy of ibrutinib compared to ofatumumab based on independent review committee (IRC) assessment of progression-free survival (PFS).
Progressive disease according to 2008 IWCLL guidelines was defined as:
Group A
Lymphadenopathy, increase =50%
Hepatomegaly, increase =50%
Splenomegaly, increase =50%
Blood lymphocytes, increase = 50% over baseline
Group B
Platelets counts, decrease of = 50% from baseline secondary to CLL
Hemoglobin, decrease of > 2 g/dL from baseline secondary to CLL
Timepoint [1] 0 0
Analysis was conducted after observing approximately 117 PFS events, which occurred about 18 months after the first subject was enrolled.
Secondary outcome [1] 0 0
OS (Overall Survival)
Timepoint [1] 0 0
OS analysis was conducted at the time of the interim PFS analysis, which was about 18 months after the first subject was enrolled.
Secondary outcome [2] 0 0
Hematological Improvements
Timepoint [2] 0 0
2 years

Eligibility
Key inclusion criteria
- ECOG performance status of 0-1.

- Diagnosis of CLL or SLL that meets IWCLL 2008 criteria.

- Active disease meeting at least 1 of the IWCLL 2008 criteria for requiring treatment.

- Must have received at least one prior therapy for CLL/SLL.

- Considered not appropriate for treatment or retreatment with purine analog based
therapy.

- Measurable nodal disease by CT.

- Patients must be able to receive outpatient treatment and laboratory monitoring at the
institution that administers study drug for the entire study.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Known CNS lymphoma or leukemia.

- No documentation of cytogenetic and/or FISH in patient records prior to first dose of
study drug.

- Any history of Richter's transformation or prolymphocytic leukemia.

- Uncontrolled Autoimmune Hemolytic Anemia (AIHA) or idiopathic thrombocytopenia purpura
(ITP).

- Prior exposure to ofatumumab or to ibrutinib.

- Prior autologous transplant within 6 months prior to first dose of study drug.

- Prior allogeneic stem cell transplant within 6 months or with any evidence of active
graft versus host disease or requirement for immunosuppressants within 28 days prior
to first dose of study drug.

- History of prior malignancy, with the exception of certain skin cancers and
malignancies treated with curative intent and with no evidence of active disease for
more than 3 years.

- Serologic status reflecting active hepatitis B or C infection.

- Unable to swallow capsules or disease significantly affecting gastrointestinal
function.

- Uncontrolled active systemic fungal, bacterial, viral, or other infection.

- History of stroke or intracranial hemorrhage within 6 months prior to the first dose
of study drug.

- Requires anticoagulation with warfarin.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Site # 500 - St. Leonards
Recruitment hospital [2] 0 0
Site # 503 - Brisbane
Recruitment hospital [3] 0 0
Site # 199 - East Melbourne
Recruitment hospital [4] 0 0
Site # 501 - Fitzroy
Recruitment hospital [5] 0 0
Site # 502 - Nedlands
Recruitment postcode(s) [1] 0 0
2065 - St. Leonards
Recruitment postcode(s) [2] 0 0
4102 - Brisbane
Recruitment postcode(s) [3] 0 0
3002 - East Melbourne
Recruitment postcode(s) [4] 0 0
3109 - Fitzroy
Recruitment postcode(s) [5] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
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United States of America
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Connecticut
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Georgia
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United States of America
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Indiana
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Massachusetts
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Michigan
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Minnesota
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New Jersey
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New York
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Ohio
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Pennsylvania
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South Carolina
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Tennessee
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Texas
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Virginia
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United States of America
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Washington
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Austria
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Graz
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Austria
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Linz
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Austria
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Salzburg
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Austria
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Vienna
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Austria
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Wein
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Austria
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Wels
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Belgium
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Antwerpen
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France
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Argenteuil
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France
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Bobigny
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France
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Bordeaux
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France
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Caen
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France
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Clermont Ferrand
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France
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Marseille
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France
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Nantes
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France
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Rennes
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France
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Vandœuvre-lès-Nancy
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Ireland
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Dublin
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Ireland
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Galway
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Italy
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Milano
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Italy
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Modena
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Italy
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Padova
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Poland
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Gdansk
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Poland
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Lodz
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Spain
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Barcelona
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Spain
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Coruna
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Spain
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Madrid
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Spain
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Pamplona
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United Kingdom
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Essex
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United Kingdom
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Surrey
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United Kingdom
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Bournemouth
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United Kingdom
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Canterbury
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United Kingdom
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Cardiff
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United Kingdom
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Headington
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United Kingdom
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Leeds
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United Kingdom
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Liverpool
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London
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United Kingdom
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Nottingham
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United Kingdom
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Southampton
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United Kingdom
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Withington

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Pharmacyclics LLC.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Janssen Research & Development, LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of the study is to evaluate whether treatment with ibrutinib as a monotherapy
results in a clinically significant improvement in progression free survival (PFS) as
compared to treatment with ofatumumab in patients with relapsed or refractory Chronic
Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
Trial website
https://clinicaltrials.gov/show/NCT01578707
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Anita Szoke, MD
Address 0 0
Pharmacyclics LLC.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications