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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02165397




Registration number
NCT02165397
Ethics application status
Date submitted
9/06/2014
Date registered
17/06/2014

Titles & IDs
Public title
Ibrutinib With Rituximab in Adults With Waldenström's Macroglobulinemia
Scientific title
iNNOVATE Study: A Randomized, Double-Blind, Placebo- Controlled, Phase 3 Study of Ibrutinib or Placebo in Combination With Rituximab in Subjects With Waldenström's Macroglobulinemia
Secondary ID [1] 0 0
PCYC-1127-CA
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Waldenström's Macroglobulinemia 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
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ibrutinib
Treatment: Drugs - Placebo
Treatment: Drugs - Rituximab

Experimental: Randomized Study (Ibrutinib + Rituximab) - Ibrutinib: 420 mg (3 capsules x 140 mg) orally administered daily beginning from Day 1. Rituximab: 375 mg/m\^2 intravenous (IV) per package insert weekly for four consecutive weeks, followed by a second four-weekly rituximab course after a three-month interval.

Experimental: Randomized Study (Placebo + Rituximab) - Placebo: 3 capsules of placebo orally administered daily beginning from Day 1. Rituximab: 375 mg/m\^2 IV per package insert weekly for four consecutive weeks, followed by a second four-weekly rituximab course after a three-month interval.

Experimental: Open-Label Substudy (Ibrutinib) - Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1.


Treatment: Drugs: Ibrutinib
Participants will receive 420 mg of Ibrutinib orally.

Treatment: Drugs: Placebo
Participants will receive placebo capsules orally.

Treatment: Drugs: Rituximab
Participants will receive rituximab 375 mg/m\^2 IV.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS) Based on Independent Review Committee (IRC) Assessment - Kaplan Meier Landmark Estimates at Month 54
Timepoint [1] 0 0
Month 54 (median time on study: 49.7 months [Ibr+R and Pbo+R] and 57.9 months [Open-Label Ibr])
Secondary outcome [1] 0 0
Overall Response Rate (ORR) Based on IRC Assessment Up to 3 Years After Last Participant Randomized
Timepoint [1] 0 0
Median time on study: 49.7 months (Ibr+R and Pbo+R) and 57.9 months (Open-Label Ibr)
Secondary outcome [2] 0 0
Time to Next Treatment (TnT) Time From the Date of Randomization to the Start Date of Any Subsequent WM Treatment.
Timepoint [2] 0 0
Month 54 (median time on study: 49.7 months [Ibr+R and Pbo+R] and 57.9 months [Open-Label Ibr])
Secondary outcome [3] 0 0
Percentage of Participants With Sustained Hemoglobin (Hgb) Improvement Up to 3 Years After Last Participant Randomized
Timepoint [3] 0 0
Median time on study: 49.7 months (Ibr+R and Pbo+R) and 57.9 months (Open-Label Ibr)
Secondary outcome [4] 0 0
Percentage of Participants With = 3 Points Increase From Baseline by Week 25 in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Subscale Score
Timepoint [4] 0 0
Baseline, 25 weeks
Secondary outcome [5] 0 0
Overall Survival (OS) - Kaplan Meier Landmark Estimates at Month 54
Timepoint [5] 0 0
Month 54 (median time on study: 49.7 months [Ibr+R and Pbo+R] and 57.9 months [Open-Label Ibr])

Eligibility
Key inclusion criteria
Eligibility Criteria for the Randomized Study



* Untreated or previously treated for WM. Previously treated subjects must have either documented disease progression or had no response (stable disease) to the most recent treatment regimen
* Centrally confirmed clinicopathological diagnosis of WM
* Measurable disease defined as serum monoclonal immunoglobulin M (IgM) >0.5 g/dL
* Symptomatic disease meeting at least 1 of the recommendations from the Second International Workshop on Waldenström Macroglobulinemia for requiring treatment
* Hematology and biochemical values within protocol-defined limits
* Men and women = 18 years of age
* Eastern Cooperative Oncology Group (ECOG) performance status of = 2
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Known involvement of the central nervous system by WM
* Disease that is refractory to the last prior rituximab-containing therapy defined as either

* Relapse after the last rituximab-containing therapy < 12 months since last dose of rituximab, OR
* Failure to achieve at least a minor response (MR) after the last rituximab-containing therapy If the subject meets this exclusion criterion and therefore is excluded from the main randomized study, participation in the non randomized substudy (Arm C) may be considered
* Rituximab treatment within the last 12 months before the first dose of study drug
* Known anaphylaxis or (immunoglobulin E) IgE-mediated hypersensitivity to murine proteins or to any component of rituximab
* Prior exposure to ibrutinib or other Bruton's tyrosine kinase (BTK) inhibitors
* Known bleeding disorders (eg, von Willebrand's disease) or hemophilia
* History of stroke or intracranial hemorrhage within 12 months prior to enrollment.
* Any uncontrolled active systemic infection.
* Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk.
* Currently active, clinically significant cardiovascular disease
* Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor

Eligibility Criteria for Open-label Substudy Treatment Arm C

The inclusion/exclusion criteria for the substudy (Arm C) are identical to those described above for the randomized study but, to be eligible, subjects need to be considered refractory to the last prior rituximab-containing therapy defined as either

* Relapse after the last rituximab-containing therapy <12 months since last dose of rituximab, OR
* Failure to achieve at least a MR after the last rituximab-containing therapy.

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
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
7/07/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
7/11/2019
Sample size
Target
Accrual to date
Final
181
Recruitment in Australia
Recruitment state(s)
ACT,NSW,SA,VIC
Recruitment hospital [1] 0 0
The Canberra Hospital - Garran
Recruitment hospital [2] 0 0
Concord Repartriation General Hospital - Concord
Recruitment hospital [3] 0 0
Flinders Medical Center - Bedford Park
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Center - Melbourne
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
2139 - Concord
Recruitment postcode(s) [3] 0 0
05042 - Bedford Park
Recruitment postcode(s) [4] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
New Jersey
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
Canada
State/province [9] 0 0
Alberta
Country [10] 0 0
Canada
State/province [10] 0 0
Nova Scotia
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario
Country [12] 0 0
Canada
State/province [12] 0 0
Quebec
Country [13] 0 0
France
State/province [13] 0 0
Bouches-du-Rhône
Country [14] 0 0
France
State/province [14] 0 0
Finistère
Country [15] 0 0
France
State/province [15] 0 0
Loire-Atlantique
Country [16] 0 0
France
State/province [16] 0 0
Meurthe-et-Moselle
Country [17] 0 0
France
State/province [17] 0 0
Nord
Country [18] 0 0
France
State/province [18] 0 0
Puy-de-Dôme
Country [19] 0 0
France
State/province [19] 0 0
Rhône
Country [20] 0 0
France
State/province [20] 0 0
Créteil
Country [21] 0 0
France
State/province [21] 0 0
Paris
Country [22] 0 0
Germany
State/province [22] 0 0
Baden-Württemberg
Country [23] 0 0
Germany
State/province [23] 0 0
Rheinland-Pfalz
Country [24] 0 0
Germany
State/province [24] 0 0
Saarland
Country [25] 0 0
Germany
State/province [25] 0 0
Bremen
Country [26] 0 0
Germany
State/province [26] 0 0
München
Country [27] 0 0
Greece
State/province [27] 0 0
Achaia
Country [28] 0 0
Greece
State/province [28] 0 0
Attiki
Country [29] 0 0
Greece
State/province [29] 0 0
Macedonia
Country [30] 0 0
Greece
State/province [30] 0 0
Athens
Country [31] 0 0
Italy
State/province [31] 0 0
Piemonte
Country [32] 0 0
Italy
State/province [32] 0 0
Milano
Country [33] 0 0
Italy
State/province [33] 0 0
Pavia
Country [34] 0 0
Italy
State/province [34] 0 0
Udine
Country [35] 0 0
Spain
State/province [35] 0 0
Barcelona
Country [36] 0 0
Spain
State/province [36] 0 0
Castilla Y León
Country [37] 0 0
Spain
State/province [37] 0 0
Madrid
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Dorset

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
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bernhard Hauns, MD
Address 0 0
Pharmacyclics LLC (An AbbVie Company)
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Requests for access to individual participant data from clinical studies conducted by Pharmacyclics LLC, an AbbVie Company, can be submitted through Yale Open Data Access (YODA) Project site at the following link.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://yoda.yale.edu


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02165397