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| Name | Class |
|---|---|
| Janssen Research & Development, LLC | INDUSTRY |
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The purpose of this study is to evaluate the safety and efficacy of ibrutinib in combination with rituximab in participants with Waldenström's macroglobulinemia (WM).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Randomized Study (Ibrutinib + Rituximab) | Experimental | 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. |
|
| Randomized Study (Placebo + Rituximab) | Experimental | 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. |
|
| Open-Label Substudy (Ibrutinib) | Experimental | Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ibrutinib | Drug | Participants will receive 420 mg of Ibrutinib orally. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Progression Free Survival (PFS) Based on Independent Review Committee (IRC) Assessment - Kaplan Meier Landmark Estimates at Month 54 | PFS was defined as the time from date randomization to date of first IRC-confirmed disease progression (PD) assessed according to the modified VIth International Workshop on Waldenström's Macroglobulinemia (IWWM) criteria (National Comprehensive Cancer Network [NCCN] 2014) or death due to any cause, whichever occurs first, regardless of the use of subsequent antineoplastic therapy prior to documented PD or death. As the median PFS was not reached in the Ibrutinib + Rituximab arm at the time of the analysis, Kaplan Meier landmark estimate of the PFS rate at 54 months (that is, the estimated percentage of participants with PFS at Month 54) is presented. | Month 54 (median time on study: 49.7 months [Ibr+R and Pbo+R] and 57.9 months [Open-Label Ibr]) |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response Rate (ORR) Based on IRC Assessment Up to 3 Years After Last Participant Randomized | ORR, defined as the percentage of participants achieving a best overall response of protocol-specified complete response (CR), very good partial response (VGPR), or partial response (PR) per the IRC assessment at or prior to initiation of subsequent antineoplastic therapy and confirmed by 2 consecutive assessments. IRC assessment of response was conducted according to the modified VIth IWWM (NCCN 2014) criteria and incorporated assessments from the central radiology review. CR required complete resolution of lymphadenopathy/splenomegaly if present at baseline. VGPR and PR required reduction in lymphadenopathy/splenomegaly if present at baseline.. Kaplan-Meier estimate. |
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Eligibility Criteria for the Randomized Study
Inclusion Criteria:
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
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
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| Name | Affiliation | Role |
|---|---|---|
| Bernhard Hauns, MD | Pharmacyclics LLC. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California Los Angeles | Los Angeles | California | 90404 | United States | ||
| Stanford Cancer Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29856685 | Background | Dimopoulos MA, Tedeschi A, Trotman J, Garcia-Sanz R, Macdonald D, Leblond V, Mahe B, Herbaux C, Tam C, Orsucci L, Palomba ML, Matous JV, Shustik C, Kastritis E, Treon SP, Li J, Salman Z, Graef T, Buske C; iNNOVATE Study Group and the European Consortium for Waldenstrom's Macroglobulinemia. Phase 3 Trial of Ibrutinib plus Rituximab in Waldenstrom's Macroglobulinemia. N Engl J Med. 2018 Jun 21;378(25):2399-2410. doi: 10.1056/NEJMoa1802917. Epub 2018 Jun 1. | |
| 27956157 |
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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.
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Participants were randomized in a 1:1 ratio to receive ibrutinib + rituximab (Ibr+R) or placebo + rituximab (Pbo+R). Separately, participants refractory to treatment with rituximab were enrolled in an open-label ibrutinib monotherapy substudy to further investigate the safety and efficacy of ibrutinib.
This study was conducted in 48 sites (10 in the United States, 30 in Europe, 4 in Canada and 4 in Australia).
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| ID | Title | Description |
|---|---|---|
| FG000 | Ibrutinib + Rituximab | Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment. Rituximab: 375 mg/m^2 intravenous (IV) per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 9, 2015 | Oct 20, 2020 |
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| Placebo | Drug | Participants will receive placebo capsules orally. |
|
| Rituximab | Drug | Participants will receive rituximab 375 mg/m^2 IV. |
|
|
| Median time on study: 49.7 months (Ibr+R and Pbo+R) and 57.9 months (Open-Label Ibr) |
| Time to Next Treatment (TnT) Time From the Date of Randomization to the Start Date of Any Subsequent WM Treatment. | TTnT was measured from the date of randomization to the start date of any subsequent WM treatment. Participants without subsequent treatment were censored at the date of the last study visit. As the median TTnT was not reached in the Ibrutinib + Rituximab arm and the Open-Label Substudy arm at the time of the analysis, Kaplan Meier landmark estimate of the TTnT rate at 54 months (that is, the estimated percentage of participants not receiving subsequent WM treatment at Month 54) are presented. | Month 54 (median time on study: 49.7 months [Ibr+R and Pbo+R] and 57.9 months [Open-Label Ibr]) |
| Percentage of Participants With Sustained Hemoglobin (Hgb) Improvement Up to 3 Years After Last Participant Randomized | Percentage of participants achieving a sustained improvement in Hgb at or prior to initiation of subsequent antineoplastic therapy. Hgb improvement is defined as an increase of ≥ 2 g/dL over baseline regardless of baseline value, or an increase to >11 g/dL with a ≥0.5 g/dL improvement if baseline is ≤ 11 g/dL. Sustained Hgb improvement is defined as improvement that is sustained continuously for ≥ 56 days (8 weeks) without blood transfusion or growth factors, which includes hemoglobin > 110 g/L with at least a 5 g/L improvement if baseline ≤110 g/L or increase ≥20 g/L over baseline. | Median time on study: 49.7 months (Ibr+R and Pbo+R) and 57.9 months (Open-Label Ibr) |
| 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 | Percentage of participants with ≥ 3 points increase from baseline by Week 25 in the FACIT-Fatigue subscale score.The FACIT-Fatigue is a 13-item questionnaire that assesses participant reported fatigue and its impact upon daily activities and function over the past 7 days. Each of the 13 items of the FACIT-Fatigue Scale ranges from 0-4, with a range of possible total scores from 0 (extreme fatigue) to 52 (no fatigue). Scores below 30 indicate severe fatigue. | Baseline, 25 weeks |
| Overall Survival (OS) - Kaplan Meier Landmark Estimates at Month 54 | OS, defined as the time from the date of randomization to the date of death from any cause. All deaths observed as the time of the analysis were considered as events. For participants who were not known to have died at the time of the analysis, OS data were censored at the date last known alive. As the median OS was not reached in any treatment arm at the time of the analysis, Kaplan Meier point estimates of the OS rate (that is, the estimated percentage of participants still surviving at Month 54) are presented. | Month 54 (median time on study: 49.7 months [Ibr+R and Pbo+R] and 57.9 months [Open-Label Ibr]) |
| Palo Alto |
| California |
| 94305 |
| United States |
| Colorado Blood Cancer Institute | Denver | Colorado | 80218 | United States |
| Emory University Hospital | Atlanta | Georgia | 30322 | United States |
| Northwestern Memorial Hospital | Chicago | Illinois | 60611 | United States |
| Dana Farber Cancer Institute | Boston | Massachusetts | 02215 | United States |
| Hackensack University Medical Center | Hackensack | New Jersey | 07601 | United States |
| Memorial Sloan Kettering Cancer Center | New York | New York | 10065 | United States |
| Weill Cornell Medical Center | New York | New York | 10065 | United States |
| Vanderbilt University Medical Center | Nashville | Tennessee | 37204 | United States |
| The Canberra Hospital | Garran | Australian Capital Territory | 2605 | Australia |
| Concord Repartriation General Hospital | Concord | New South Wales | 2139 | Australia |
| Flinders Medical Center | Bedford Park | South Australia | 05042 | Australia |
| Peter MacCallum Cancer Center | Melbourne | Victoria | 3000 | Australia |
| Cross Cancer Institute | Edmonton | Alberta | T6G1Z2 | Canada |
| Queen Elizabeth II Health Sciences Center | Halifax | Nova Scotia | B3H 2Y9 | Canada |
| Princess Margaret Hospital | Toronto | Ontario | M5G 2M9 | Canada |
| McGill University Health Center | Montreal | Quebec | H4A3J1 | Canada |
| Institut Paoli-Calmettes | Marseille | Bouches-du-Rhône | 13273 | France |
| Centre Hospitalier de Saint Brieuc Hopital Yves le Foll | Saint-Brieuc | Finistère | 22027 | France |
| Hôtel Dieu | Nantes | Loire-Atlantique | 44093 | France |
| CHU de Nancy-Hopital Brabois Adulte | Vandœuvre-lès-Nancy | Meurthe-et-Moselle | 54511 | France |
| Hôpital Claude Huriez | Lille | Nord | 59037 | France |
| CHU Estaing | Clermont-Ferrand | Puy-de-Dôme | 63000 | France |
| Centre Hospitalier Lyon Sud | Pierre-Bénite | Rhône | 69495 | France |
| Hopital Henri Mondor | Créteil | 94010 | France |
| Hôpital Saint Louis | Paris | 75010 | France |
| Groupe Hospitalier Pitié Salpétrière | Paris | 75651 Cedex 13 | France |
| Stauferklinikum Schwäbisch Gmünd | Mutlangen | Baden-Wurttemberg | 73557 | Germany |
| Universitätsmedizin der Johannes Gutenberg-Universität Mainz | Mainz | Rhineland-Palatinate | 55131 | Germany |
| Universität Des Saarlandes | Homburg | Saarland | 66421 | Germany |
| DIAKO Evangelische Diakonie Krankenhaus gGmbH | Bremen | 28239 | Germany |
| LMU Klinikum der Universität München | München | 81377 | Germany |
| University General Hospital of Patras | Pátrai | Achaia | 26500 | Greece |
| Alexandra Hospital | Athens | Attica | 11528 | Greece |
| University General Hospital of Thessaloniki "AHEPA" | Thessaloniki | Macedonia | 54621 | Greece |
| Laiko General Hospital of Athens | Athens | 11527 | Greece |
| Azienda Ospedaliera Città della Salute e della Scienza di Torino | Turin | Piedmont | 10126 | Italy |
| Fondazione IRCCS CÃ Granda Ospedale Maggiore Policlinico | Milan | 20122 | Italy |
| ASST Grande Ospedale Metropolitano Niguarda | Milan | 20162 | Italy |
| ASST di Pavia - Fondazione IRCCS Policlinico San Matteo di Pavia | Pavia | 27100 | Italy |
| Azienda Ospedaliero Universitaria Santa Maria della Misericordia di Udine | Udine | 33100 | Italy |
| Hospital Universitari Germans Trias i Pujol | Badalona | Barcelona | 08916 | Spain |
| Hospital Universitario de Salamanca | Salamanca | Castille and León | 37007 | Spain |
| Hospital Clinic de Barcelona | Barcelona | 08036 | Spain |
| Hospital de La Santa Creu i Sant Pau | Barcelona | 08041 | Spain |
| Hospital Universitario Infanta Leonor | Madrid | 28031 | Spain |
| Royal Bournemouth Hospital | Bournemouth | Dorset | BH7 7DW | United Kingdom |
| Background |
| Dimopoulos MA, Trotman J, Tedeschi A, Matous JV, Macdonald D, Tam C, Tournilhac O, Ma S, Oriol A, Heffner LT, Shustik C, Garcia-Sanz R, Cornell RF, de Larrea CF, Castillo JJ, Granell M, Kyrtsonis MC, Leblond V, Symeonidis A, Kastritis E, Singh P, Li J, Graef T, Bilotti E, Treon S, Buske C; iNNOVATE Study Group and the European Consortium for Waldenstrom's Macroglobulinemia. Ibrutinib for patients with rituximab-refractory Waldenstrom's macroglobulinaemia (iNNOVATE): an open-label substudy of an international, multicentre, phase 3 trial. Lancet Oncol. 2017 Feb;18(2):241-250. doi: 10.1016/S1470-2045(16)30632-5. Epub 2016 Dec 10. |
| 40674744 | Derived | Guijosa A, Ramirez-Gamero A, Sarosiek S, Branagan AR, von Keudell G, Treon SP, Castillo JJ. Ibrutinib plus rituximab vs ibrutinib monotherapy in patients with Waldenstrom macroglobulinemia: a pooled analysis. Blood Adv. 2025 Sep 23;9(18):4705-4715. doi: 10.1182/bloodadvances.2025016536. |
| 36815271 | Derived | Buske C, Tedeschi A, Trotman J, Garcia-Sanz R, MacDonald D, Leblond V, Mahe B, Herbaux C, Matous JV, Tam CS, Heffner LT, Varettoni M, Palomba ML, Shustik C, Kastritis E, Treon SP, Ping J, Hauns B, Arango-Hisijara I, Dimopoulos MA. Plain Language Summary of the iNNOVATE study: ibrutinib plus rituximab is well-tolerated and effective in people with Waldenstrom's macroglobulinemia. Future Oncol. 2023 Feb;19(5):345-353. doi: 10.2217/fon-2022-1015. Epub 2023 Feb 23. |
| 34606378 | Derived | Buske C, Tedeschi A, Trotman J, Garcia-Sanz R, MacDonald D, Leblond V, Mahe B, Herbaux C, Matous JV, Tam CS, Heffner LT, Varettoni M, Palomba ML, Shustik C, Kastritis E, Treon SP, Ping J, Hauns B, Arango-Hisijara I, Dimopoulos MA. Ibrutinib Plus Rituximab Versus Placebo Plus Rituximab for Waldenstrom's Macroglobulinemia: Final Analysis From the Randomized Phase III iNNOVATE Study. J Clin Oncol. 2022 Jan 1;40(1):52-62. doi: 10.1200/JCO.21.00838. Epub 2021 Oct 4. |
| 34380643 | Derived | Trotman J, Buske C, Tedeschi A, Matous JV, MacDonald D, Tam CS, Tournilhac O, Ma S, Treon SP, Oriol A, Ping J, Briso EM, Arango-Hisijara I, Dimopoulos MA. Single-Agent Ibrutinib for Rituximab-Refractory Waldenstrom Macroglobulinemia: Final Analysis of the Substudy of the Phase III InnovateTM Trial. Clin Cancer Res. 2021 Nov 1;27(21):5793-5800. doi: 10.1158/1078-0432.CCR-21-1497. Epub 2021 Aug 11. |
| FG001 | Placebo + Rituximab | Placebo: 3 capsules of placebo orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment. Rituximab: 375 mg/m^2 IV per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab. |
| FG002 | Open-Label Substudy: Ibrutinib | Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment. Participants (rituximab refractory) were treated in an open-label substudy independently of the 2 randomized main treatment arms. |
| COMPLETED | On-study until study termination by sponsor. |
|
| NOT COMPLETED |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | Ibrutinib + Rituximab | Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment. Rituximab: 375 mg/m^2 IV per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab. |
| BG001 | Placebo + Rituximab | Placebo: 3 capsules of placebo orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment. Rituximab: 375 mg/m^2 IV per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab. |
| BG002 | Open-Label Substudy: Ibrutinib | Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment. Participants (rituximab refractory) were treated in an open-label substudy independently of the 2 randomized main treatment arms. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Progression Free Survival (PFS) Based on Independent Review Committee (IRC) Assessment - Kaplan Meier Landmark Estimates at Month 54 | PFS was defined as the time from date randomization to date of first IRC-confirmed disease progression (PD) assessed according to the modified VIth International Workshop on Waldenström's Macroglobulinemia (IWWM) criteria (National Comprehensive Cancer Network [NCCN] 2014) or death due to any cause, whichever occurs first, regardless of the use of subsequent antineoplastic therapy prior to documented PD or death. As the median PFS was not reached in the Ibrutinib + Rituximab arm at the time of the analysis, Kaplan Meier landmark estimate of the PFS rate at 54 months (that is, the estimated percentage of participants with PFS at Month 54) is presented. | Intent to Treat population: all randomized/enrolled participants | Posted | Number | 95% Confidence Interval | percentage of participants | Month 54 (median time on study: 49.7 months [Ibr+R and Pbo+R] and 57.9 months [Open-Label Ibr]) |
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| Secondary | Overall Response Rate (ORR) Based on IRC Assessment Up to 3 Years After Last Participant Randomized | ORR, defined as the percentage of participants achieving a best overall response of protocol-specified complete response (CR), very good partial response (VGPR), or partial response (PR) per the IRC assessment at or prior to initiation of subsequent antineoplastic therapy and confirmed by 2 consecutive assessments. IRC assessment of response was conducted according to the modified VIth IWWM (NCCN 2014) criteria and incorporated assessments from the central radiology review. CR required complete resolution of lymphadenopathy/splenomegaly if present at baseline. VGPR and PR required reduction in lymphadenopathy/splenomegaly if present at baseline.. Kaplan-Meier estimate. | Intent to Treat population: all randomized/enrolled participants | Posted | Number | percentage of participants | Median time on study: 49.7 months (Ibr+R and Pbo+R) and 57.9 months (Open-Label Ibr) |
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| Secondary | Time to Next Treatment (TnT) Time From the Date of Randomization to the Start Date of Any Subsequent WM Treatment. | TTnT was measured from the date of randomization to the start date of any subsequent WM treatment. Participants without subsequent treatment were censored at the date of the last study visit. As the median TTnT was not reached in the Ibrutinib + Rituximab arm and the Open-Label Substudy arm at the time of the analysis, Kaplan Meier landmark estimate of the TTnT rate at 54 months (that is, the estimated percentage of participants not receiving subsequent WM treatment at Month 54) are presented. | Intent to Treat population: all randomized/enrolled participants | Posted | Number | 95% Confidence Interval | percentage of participants | Month 54 (median time on study: 49.7 months [Ibr+R and Pbo+R] and 57.9 months [Open-Label Ibr]) |
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| Secondary | Percentage of Participants With Sustained Hemoglobin (Hgb) Improvement Up to 3 Years After Last Participant Randomized | Percentage of participants achieving a sustained improvement in Hgb at or prior to initiation of subsequent antineoplastic therapy. Hgb improvement is defined as an increase of ≥ 2 g/dL over baseline regardless of baseline value, or an increase to >11 g/dL with a ≥0.5 g/dL improvement if baseline is ≤ 11 g/dL. Sustained Hgb improvement is defined as improvement that is sustained continuously for ≥ 56 days (8 weeks) without blood transfusion or growth factors, which includes hemoglobin > 110 g/L with at least a 5 g/L improvement if baseline ≤110 g/L or increase ≥20 g/L over baseline. | Intent to Treat population: all randomized/enrolled participants | Posted | Number | percentage of participants | Median time on study: 49.7 months (Ibr+R and Pbo+R) and 57.9 months (Open-Label Ibr) |
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| Secondary | 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 | Percentage of participants with ≥ 3 points increase from baseline by Week 25 in the FACIT-Fatigue subscale score.The FACIT-Fatigue is a 13-item questionnaire that assesses participant reported fatigue and its impact upon daily activities and function over the past 7 days. Each of the 13 items of the FACIT-Fatigue Scale ranges from 0-4, with a range of possible total scores from 0 (extreme fatigue) to 52 (no fatigue). Scores below 30 indicate severe fatigue. | Intent to Treat population: all randomized/enrolled participants | Posted | Number | percentage of participants | Baseline, 25 weeks |
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| Secondary | Overall Survival (OS) - Kaplan Meier Landmark Estimates at Month 54 | OS, defined as the time from the date of randomization to the date of death from any cause. All deaths observed as the time of the analysis were considered as events. For participants who were not known to have died at the time of the analysis, OS data were censored at the date last known alive. As the median OS was not reached in any treatment arm at the time of the analysis, Kaplan Meier point estimates of the OS rate (that is, the estimated percentage of participants still surviving at Month 54) are presented. | Intent to Treat population: all randomized/enrolled participants | Posted | Number | 95% Confidence Interval | percentage of participants | Month 54 (median time on study: 49.7 months [Ibr+R and Pbo+R] and 57.9 months [Open-Label Ibr]) |
|
From first dose of study drug up to 30 days after the last dose of study drug. Median duration of treatment was 47.7 months for the Ibr+R arm, 15.5 months for the Pbo+R arm, and 40.7 months for the Open-Label Ibr arm.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ibrutinib + Rituximab | Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment. Rituximab: 375 mg/m^2 IV per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab. | 9 | 75 | 40 | 75 | 75 | 75 |
| EG001 | Placebo + Rituximab | Placebo: 3 capsules of placebo orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment. Rituximab: 375 mg/m^2 IV per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab. | 10 | 75 | 25 | 75 | 75 | 75 |
| EG002 | Open-Label Substudy: Ibrutinib | Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment. | 8 | 31 | 16 | 31 | 30 | 31 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Immune thrombocytopenic purpura | Blood and lymphatic system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Angina unstable | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Cardiac tamponade | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Coronary artery disease | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Left ventricular failure | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Myocardial ischaemia | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Pericarditis | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Prinzmetal angina | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Hypertrophic cardiomyopathy | Congenital, familial and genetic disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Ulcerative keratitis | Eye disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Faecalith | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Ileus | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Melaena | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Death | General disorders | MedDRA 22.1 | Systematic Assessment | Cause of death unknown |
|
| Fatigue | General disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Gait disturbance | General disorders | MedDRA 22.1 | Systematic Assessment |
| |
| General physical health deterioration | General disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Cholecystitis acute | Hepatobiliary disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Arthritis bacterial | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Atypical pneumonia | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Clostridium difficile colitis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Enterococcal sepsis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Erysipelas | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Escherichia sepsis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Hemianopia | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Orchitis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Osteomyelitis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Pneumonia bacterial | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Pneumonia pneumococcal | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Pneumonia viral | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Prostatic abscess | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Pulmonary sepsis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Respiratory syncytial virus infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Staphylococcal bacteraemia | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Staphylococcal sepsis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Streptococcal bacteraemia | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Subcutaneous abscess | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Urosepsis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Femur fracture | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Lower limb fracture | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Pelvic fracture | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Spinal fracture | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Subdural haematoma | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Tendon injury | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 22.1 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Fluid overload | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Lactic acidosis | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Breast cancer metastatic | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Fracture pain | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Mobility decreased | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Psoriatic arthropathy | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Soft tissue necrosis | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Synovial cyst | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Tendonitis | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Benign pancreatic neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 22.1 | Systematic Assessment |
| |
| Bing-Neel syndrome | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 22.1 | Systematic Assessment |
| |
| Breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 22.1 | Systematic Assessment |
| |
| Diffuse large B-cell lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 22.1 | Systematic Assessment |
| |
| Invasive lobular breast carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 22.1 | Systematic Assessment |
| |
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 22.1 | Systematic Assessment |
| |
| Renal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 22.1 | Systematic Assessment |
| |
| Small cell lung cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 22.1 | Systematic Assessment |
| |
| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 22.1 | Systematic Assessment |
| |
| Aphasia | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Haemorrhage intracranial | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Lumbar radiculopathy | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Prostatitis | Reproductive system and breast disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Bronchopneumopathy | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Lung disorder | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Purpura | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Circulatory collapse | Vascular disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 22.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Increased tendency to bruise | Blood and lymphatic system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Spontaneous haematoma | Blood and lymphatic system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Tinnitus | Ear and labyrinth disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Cataract | Eye disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Diplopia | Eye disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Eye irritation | Eye disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Lacrimation increased | Eye disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Photophobia | Eye disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Visual acuity reduced | Eye disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Vitreous detachment | Eye disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Vitreous floaters | Eye disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Gingival bleeding | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Folliculitis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Localised infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Paronychia | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Respiratory tract infection viral | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Traumatic haematoma | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Gout | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Iron deficiency | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 22.1 | Systematic Assessment |
| |
| Tumour flare | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 22.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Sciatica | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Actinic keratosis | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Onychoclasis | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Onycholysis | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Psoriasis | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Blood Creatinine Increased | Investigations | MedDRA 22.1 | Systematic Assessment |
| |
| Blood Uric Acid Increased | Investigations | MedDRA 22.1 | Systematic Assessment |
|
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Lori Styles | Pharmacyclics LLC, An AbbVie Company | (408) 215-3770 | lstyles@pcyc.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 21, 2019 | Oct 20, 2020 | SAP_001.pdf |
| ID | Term |
|---|---|
| D008258 | Waldenstrom Macroglobulinemia |
| D008223 | Lymphoma |
| D008228 | Lymphoma, Non-Hodgkin |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C551803 | ibrutinib |
| D000069283 | Rituximab |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
Not provided
Not provided
| >= 65 years old |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
Placebo: 3 capsules of placebo orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment.
Rituximab: 375 mg/m2 IV per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab.
| OG002 | Open-Label Substudy: Ibrutinib | Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment. Participants (rituximab refractory) were treated in an open-label substudy independently of the 2 randomized main treatment arms. |
|
|
|
| OG002 | Open-Label Substudy: Ibrutinib | Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment. Participants (rituximab refractory) were treated in an open-label substudy independently of the 2 randomized main treatment arms. |
|
|
|
| OG002 | Open-Label Substudy: Ibrutinib | Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment. Participants (rituximab refractory) were treated in an open-label substudy independently of the 2 randomized main treatment arms. |
|
|
|
| OG002 | Open-Label Substudy: Ibrutinib | Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment. Participants (rituximab refractory) were treated in an open-label substudy independently of the 2 randomized main treatment arms. |
|
|
|
| OG002 | Open-Label Substudy: Ibrutinib | Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment. Participants (rituximab refractory) were treated in an open-label substudy independently of the 2 randomized main treatment arms. |
|
|
|