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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-004699-77 | EudraCT Number | ||
| 54179060CLL3011 | Other Identifier | Janssen Research & Development, LLC |
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| Name | Class |
|---|---|
| Pharmacyclics LLC. | INDUSTRY |
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The purpose of this study is to assess progression-free survival (PFS) from treatment with ibrutinib plus venetoclax (I+VEN) compared with obinutuzumab plus chlorambucil (G-Clb) as assessed by an Independent Review Committee (IRC).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment Arm A: Ibrutinib and Venetoclax (I+VEN) | Experimental | Participants will initially receive ibrutinib (420 mg [milligrams]/day) for 3 cycles. Venetoclax dose ramp up (from 20 to 400 mg over 5 weeks) will begin at Cycle 4 and the combination of ibrutinib and venetoclax will be given for 12 cycles (each cycle is equivalent to 28 days). Participants who subsequently develop progressive disease may enter to Subsequent Therapy Phase to receive single-agent ibrutinib until disease progression or unacceptable toxicity. |
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| Treatment Arm B: Chlorambucil and Obinutuzumab (G-Clb) | Active Comparator | Participants will receive chlorambucil and obinutuzumab (G-Clb) for 6 cycles. Participants will receive obinutuzumab, 1000 mg intravenously (IV) on Days 1, 8 and 15 of Cycle 1, and on Day 1 of Cycles 2 to 6 and chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight, on Days 1 and 15 of Cycles 1 to 6. Participants who subsequently develop progressive disease may enter to Subsequent Therapy Phase to receive single-agent ibrutinib until disease progression or unacceptable toxicity. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ibrutinib | Drug | Participants will receive ibrutinib 420 mg orally once daily up to 15 cycles. |
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| Measure | Description | Time Frame |
|---|---|---|
| Progression Free Survival (PFS) | PFS: time between date of randomization and date of disease progression, as assessed by IRC, or date of death due to any cause, whichever occurs first, regardless of use of subsequent anti-cancer therapy prior to PD or death using iWCLL2008 criteria : New enlarged lymph nodes >15 mm, new hepatomegaly or splenomegaly, or other organ infiltrates, bone lesion, ascites or pleural effusion due to CLL; >=50% increase in longest diameter (LDi) from nadir in existing lymph node (LDi >15 mm) or >=50% increase from nadir in sum of diameters of multiple nodes (and at least 1 node with LDi >15 mm); >=50% increase from nadir in enlargement of liver/spleen; >=50% increase from baseline in lymphocyte count (ALC; to >=5*10^9/L); or >=50% increase from nadir in ALC in >=2 serial assessments if ALC is >=30000*10^9/L and lymphocyte doubling time is rapid unless considered treatment-related lymphocytosis; new cytopenia attributable to CLL; transformation to more aggressive histology. | Up to 2 years 10 months |
| Measure | Description | Time Frame |
|---|---|---|
| Minimal Residual Disease (MRD) Negative Rate | MRD-negative rate is defined as the percentage of participants who achieved MRD-negative status (that is, less than [<] 1 chronic lymphocytic leukemia (CLL) cell per 10,000 leukocytes or <0.01 percentage [%]) in the bone marrow as assessed by next-generation sequencing (NGS). Participants with missing MRD data were considered MRD positive. | Up to 2 years 10 months |
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Inclusion Criteria:
Adult participants who are: (a) greater than or equal to (>=) 65 years old or, (b) 18 to 64 years old and have at least 1 of the following:
Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that meets International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria
Measurable nodal disease (by computed tomography [CT]), defined as at least one lymph node > 1.5 centimeter (cm) in longest diameter
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Grade less than or equal to (<=) 2
Active CLL/SLL requiring treatment per the iwCLL criteria
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Norton Cancer Institute | Louisville | Kentucky | 40207 | United States | ||
| John Theurer Cancer Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38319255 | Derived | Kater AP, Owen C, Moreno C, Follows G, Munir T, Levin MD, Benjamini O, Janssens A, Osterborg A, Robak T, Simkovic M, Stevens D, Voloshin S, Vorobyev V, Ysebaert L, Qin R, Steele AJ, Schuier N, Baeten K, Caces DB, Niemann CU. Fixed-Duration Ibrutinib-Venetoclax in Patients with Chronic Lymphocytic Leukemia and Comorbidities. NEJM Evid. 2022 Jul;1(7):EVIDoa2200006. doi: 10.1056/EVIDoa2200006. Epub 2022 May 13. | |
| 37944541 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment Arm A (Ibrutinib + Venetoclax) | Participants received ibrutinib 420 milligrams (mg) orally once daily for 3 cycles (each cycle is of 28 days) followed by the combination of ibrutinib 420 mg and venetoclax 400 mg orally once daily for 12 cycles (including a 5-week venetoclax dose ramp up starting in cycle 4). Participants who subsequently developed independent review committee (IRC)-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity. |
| 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 | Dec 19, 2019 | Feb 25, 2022 |
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| Venetoclax | Drug | Participants will receive venetoclax in combination with ibrutinib for a total of 12 cycles, beginning at Cycle 4. For the first 5 weeks of venetoclax treatment, the treatment dose will be ramped up from 20 to 400 mg. |
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| Chlorambucil | Drug | Participants will receive chlorambucil at a dose of 0.5 mg/kg body weight on Days 1 and 15 of Cycles 1 to 6. |
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| Obinutuzumab | Drug | Participant will receive obinutuzumab 1000 mg intravenously on Days 1, 8, and 15 of Cycle 1, and Day 1 of Cycles 2 to 6. |
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| Ibrutinib (as Subsequent Therapy) | Drug | Participants will receive ibrutinib 420 mg orally once daily until disease progression or unacceptable toxicity during the subsequent therapy phase. |
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| Complete Response Rate (CRR) | Complete response rate is defined as the percentage of participants who achieved complete response or complete response with an incomplete marrow recovery (CRi) on or prior to initiation of subsequent anti-leukemic therapy per the IRC assessment. International Workshop on Chronic Lymphocytic Leukemia (iWCLL) 2008 criteria: CR- No lymphadenopathy and hepatosplenomegaly, no constitutional symptoms, neutrophils >1.5*10^9/liter (L), platelets >100*10^9/L, Hgb >11 gram per deciliter (g/dL), absolute lymphocyte count <4000/microliter (mcL) and normocellular bone marrow with <30% lymphocytes and no B lymphoid nodules; CRi- CR with incomplete recovery of bone marrow. | Up to 2 years 10 months |
| Overall Response Rate (ORR) | ORR: percentage of participants who achieved best overall response of either CR, CRi, nodular PR (nPR) and partial response (PR). iWCLL 2008 criteria: CR- No lymphadenopathy and hepatosplenomegaly, no constitutional symptoms, neutrophils >1.5*10^9/liter (L), platelets >100*10^9/L, Hgb >11 g/dL and ALC <4000/mcL, normocellular bone marrow with <30% lymphocytes and no B lymphoid nodules; CRi- CR with incomplete recovery of bone marrow; nPR- participants meet criteria for CR, but bone marrow biopsy shows B-lymphoid nodules (reflecting residual disease); PR-2 of following when abnormal at baseline: >=50% decrease in ALC, >=50% decrease in sum of products of multiple nodes, >=50% decrease in enlargement of spleen or liver; and 1 of following: neutrophils >1.5*10^9/L, Platelets >100*10^9/L and Hgb>11 g/dL or >=50% improvement over baseline in any of these; 50% reduction in bone marrow infiltrates or B lymphoid nodules; no new enlarged nodes or new hepatosplenomegaly. | Up to 2 years 10 months |
| Overall Survival (OS) | OS is defined as the time from date of randomization to date of death from any cause. | Up to 4 years 10 months |
| Duration of Response (DOR) | DOR is defined as the interval between the date of initial documentation of a response including partial response with lymphocytosis (PRL) and the date of first documented evidence of PD or death or date of censoring per the IRC assessment. iWCLL 2008 criteria for PD: New enlarged nodes >1.5 cm, new hepatomegaly or splenomegaly, or other organ infiltrates; >= 50% increase from nadir in existing lymph node or >=50% increase from nadir in sum of product of diameters of multiple nodes; >=50% increase from nadir in enlargement of liver or spleen; >=50% increase from baseline in lymphocyte count (and to >=5*10^9/L) unless considered treatment-related lymphocytosis; new cytopenia (Hemoglobin b or platelets) attributable to CLL; transformation to a more aggressive histology. | Up to 2 years 10 months |
| Time-to-Next Treatment | Time-to-next treatment was measured from the date of randomization to the start date of any subsequent anti-leukemic therapy. | Up to 2 years 10 months |
| Time to Worsening as Measured by Using EuroQol 5 Dimension 5 Level Questionnaire (EQ-5D-5L) | Time to worsening= time interval (months) from randomization to first observation of deterioration. EQ-5D-5L consists of a 5-item descriptive system and the EuroQol visual analog scale (EQ-5D VAS). EQ-5D-VAS self-rating records respondent's own assessment of his/her overall health status at time of completion, on scale of 0 (worst health you can imagine) to 100 (best health you can imagine). Worsening is defined as a decrease of >= 7 points (on a 0-100 scale). EQ-5D-5L descriptive system comprises 5 dimensions of health (mobility, self -care, usual activities, pain/discomfort, and anxiety/depression) to describe participant's current health state. Responses for 5 dimensions are combined into a 5-digit number describing respondents health state that can be converted into a single index value or utility score (using the United Kingdom weights), ranging from -1 to 1, where lower scores indicate a worse health status. Worsening is defined as a decrease of >=0.08 points (on a 0-1 scale). | Up to 2 years 10 months |
| Time to Worsening Measured by European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC QLQ)-C30) | Time to worsening= time interval from randomization to first observation of deterioration. EORTC QLQ-C30 includes 30 separate items: 5 functional scales (physical, role, emotional, cognitive, and social Functioning), 1 global health status (GHS) and QoL scale, 3 symptom scales (fatigue, nausea/vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Each item, except GHS, is answered on 4-point scale (1=not at all to 4=very much) and GHS is measured on 1-7 scale: 1=very poor and 7=excellent. Scores derived using validated scoring algorithms as per EORTC QLQ-C30 Manual and linearly transformed in a range from 0-100. For functional and global QoL scales, higher scores=better level of functioning/QoL. For symptom-oriented scales, higher score=more severe symptoms. Worsening in functional and global health scores=decrease of >=10 points (on 0-100 scale) and in symptom scores=increase of >=10 points (on 0-100 scale). | Up to 2 years 10 months |
| Time to Worsening and Time to Improvement as Measured by Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score | Responses to the 13-item FACIT Fatigue Scale are reported on a 5-point categorical response scale ranging from 0 (not at all) to 4 (very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score). Time to Worsening is defined as time interval (months) from randomization to first observation of deterioration. Worsening is defined as a decrease >= 3 points (on a 0-52 scale). Time to improvement is defined as the time interval (months) from randomization to the first observation of improvement. Improvement is defined as an increase >=3 points (on a 0-52 scale). | Up to 2 years 10 months |
| Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability | An adverse event (AE) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. | Up to 4 years 10 months |
| Number of Participants With Abnormal Clinical Laboratory Findings | Number of participants with abnormal clinical laboratory findings (hematology and serum chemistry) were reported. | Up to 4 years 10 months |
| Percentage of Participants With Sustained Hemoglobin Improvement | Sustained hemoglobin improvement is defined as the percentage of participants who achieved an increase in hemoglobin levels from baseline by >= 2 grams per deciliter (g/dL) and lasts for at least 56 days without blood transfusion or growth factors. | Up to 2 years 10 months |
| Percentage of Participants With Sustained Platelet Improvement | Sustained platelet improvement is defined as the percentage of participants who achieved an increase in platelet levels from baseline by >= 50% and lasts for at least 56 days without blood transfusion or growth factors. | Up to 2 years 10 months |
| Plasma Concentration of Ibrutinib and Venetoclax | Plasma concentrations of ibrutinib and venetoclax were determined by validated liquid chromatography-tandem mass spectrometry. | Ibrutinib: Pre-dose-Day 1 of Cycles 2, 3, 5 and 6 (each cycle is defined as 28 days), Venetoclax: Pre-dose-Day 1 of Cycles 5 and 6 |
| Hackensack |
| New Jersey |
| 07601 |
| United States |
| Novant Health | Charlotte | North Carolina | 28204 | United States |
| Institut - Jules Bordet | Anderlecht | 1070 | Belgium |
| ZNA Stuivenberg | Antwerp | 2060 | Belgium |
| Universitair Ziekenhuis Gent | Ghent | 9000 | Belgium |
| Virga Jessa Ziekenhuis | Hasselt | 3500 | Belgium |
| UZ Leuven Gasthuisberg | Leuven | 3000 | Belgium |
| Arthur J E Child Comprehensive Cancer Centre | Calgary | Alberta | T2N 5G2 | Canada |
| Cross Cancer Institute | Edmonton | Alberta | T6G 1Z2 | Canada |
| Juravinski Cancer Centre | Hamilton | Ontario | L8V 5C2 | Canada |
| The Ottawa Hospital - General Campus | Ottawa | Ontario | K1H 8L6 | Canada |
| CIUSSS de l Est de l Ile de Montreal Installation Hopital Maisonneuve Rosemont | Montreal | Quebec | H1T 2M4 | Canada |
| Jewish General Hospital | Montreal | Quebec | H3T 1E2 | Canada |
| Fakultni nemocnice Brno, Interni hematologicka a onkologicka klinika | Brno | 625 00 | Czechia |
| Fakultni nemocnice Hradec Kralove | Hradec Králové | 500 05 | Czechia |
| Fakultni Nemocnice Ostrava | Ostrava | 708 52 | Czechia |
| Fakultni nemocnice Plzen, Hemato-onkologicke oddeleni | Pilsen | 323 00 | Czechia |
| Vseobecna fakultni nemocnice v Praze - I. interni klinika - klinika hematologie | Prague | 128 08 | Czechia |
| Aalborg University Hospital | Aalborg | 9000 | Denmark |
| Aarhus Universitetshospital | Aarhus | 8200 | Denmark |
| Rigshospitalet 1 | Copenhagen | 2100 | Denmark |
| Rigshospitalet | Copenhagen | 2100 | Denmark |
| Odense Universitetshospital | Odense C | 5000 | Denmark |
| Roskilde Sygehus | Roskilde | DK- 4000 | Denmark |
| CHU de Clermont Ferrand | Clermont-Ferrand | 63000 | France |
| Hopital Claude Huriez | Lille | 59000 | France |
| CHU Montpellier | Montpellier | 34295 | France |
| Hopital Haut Leveque Service Maladie Du Sang | Pessac | 33604 | France |
| Centre Hospitalier Universitaire de Reims, Hôpital Robert Debré | Reims | 51100 | France |
| Institut Universitaire du Cancer Toulouse Oncopole | Toulouse | 31059 | France |
| CHU Bretonneau | Tours | 37044 | France |
| CHU-Nancy | Vandœuvre-lès-Nancy | 54511 | France |
| Institut Gustave Roussy | Villejuif | 94805 | France |
| Bnai Zion Medical Center | Haifa | 31048 | Israel |
| Carmel Medical Center | Haifa | 34362 | Israel |
| Hadassah Medical Center | Jerusalem | 9112001 | Israel |
| Western Galilee Medical Center | Nahariya | 22100 | Israel |
| Sheba Medical Center | Ramat Gan | 52621 | Israel |
| Tel Aviv Sourasky Medical Center | Tel Aviv | 64239 | Israel |
| Flevoziekenhuis | Almere Stad | 1315RA | Netherlands |
| OLVG | Amsterdam | 1091AC | Netherlands |
| Academic Medical Center | Amsterdam | 1105 AZ | Netherlands |
| Reinier de Graaf Gasthuis | Delft | 2625 AD | Netherlands |
| Albert Schweitzer Ziekenhuis | Dordrecht | 3318 AT | Netherlands |
| Catharinaziekenhuis | Eindhoven | 5623 EJ | Netherlands |
| Spaarne Gasthuis | Hoofddorp | 2134 TM | Netherlands |
| Zuyderland Medical Center | Sittard-Geleen | 6162 BG | Netherlands |
| Antonius hospital | Sneek | 8601 ZK | Netherlands |
| MC Haaglanden | The Hague | 2512 VA | Netherlands |
| Elisabeth zkh | Tilburg | 5022 GC | Netherlands |
| Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich | Chorzów | 41-500 | Poland |
| Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im M Kopernika w Lodzi | Lodz | 93 510 | Poland |
| Uniwersytecki Szpital Kliniczny Nr 1 w Lublinie | Lublin | 20-081 | Poland |
| Wojewodzki Szpital Specjalistyczny im Janusza Korczaka | Słupsk | 76-200 | Poland |
| Instytut Hematologii i Transfuzjologii | Warsaw | 02 776 | Poland |
| Moscow Multidisciplinary Scientific and Clinical Center named after S P Botkin | Moscow | 125284 | Russia |
| S.P. Botkin Moscow City Clinical Hospital | Moscow | 125284 | Russia |
| Nizhniy Novgorod Region Clinical Hospital | Nizhny Novgorod | 603126 | Russia |
| Ryazan Regional Clinical Hospital | Ryazan | 390039 | Russia |
| St.-Petersburg Clinical Research Institute of Hematology and Transfusiology | Saint Petersburg | 193024 | Russia |
| FSBIFederal Centre of Heart, Blood and Endocrinology named after V.A.Almazov MoH of the RF | Saint Petersburg | 197341 | Russia |
| Hosp Univ Vall D Hebron | Barcelona | 08035 | Spain |
| Hosp Clinic de Barcelona | Barcelona | 08036 | Spain |
| Hosp. de La Santa Creu I Sant Pau | Barcelona | 08041 | Spain |
| Hosp. Univ. de La Princesa | Madrid | 28006 | Spain |
| Hosp. Gral. Univ. Gregorio Maranon | Madrid | 28007 | Spain |
| Hosp. Univ. Infanta Leonor | Madrid | 28031 | Spain |
| Hospital Ramon y Cajal | Madrid | 28034 | Spain |
| Hosp Univ Fund Jimenez Diaz | Madrid | 28040 | Spain |
| Clinica Univ. de Navarra | Pamplona | 31008 | Spain |
| Hospital Clinico Universitario Salamanca | Salamanca | 37007 | Spain |
| Hosp. Virgen Del Rocio | Seville | 41013 | Spain |
| Sunderby Sjukhus Medicinkliniken | Luelå | 97180 | Sweden |
| Karolinska Universitetssjukhuset Solna, Centrum för Hematologi, Stockholm | Stockholm | 171 76 | Sweden |
| Gazi Universitesi Tip Fakultesi | Ankara | 06500 | Turkey (Türkiye) |
| Ankara Universitesi Tip Fakultesi Cebeci Arastirma ve Uygulama Hastanesi | Ankara | 06620 | Turkey (Türkiye) |
| V K V Amerikan Hastanesi | Istanbul | 34365 | Turkey (Türkiye) |
| Dokuz Eylul Universitesi Tip Fakultesi | Izmir | 35340 | Turkey (Türkiye) |
| Ondokuz Mayis Universitesi Tip Fakultesi Hastanesi | Samsun | 55280 | Turkey (Türkiye) |
| Birmingham Heartlands Hospital | Birmingham | B9 5ST | United Kingdom |
| Addenbrookes Hospital | Cambridge | CB2 0QQ | United Kingdom |
| Queen Mary University of London | Charterhouse Square | EC1M 6BQ | United Kingdom |
| New Victoria Hospital | Glasgow | G42 9LF | United Kingdom |
| St James's Hospital | Leeds | LS9 7T | United Kingdom |
| Derriford Hospital | Plymouth | PL6 8DH | United Kingdom |
| Barking Havering and Redbridge University Hospitals NHS Trust | Romford | RM7 0AG | United Kingdom |
| Royal Hallamshire Hospital | Sheffield | S10 2JF | United Kingdom |
| Derived |
| Niemann CU, Munir T, Moreno C, Owen C, Follows GA, Benjamini O, Janssens A, Levin MD, Robak T, Simkovic M, Voloshin S, Vorobyev V, Yagci M, Ysebaert L, Qi K, Qi Q, Sinet P, Parisi L, Srinivasan S, Schuier N, Baeten K, Howes A, Caces DB, Kater AP. Fixed-duration ibrutinib-venetoclax versus chlorambucil-obinutuzumab in previously untreated chronic lymphocytic leukaemia (GLOW): 4-year follow-up from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023 Dec;24(12):1423-1433. doi: 10.1016/S1470-2045(23)00452-7. Epub 2023 Nov 6. |
| 37315225 | Derived | Moreno C, Solman IG, Tam CS, Grigg A, Scarfo L, Kipps TJ, Srinivasan S, Mali RS, Zhou C, Dean JP, Szafer-Glusman E, Choi M. Immune restoration with ibrutinib plus venetoclax in first-line chronic lymphocytic leukemia: the phase 2 CAPTIVATE study. Blood Adv. 2023 Sep 26;7(18):5294-5303. doi: 10.1182/bloodadvances.2023010236. |
| FG001 | Treatment Arm B (Chlorambucil + Obinutuzumab) | Participants received chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight orally once daily on Days 1 and 15 of Cycles 1 to 6 in combination with obinutuzumab 1000 mgs intravenously (IV) once daily on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 to 6 (each cycle is of 28 days). Participants who subsequently developed IRC-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment Arm A (Ibrutinib + Venetoclax) | Participants received ibrutinib 420 milligrams (mg) orally once daily for 3 cycles (each cycle is of 28 days) followed by the combination of ibrutinib 420 mg and venetoclax 400 mg orally once daily for 12 cycles (including a 5-week venetoclax dose ramp up starting in cycle 4). Participants who subsequently developed independent review committee (IRC)-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity. |
| BG001 | Treatment Arm B (Chlorambucil + Obinutuzumab) | Participants received chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight orally once daily on Days 1 and 15 of Cycles 1 to 6 in combination with obinutuzumab 1000 mgs intravenously (IV) once daily on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 to 6 (each cycle is of 28 days). Participants who subsequently developed IRC-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | years |
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| 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 |
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| Region of Enrollment | Count of Participants | Participants |
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| 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Progression Free Survival (PFS) | PFS: time between date of randomization and date of disease progression, as assessed by IRC, or date of death due to any cause, whichever occurs first, regardless of use of subsequent anti-cancer therapy prior to PD or death using iWCLL2008 criteria : New enlarged lymph nodes >15 mm, new hepatomegaly or splenomegaly, or other organ infiltrates, bone lesion, ascites or pleural effusion due to CLL; >=50% increase in longest diameter (LDi) from nadir in existing lymph node (LDi >15 mm) or >=50% increase from nadir in sum of diameters of multiple nodes (and at least 1 node with LDi >15 mm); >=50% increase from nadir in enlargement of liver/spleen; >=50% increase from baseline in lymphocyte count (ALC; to >=5*10^9/L); or >=50% increase from nadir in ALC in >=2 serial assessments if ALC is >=30000*10^9/L and lymphocyte doubling time is rapid unless considered treatment-related lymphocytosis; new cytopenia attributable to CLL; transformation to more aggressive histology. | The intent-to-treat (ITT) analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received. | Posted | Median | 95% Confidence Interval | Months | Up to 2 years 10 months |
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| Secondary | Minimal Residual Disease (MRD) Negative Rate | MRD-negative rate is defined as the percentage of participants who achieved MRD-negative status (that is, less than [<] 1 chronic lymphocytic leukemia (CLL) cell per 10,000 leukocytes or <0.01 percentage [%]) in the bone marrow as assessed by next-generation sequencing (NGS). Participants with missing MRD data were considered MRD positive. | The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received. | Posted | Number | 95% Confidence Interval | Percentage of participants | Up to 2 years 10 months |
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| Secondary | Complete Response Rate (CRR) | Complete response rate is defined as the percentage of participants who achieved complete response or complete response with an incomplete marrow recovery (CRi) on or prior to initiation of subsequent anti-leukemic therapy per the IRC assessment. International Workshop on Chronic Lymphocytic Leukemia (iWCLL) 2008 criteria: CR- No lymphadenopathy and hepatosplenomegaly, no constitutional symptoms, neutrophils >1.5*10^9/liter (L), platelets >100*10^9/L, Hgb >11 gram per deciliter (g/dL), absolute lymphocyte count <4000/microliter (mcL) and normocellular bone marrow with <30% lymphocytes and no B lymphoid nodules; CRi- CR with incomplete recovery of bone marrow. | The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received. | Posted | Number | 95% Confidence Interval | Percentage of Participants | Up to 2 years 10 months |
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| Secondary | Overall Response Rate (ORR) | ORR: percentage of participants who achieved best overall response of either CR, CRi, nodular PR (nPR) and partial response (PR). iWCLL 2008 criteria: CR- No lymphadenopathy and hepatosplenomegaly, no constitutional symptoms, neutrophils >1.5*10^9/liter (L), platelets >100*10^9/L, Hgb >11 g/dL and ALC <4000/mcL, normocellular bone marrow with <30% lymphocytes and no B lymphoid nodules; CRi- CR with incomplete recovery of bone marrow; nPR- participants meet criteria for CR, but bone marrow biopsy shows B-lymphoid nodules (reflecting residual disease); PR-2 of following when abnormal at baseline: >=50% decrease in ALC, >=50% decrease in sum of products of multiple nodes, >=50% decrease in enlargement of spleen or liver; and 1 of following: neutrophils >1.5*10^9/L, Platelets >100*10^9/L and Hgb>11 g/dL or >=50% improvement over baseline in any of these; 50% reduction in bone marrow infiltrates or B lymphoid nodules; no new enlarged nodes or new hepatosplenomegaly. | The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received. Participants with missing post-randomization data were considered non-responders. | Posted | Number | 95% Confidence Interval | Percentage of participants | Up to 2 years 10 months |
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| Secondary | Overall Survival (OS) | OS is defined as the time from date of randomization to date of death from any cause. | The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. | Posted | Median | 95% Confidence Interval | Months | Up to 4 years 10 months |
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| Secondary | Duration of Response (DOR) | DOR is defined as the interval between the date of initial documentation of a response including partial response with lymphocytosis (PRL) and the date of first documented evidence of PD or death or date of censoring per the IRC assessment. iWCLL 2008 criteria for PD: New enlarged nodes >1.5 cm, new hepatomegaly or splenomegaly, or other organ infiltrates; >= 50% increase from nadir in existing lymph node or >=50% increase from nadir in sum of product of diameters of multiple nodes; >=50% increase from nadir in enlargement of liver or spleen; >=50% increase from baseline in lymphocyte count (and to >=5*10^9/L) unless considered treatment-related lymphocytosis; new cytopenia (Hemoglobin b or platelets) attributable to CLL; transformation to a more aggressive histology. | Population analyzed included ITT amongst who were responders (PR or better). | Posted | Median | 95% Confidence Interval | Months | Up to 2 years 10 months |
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| Secondary | Time-to-Next Treatment | Time-to-next treatment was measured from the date of randomization to the start date of any subsequent anti-leukemic therapy. | The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received. | Posted | Median | 95% Confidence Interval | Months | Up to 2 years 10 months |
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| Secondary | Time to Worsening as Measured by Using EuroQol 5 Dimension 5 Level Questionnaire (EQ-5D-5L) | Time to worsening= time interval (months) from randomization to first observation of deterioration. EQ-5D-5L consists of a 5-item descriptive system and the EuroQol visual analog scale (EQ-5D VAS). EQ-5D-VAS self-rating records respondent's own assessment of his/her overall health status at time of completion, on scale of 0 (worst health you can imagine) to 100 (best health you can imagine). Worsening is defined as a decrease of >= 7 points (on a 0-100 scale). EQ-5D-5L descriptive system comprises 5 dimensions of health (mobility, self -care, usual activities, pain/discomfort, and anxiety/depression) to describe participant's current health state. Responses for 5 dimensions are combined into a 5-digit number describing respondents health state that can be converted into a single index value or utility score (using the United Kingdom weights), ranging from -1 to 1, where lower scores indicate a worse health status. Worsening is defined as a decrease of >=0.08 points (on a 0-1 scale). | The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received. | Posted | Median | 95% Confidence Interval | Months | Up to 2 years 10 months |
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| Secondary | Time to Worsening Measured by European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC QLQ)-C30) | Time to worsening= time interval from randomization to first observation of deterioration. EORTC QLQ-C30 includes 30 separate items: 5 functional scales (physical, role, emotional, cognitive, and social Functioning), 1 global health status (GHS) and QoL scale, 3 symptom scales (fatigue, nausea/vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Each item, except GHS, is answered on 4-point scale (1=not at all to 4=very much) and GHS is measured on 1-7 scale: 1=very poor and 7=excellent. Scores derived using validated scoring algorithms as per EORTC QLQ-C30 Manual and linearly transformed in a range from 0-100. For functional and global QoL scales, higher scores=better level of functioning/QoL. For symptom-oriented scales, higher score=more severe symptoms. Worsening in functional and global health scores=decrease of >=10 points (on 0-100 scale) and in symptom scores=increase of >=10 points (on 0-100 scale). | The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received. | Posted | Median | 95% Confidence Interval | Months | Up to 2 years 10 months |
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| Secondary | Time to Worsening and Time to Improvement as Measured by Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score | Responses to the 13-item FACIT Fatigue Scale are reported on a 5-point categorical response scale ranging from 0 (not at all) to 4 (very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score). Time to Worsening is defined as time interval (months) from randomization to first observation of deterioration. Worsening is defined as a decrease >= 3 points (on a 0-52 scale). Time to improvement is defined as the time interval (months) from randomization to the first observation of improvement. Improvement is defined as an increase >=3 points (on a 0-52 scale). | The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received. | Posted | Median | 95% Confidence Interval | Months | Up to 2 years 10 months |
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| Secondary | Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability | An adverse event (AE) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. | The safety analysis set is defined as all randomized participants who received at least one dose of any one of the four study drugs (ibrutinib, venetoclax, chlorambucil, or obinutuzumab). | Posted | Count of Participants | Participants | Up to 4 years 10 months |
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| Secondary | Number of Participants With Abnormal Clinical Laboratory Findings | Number of participants with abnormal clinical laboratory findings (hematology and serum chemistry) were reported. | The safety analysis set is defined as all randomized participants who received at least one dose of any one of the four study drugs (ibrutinib, venetoclax, chlorambucil, or obinutuzumab). | Posted | Count of Participants | Participants | Up to 4 years 10 months |
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| Secondary | Percentage of Participants With Sustained Hemoglobin Improvement | Sustained hemoglobin improvement is defined as the percentage of participants who achieved an increase in hemoglobin levels from baseline by >= 2 grams per deciliter (g/dL) and lasts for at least 56 days without blood transfusion or growth factors. | The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received. | Posted | Number | Percentage of Participants | Up to 2 years 10 months |
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| Secondary | Percentage of Participants With Sustained Platelet Improvement | Sustained platelet improvement is defined as the percentage of participants who achieved an increase in platelet levels from baseline by >= 50% and lasts for at least 56 days without blood transfusion or growth factors. | The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received. | Posted | Number | Percentage of Participants | Up to 2 years 10 months |
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| Secondary | Plasma Concentration of Ibrutinib and Venetoclax | Plasma concentrations of ibrutinib and venetoclax were determined by validated liquid chromatography-tandem mass spectrometry. | The pharmacokinetics (PK) analysis set is defined as all randomized participants in Treatment Arm A who received at least one dose of ibrutinib and/or venetoclax and had at least one valid blood sample drawn for PK analysis. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this endpoint. Here, "n (number analyzed)" is defined as number of participants analyzed for specified category. | Posted | Mean | Standard Deviation | Nanograms per milliliter (ng/mL) | Ibrutinib: Pre-dose-Day 1 of Cycles 2, 3, 5 and 6 (each cycle is defined as 28 days), Venetoclax: Pre-dose-Day 1 of Cycles 5 and 6 |
|
Up to 4 years 10 months
The safety analysis set is defined as all randomized participants who received at least one dose of any one of the four study drugs (ibrutinib, venetoclax, chlorambucil, or obinutuzumab).
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment Arm A (Ibrutinib + Venetoclax) | Participants received ibrutinib 420 milligrams (mg) orally once daily for 3 cycles (each cycle is of 28 days) followed by the combination of ibrutinib 420 mg and venetoclax 400 mg orally once daily for 12 cycles (including a 5-week venetoclax dose ramp up starting in cycle 4). Participants who subsequently developed independent review committee (IRC)-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity. | 17 | 106 | 49 | 106 | 98 | 106 |
| EG001 | Treatment Arm B (Chlorambucil + Obinutuzumab) | Participants received chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight orally once daily on Days 1 and 15 of Cycles 1 to 6 in combination with obinutuzumab 1000 mgs intravenously (IV) once daily on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 to 6 (each cycle is of 28 days). Participants who subsequently developed IRC-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity. | 36 | 105 | 30 | 105 | 98 | 105 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Febrile Neutropenia | Blood and lymphatic system disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Acute Myocardial Infarction | Cardiac disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Angina Unstable | Cardiac disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Atrial Fibrillation | Cardiac disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Cardiac Arrest | Cardiac disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Cardiac Failure | Cardiac disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Cardiac Failure Congestive | Cardiac disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Myocardial Infarction | Cardiac disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Sinus Node Dysfunction | Cardiac disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Supraventricular Tachycardia | Cardiac disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Mesenteric Artery Thrombosis | Gastrointestinal disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Oesophagitis | Gastrointestinal disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Oedema Peripheral | General disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Sudden Death | General disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Cholecystitis Acute | Hepatobiliary disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Cholecystitis Chronic | Hepatobiliary disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Cholestasis | Hepatobiliary disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Gallbladder Rupture | Hepatobiliary disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Cytokine Release Syndrome | Immune system disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Bronchopulmonary Aspergillosis | Infections and infestations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Clostridium Colitis | Infections and infestations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Covid-19 Pneumonia | Infections and infestations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Erysipelas | Infections and infestations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Escherichia Urinary Tract Infection | Infections and infestations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Gastrointestinal Infection | Infections and infestations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Pneumococcal Sepsis | Infections and infestations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Pneumonia Cytomegaloviral | Infections and infestations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Respiratory Tract Infection | Infections and infestations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Septic Shock | Infections and infestations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Tonsillitis | Infections and infestations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Urinary Tract Infection | Infections and infestations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Femoral Neck Fracture | Injury, poisoning and procedural complications | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Hip Fracture | Injury, poisoning and procedural complications | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Infusion Related Reaction | Injury, poisoning and procedural complications | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Multiple Injuries | Injury, poisoning and procedural complications | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Overdose | Injury, poisoning and procedural complications | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Spinal Compression Fracture | Injury, poisoning and procedural complications | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Wound Necrosis | Injury, poisoning and procedural complications | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Alanine Aminotransferase Increased | Investigations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Aspartate Aminotransferase Increased | Investigations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Blood Phosphorus Increased | Investigations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Neutrophil Count Decreased | Investigations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Hyperphosphataemia | Metabolism and nutrition disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Iron Deficiency | Metabolism and nutrition disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Tumour Lysis Syndrome | Metabolism and nutrition disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Musculoskeletal Chest Pain | Musculoskeletal and connective tissue disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Polyarthritis | Musculoskeletal and connective tissue disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Adenocarcinoma Gastric | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Hepatocellular Carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Lung Neoplasm Malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Myelodysplastic Syndrome | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Myeloproliferative Neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Neoplasm Malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Uterine Leiomyoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Cerebral Haemorrhage | Nervous system disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Ischaemic Stroke | Nervous system disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Spinal Cord Compression | Nervous system disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Toxic Encephalopathy | Nervous system disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Major Depression | Psychiatric disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Mental Disorder | Psychiatric disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Acute Kidney Injury | Renal and urinary disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Chronic Kidney Disease | Renal and urinary disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Chronic Obstructive Pulmonary Disease | Respiratory, thoracic and mediastinal disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Dyspnoea Exertional | Respiratory, thoracic and mediastinal disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Pulmonary Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Dermatitis Bullous | Skin and subcutaneous tissue disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Pyoderma Gangrenosum | Skin and subcutaneous tissue disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Hypertensive Urgency | Vascular disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Venous Thrombosis | Vascular disorders | MedDRA Version 23.0 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Atrial Fibrillation | Cardiac disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Abdominal Pain | Gastrointestinal disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Mouth Ulceration | Gastrointestinal disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Oedema Peripheral | General disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Upper Respiratory Tract Infection | Infections and infestations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Urinary Tract Infection | Infections and infestations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Infusion Related Reaction | Injury, poisoning and procedural complications | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Alanine Aminotransferase Increased | Investigations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Aspartate Aminotransferase Increased | Investigations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Neutrophil Count Decreased | Investigations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Weight Decreased | Investigations | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Decreased Appetite | Metabolism and nutrition disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Hyperphosphataemia | Metabolism and nutrition disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Muscle Spasms | Musculoskeletal and connective tissue disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Pain in Extremity | Musculoskeletal and connective tissue disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Dizziness Postural | Nervous system disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Onychoclasis | Skin and subcutaneous tissue disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA Version 23.0 | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA Version 23.0 | Non-systematic Assessment |
|
If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| EXECUTIVE MEDICAL DIRECTOR | Janssen Research & Development, LLC | 844-434-4210 | ClinicalTrialDisclosure@its.jnj.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 16, 2021 | Feb 25, 2022 | SAP_001.pdf |
| ID | Term |
|---|---|
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| ID | Term |
|---|---|
| D015448 | Leukemia, B-Cell |
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C551803 | ibrutinib |
| C579720 | venetoclax |
| D002699 | Chlorambucil |
| C543332 | obinutuzumab |
| ID | Term |
|---|---|
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
Not provided
Not provided
| 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 |
|
| CANADA |
|
| CZECH REPUBLIC |
|
| DENMARK |
|
| FRANCE |
|
| ISRAEL |
|
| NETHERLANDS |
|
| POLAND |
|
| RUSSIAN FEDERATION |
|
| SPAIN |
|
| SWEDEN |
|
| TURKEY |
|
| UNITED KINGDOM |
|
| UNITED STATES |
|
|
|
| Treatment Arm B (Chlorambucil + Obinutuzumab) |
Participants received chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight orally once daily on Days 1 and 15 of Cycles 1 to 6 in combination with obinutuzumab 1000 mgs intravenously (IV) once daily on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 to 6 (each cycle is of 28 days). Participants who subsequently developed IRC-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity. |
|
|
| OG001 | Treatment Arm B (Chlorambucil + Obinutuzumab) | Participants received chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight orally once daily on Days 1 and 15 of Cycles 1 to 6 in combination with obinutuzumab 1000 mgs intravenously (IV) once daily on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 to 6 (each cycle is of 28 days). Participants who subsequently developed IRC-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity. |
|
|
|
|
| OG001 |
| Treatment Arm B (Chlorambucil + Obinutuzumab) |
Participants received chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight orally once daily on Days 1 and 15 of Cycles 1 to 6 in combination with obinutuzumab 1000 mgs intravenously (IV) once daily on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 to 6 (each cycle is of 28 days). Participants who subsequently developed IRC-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity. |
|
|
|
|
| OG001 | Treatment Arm B (Chlorambucil + Obinutuzumab) | Participants received chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight orally once daily on Days 1 and 15 of Cycles 1 to 6 in combination with obinutuzumab 1000 mgs intravenously (IV) once daily on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 to 6 (each cycle is of 28 days). Participants who subsequently developed IRC-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity. |
|
|
| OG001 | Treatment Arm B (Chlorambucil + Obinutuzumab) | Participants received chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight orally once daily on Days 1 and 15 of Cycles 1 to 6 in combination with obinutuzumab 1000 mgs intravenously (IV) once daily on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 to 6 (each cycle is of 28 days). Participants who subsequently developed IRC-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity. |
|
|
| OG001 | Treatment Arm B (Chlorambucil + Obinutuzumab) | Participants received chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight orally once daily on Days 1 and 15 of Cycles 1 to 6 in combination with obinutuzumab 1000 mgs intravenously (IV) once daily on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 to 6 (each cycle is of 28 days). Participants who subsequently developed IRC-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity. |
|
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|
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| Counts |
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| Participants |
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