A Phase 3 Study of Ibrutinib (PCI-32765) Versus Ofatumumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

Small Lymphocytic Lymphoma Clinical Trial

— RESONATE™  

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01578707
• Other study ID #: PCYC-1112-CA
• Secondary ID: 2012-000694-23
• Status: Completed
• Phase: Phase 3
• Start date: June 2012
• Est. completion date: October 25, 2018

Study information

• Verified date: December 2019
• Source: Pharmacyclics LLC.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Description:

Study PCYC-1112-CA is 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.

Patients randomized to the ofatumumab arm may be considered to receive next subsequent therapy with ibrutinib.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 391
• Est. completion date: October 25, 2018
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

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.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Relapsed or Refractory Chronic Lymphocytic Leukemia
• Small Lymphocytic Lymphoma

Intervention

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

Locations

Country	Name	City	State
Australia	Site # 503	Brisbane	Queensland
Australia	Site # 199	East Melbourne	Victoria
Australia	Site # 501	Fitzroy	Victoria
Australia	Site # 502	Nedlands	Western Australia
Australia	Site # 500	St. Leonards	New South Wales
Austria	Site # 509	Graz
Austria	Site # 508	Linz
Austria	Site # 504	Salzburg
Austria	Site # 505	Vienna
Austria	Site # 506	Wein
Austria	Site # 507	Wels
Belgium	Site # 393	Antwerpen
France	Site # 519	Argenteuil
France	Site # 511	Bobigny
France	Site # 515	Bordeaux
France	Site # 516	Caen
France	Site # 513	Clermont Ferrand
France	Site # 510	Marseille
France	Site # 520	Nantes
France	Site # 518	Rennes
France	Site # 517	Vandœuvre-lès-Nancy
Ireland	Site # 528	Dublin
Ireland	Site # 570	Dublin
Ireland	Site # 096	Galway
Italy	Site # 522	Milano
Italy	Site # 523	Milano
Italy	Site # 526	Milano
Italy	Site # 524	Modena
Italy	Site # 527	Padova
Poland	Site # 529	Gdansk
Poland	Site # 531	Lodz
Spain	Site # 533	Barcelona
Spain	Site # 534	Barcelona
Spain	Site # 535	Barcelona
Spain	Site # 539	Coruna
Spain	Site # 536	Madrid
Spain	Site # 537	Madrid
Spain	Site # 540	Madrid
Spain	Site # 538	Pamplona
United Kingdom	Site # 551	Bournemouth
United Kingdom	Site # 553	Canterbury
United Kingdom	Site # 546	Cardiff
United Kingdom	Site # 549	Colchester	Essex
United Kingdom	Site # 554	Headington
United Kingdom	Site # 550	Leeds
United Kingdom	Site # 552	Liverpool
United Kingdom	Site # 544	London
United Kingdom	Site # 548	Nottingham
United Kingdom	Site # 545	Southampton
United Kingdom	Site # 543	Sutton	Surrey
United Kingdom	Site # 541	Withington
United States	Site # 349	Boston	Massachusetts
United States	Site # 390	Boston	Massachusetts
United States	Site # 391	Boston	Massachusetts
United States	Site # 210	Charlottesville	Virginia
United States	Site # 197	Cincinnati	Ohio
United States	Site # 217	Columbus	Ohio
United States	Site # 130	Detroit	Michigan
United States	Site # 379	Evansville	Indiana
United States	Site # 396	Greenville	South Carolina
United States	Site # 032	Houston	Texas
United States	Site #408	La Jolla	California
United States	Site # 381	Laredo	Texas
United States	Site #377	Los Angeles	California
United States	Site #107	Marietta	Georgia
United States	Site # 410	Nashville	Tennessee
United States	Site # 059	New Brunswick	New Jersey
United States	Site # 350	New Hyde Park	New York
United States	Site # 200	New York	New York
United States	Site #411	Norwalk	Connecticut
United States	Site # 402	Philadelphia	Pennsylvania
United States	Site # 127	Rochester	New York
United States	Site # 406	Rochester	Minnesota
United States	Site #403	Santa Maria	California
United States	Site # 404	Seattle	Washington
United States	Site #038	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Pharmacyclics LLC.	Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  France,  Ireland,  Italy,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Progression Free Survival (PFS) by Investigator With up to 6 Years of Study Follow-up	Long-Term Progression Free Survival as assessed by the investigator with up to 6 years of study follow-up	From study initiation to study closure, including up to 6 years of study follow-up
Other	Overall Response Rate (ORR) by Investigator	Overall response per the IWCLL 2008 criteria as assessed by Investigator with up to 6 years of study follow-up	From study initiation to study closure, including up to 6 years of study follow-up
Primary	PFS (Progression Free Survival) by Independent Review Committee (IRC), Limited to the Time of Primary Analysis 06 November 2013	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) according to 2008 IWCLL guidelines.	Analysis was conducted after observing approximately 117 PFS events, which occurred about 18 months after the first subject was enrolled.
Secondary	Overall Response Rate (ORR) by Independent Review Committee (IRC)	Overall Response Rate per the IWCLL 2008 criteria as assessed by IRC, limited to the time of primary analysis 06 November 2013	About 18 months after the first subject was enrolled
Secondary	OS (Overall Survival)	OS analysis was conducted at the time of study closure, with no adjustment for crossover from the ofatumumab arm to the ibrutinib arm	OS analysis was conducted at the time of study closure, including up to 6 years of study follow-up
Secondary	Rate of Sustained Hemoglobin and Platelet Improvement	Proportion of subjects with hemoglobin (HgB) increase >=20 g/L and platelet (PLT) increase >=50% over baseline continuously for >=56 days without blood transfusions or growth factors.	From study initiation to study closure, including up to 6 years of study follow-up