A Study of the Combination of Ibrutinib Plus Venetoclax Versus Chlorambucil Plus Obinutuzumab for the First-line Treatment of Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
Study Details
Study Description
Brief Summary
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).
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
Detailed Description
The hypothesis is treatment with combination of I+VEN will result in longer PFS compared with G-Clb in participants with previously untreated chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) who meet International Workshop on CLL (iwCLL) treatment criteria. The study includes screening (30 days), treatment (from randomization until treatment discontinuation) and follow-up phase (from treatment discontinuation until Subsequent Therapy Phase [if applicable], death, lost to follow up, consent withdrawal, or study end, whichever occurs first). Participants without progression will continue disease evaluations until disease progression or death. Participants from either treatment arm that develop progressive disease may be eligible to receive single-agent ibrutinib until disease progression or unacceptable toxicity (Subsequent Therapy Phase). Participation in this phase of the study is not mandatory and is based on investigator's discretion. Study duration is approximately 6 years. Safety includes review of adverse events and laboratory tests performed over time.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Treatment Arm A: Ibrutinib and Venetoclax (I+VEN) 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. |
Drug: Ibrutinib
Participants will receive ibrutinib 420 mg orally once daily up to 15 cycles.
Drug: Venetoclax
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.
Drug: Ibrutinib (as Subsequent Therapy)
Participants will receive ibrutinib 420 mg orally once daily until disease progression or unacceptable toxicity during the subsequent therapy phase.
|
Active Comparator: Treatment Arm B: Chlorambucil and Obinutuzumab (G-Clb) 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. |
Drug: Chlorambucil
Participants will receive chlorambucil at a dose of 0.5 mg/kg body weight on Days 1 and 15 of Cycles 1 to 6.
Drug: Obinutuzumab
Participant will receive obinutuzumab 1000 mg intravenously on Days 1, 8, and 15 of Cycle 1, and Day 1 of Cycles 2 to 6.
Drug: Ibrutinib (as Subsequent Therapy)
Participants will receive ibrutinib 420 mg orally once daily until disease progression or unacceptable toxicity during the subsequent therapy phase.
|
Outcome Measures
Primary Outcome Measures
- Progression Free Survival (PFS) [Up to 2 years 10 months]
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.
Secondary Outcome Measures
- Minimal Residual Disease (MRD) Negative Rate [Up to 2 years 10 months]
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.
- Complete Response Rate (CRR) [Up to 2 years 10 months]
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.
- Overall Response Rate (ORR) [Up to 2 years 10 months]
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.
- Overall Survival (OS) [Up to 3 years 4 months]
OS is defined as the time from date of randomization to date of death from any cause.
- Duration of Response (DOR) [Up to 2 years 10 months]
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.
- Time-to-Next Treatment [Up to 2 years 10 months]
Time-to-next treatment was measured from the date of randomization to the start date of any subsequent anti-leukemic therapy.
- Time to Worsening as Measured by Using EuroQol 5 Dimension 5 Level Questionnaire (EQ-5D-5L) [Up to 2 years 10 months]
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).
- Time to Worsening Measured by European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC QLQ)-C30) [Up to 2 years 10 months]
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).
- Time to Worsening and Time to Improvement as Measured by Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score [Up to 2 years 10 months]
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).
- Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability [Up to 3 years 4 months]
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.
- Number of Participants With Abnormal Clinical Laboratory Findings [Up to 2 years 10 months]
Number of participants with abnormal clinical laboratory findings (hematology and serum chemistry) were reported.
- Percentage of Participants With Sustained Hemoglobin Improvement [Up to 2 years 10 months]
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.
- Percentage of Participants With Sustained Platelet Improvement [Up to 2 years 10 months]
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.
- Plasma Concentration of Ibrutinib and Venetoclax [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]
Plasma concentrations of ibrutinib and venetoclax were determined by validated liquid chromatography-tandem mass spectrometry.
Eligibility Criteria
Criteria
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:
-
Cumulative Illness Rating Scale (CIRS) score > 6
-
Creatinine clearance (CrCl) estimated less than (<) 70 milliliter per minute (mL/min) using Cockcroft-Gault equation
-
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:
-
Prior anti-leukemic therapy for CLL or SLL
-
Presence of deletion of the short arm of chromosome 17 (del17p) or known TP53 mutation detected at a threshold of >10 percent (%) variable allele frequency (VAF)
-
Major surgery within 4 weeks of first dose of study treatment
-
Known bleeding disorders (example, von Willebrand's disease or hemophilia)
-
Central nervous system (CNS) involvement or suspected Richter's syndrome
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Norton Cancer Institute | Louisville | Kentucky | United States | 40207 |
2 | John Theurer Cancer Center | Hackensack | New Jersey | United States | 07601 |
3 | Novant Health | Charlotte | North Carolina | United States | 28204 |
4 | Institut - Jules Bordet | Anderlecht | Belgium | 1070 | |
5 | ZNA Stuivenberg | Antwerpen | Belgium | 2060 | |
6 | Universitair Ziekenhuis Gent | Gent | Belgium | 9000 | |
7 | Virga Jessa Ziekenhuis | Hasselt | Belgium | 3500 | |
8 | UZ Leuven Gasthuisberg | Leuven | Belgium | 3000 | |
9 | Tom Baker Cancer Centre | Calgary | Alberta | Canada | T2N 4N2 |
10 | Cross Cancer Institute | Edmonton | Alberta | Canada | T6G 1Z2 |
11 | Juravinski Cancer Centre | Hamilton | Ontario | Canada | L8V 5C2 |
12 | The Ottawa Hospital - General Campus | Ottawa | Ontario | Canada | K1H 8L6 |
13 | CIUSSS de l'Est-de-l'Île-de-Montréal Installation Hôpital Maisonneuve-Rosemont | Montreal | Quebec | Canada | H1T 2M4 |
14 | Jewish General Hospital | Montreal | Quebec | Canada | H3T 1E2 |
15 | Fakultni nemocnice Brno, Interni hematologicka a onkologicka klinika | Brno | Czechia | 625 00 | |
16 | Fakultni nemocnice Hradec Kralove | Hradec Kralove | Czechia | 500 05 | |
17 | Fakultni nemocnice Ostrava | Ostrava | Czechia | 708 52 | |
18 | Fakultni nemocnice Plzen, Hemato-onkologicke oddeleni | Plzen | Czechia | 323 00 | |
19 | Vseobecna fakultni nemocnice v Praze - I. interni klinika - klinika hematologie | Praha 2 | Czechia | 128 08 | |
20 | Aalborg University Hospital | Aalborg | Denmark | 9000 | |
21 | Aarhus Universitetshospital | Aarhus | Denmark | 8200 | |
22 | Rigshospitalet | Copenhagen | Denmark | 2100 | |
23 | Odense Universitetshospital | Odense C | Denmark | 5000 | |
24 | Roskilde Sygehus | Roskilde | Denmark | DK- 4000 | |
25 | CHU de Clermont-Ferrand | Clermont Ferrand | France | 63000 | |
26 | Hopital Claude Huriez | Lille | France | 59000 | |
27 | CHU Montpellier | Montpellier | France | 34295 | |
28 | Hopital Haut Leveque Service Maladie Du Sang | Pessac | France | 33604 | |
29 | Centre Hospitalier Universitaire de Reims, Hôpital Robert Debré | Reims | France | 51100 | |
30 | Institut Universitaire du Cancer Toulouse Oncopole | Toulouse Cedex 9 | France | 31059 | |
31 | CHU Bretonneau | Tours Cedex 9 | France | 37044 | |
32 | CHU-Nancy | Vandoeuvre les Nancy | France | 54511 | |
33 | Institut Gustave Roussy | Villejuif | France | 94805 | |
34 | Bnai Zion Medical Center | Haifa | Israel | 31048 | |
35 | Carmel Medical Center | Haifa | Israel | 34362 | |
36 | Hadassah Medical Center | Jerusalem | Israel | 9112001 | |
37 | Western Galilee Medical Center | Nahariya | Israel | 22100 | |
38 | Sheba Medical Center | Ramat Gan | Israel | 52621 | |
39 | Tel Aviv Sourasky Medical Center | Tel Aviv | Israel | 64239 | |
40 | Flevoziekenhuis | Almere | Netherlands | 1315RA | |
41 | OLVG | Amsterdam | Netherlands | 1091AC | |
42 | Academic Medical Center | Amsterdam | Netherlands | 1105 AZ | |
43 | Reinier de Graaf Gasthuis | Delft | Netherlands | 2625 AD | |
44 | MC Haaglanden | Den Haag | Netherlands | 2512 VA | |
45 | Albert Schweitzer Ziekenhuis | Dordrecht | Netherlands | 3318 AT | |
46 | Catharinaziekenhuis | Eindhoven | Netherlands | 5623 EJ | |
47 | Spaarne Gasthuis | Hoofddorp | Netherlands | 2134 TM | |
48 | Zuyderland Medical Center | Sittard-Geleen | Netherlands | 6162 BG | |
49 | Antonius hospital | Sneek | Netherlands | 8601 ZK | |
50 | Elisabeth zkh | Tilburg | Netherlands | 5022 GC | |
51 | Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich | Chorzów | Poland | 41-500 | |
52 | Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi | Lodz | Poland | 93-510 | |
53 | Samodzielny Publiczny Szpital Kliniczny Nr 1 | Lublin | Poland | 20-081 | |
54 | Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka, | Slupsk | Poland | 76-200 | |
55 | Instytut Hematologii i Transfuzjologii | Warszawa | Poland | 02-776 | |
56 | S.P. Botkin Moscow City Clinical Hospital | Moscow | Russian Federation | 125284 | |
57 | Nizhniy Novgorod Region Clinical Hospital | Nizhny Novgorod | Russian Federation | 603126 | |
58 | Ryazan Regional Clinical Hospital | Ryazan | Russian Federation | 390039 | |
59 | FSBIFederal Centre of Heart, Blood and Endocrinology named after V.A.Almazov MoH of the RF | Saint Petersburg | Russian Federation | 197341 | |
60 | St.-Petersburg Clinical Research Institute of Hematology and Transfusiology | St. Petersburg | Russian Federation | 193024 | |
61 | Hosp. Univ. Vall D Hebron | Barcelona | Spain | 08035 | |
62 | Hosp. Clinic I Provincial de Barcelona | Barcelona | Spain | 08036 | |
63 | Hosp. de La Santa Creu I Sant Pau | Barcelona | Spain | 8041 | |
64 | Hosp. Univ. de La Princesa | Madrid | Spain | 28006 | |
65 | Hosp. Gral. Univ. Gregorio Marañon | Madrid | Spain | 28007 | |
66 | Hosp. Univ. Infanta Leonor | Madrid | Spain | 28031 | |
67 | Hospital Ramon y Cajal | Madrid | Spain | 28034 | |
68 | Hosp. Univ. Fund. Jimenez Diaz | Madrid | Spain | 28040 | |
69 | Clinica Univ. de Navarra | Pamplona | Spain | 31008 | |
70 | Hospital Clinico Universitario Salamanca | Salamanca | Spain | 37007 | |
71 | Hosp. Virgen Del Rocio | Sevilla | Spain | 41013 | |
72 | Sunderby Sjukhus Medicinkliniken | Luelå | Sweden | 97180 | |
73 | Karolinska Universitetssjukhuset Solna, Centrum för Hematologi, Stockholm | Stockholm | Sweden | 171 76 | |
74 | Gazi Universitesi Tip FalKultesi | Ankara | Turkey | 06500 | |
75 | Ankara Universitesi Tip Fakültesi Ibn-i Sina Hastanesi | Ankara | Turkey | 6590 | |
76 | Ondokuz Mayis Universitesi Tip Fakultesi | Atakum | Turkey | 55270 | |
77 | V.K.V. Amerikan Hastanesi | Istanbul | Turkey | 34365 | |
78 | Dokuz Eylul Universitesi Tip Fakultesi | Izmir | Turkey | 35340 | |
79 | Birmingham Heartlands Hospital | Birmingham | United Kingdom | B9 5ST | |
80 | Addenbrookes Hospital | Cambridge | United Kingdom | CB2 0QQ | |
81 | Queen Mary University of London | Charterhouse Square | United Kingdom | EC1M 6BQ | |
82 | New Victoria Hospital | Glasgow | United Kingdom | G42 9LF | |
83 | St James's Hospital | Leeds | United Kingdom | LS9 7T | |
84 | Derriford Hospital | Plymouth | United Kingdom | PL6 8DH | |
85 | Barking Havering and Redbridge University Hospitals NHS Trust | Romford | United Kingdom | RM7 0AG | |
86 | Royal Hallamshire Hospital | Sheffield | United Kingdom | S10 2JF |
Sponsors and Collaborators
- Janssen Research & Development, LLC
- Pharmacyclics LLC.
Investigators
- Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Study Documents (Full-Text)
More Information
Publications
None provided.- CR108428
- 2017-004699-77
- 54179060CLL3011
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Treatment Arm A (Ibrutinib + Venetoclax) | Treatment Arm B (Chlorambucil + Obinutuzumab) |
---|---|---|
Arm/Group Description | 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. | 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. |
Period Title: Overall Study | ||
STARTED | 106 | 105 |
COMPLETED | 11 | 11 |
NOT COMPLETED | 95 | 94 |
Baseline Characteristics
Arm/Group Title | Treatment Arm A (Ibrutinib + Venetoclax) | Treatment Arm B (Chlorambucil + Obinutuzumab) | Total |
---|---|---|---|
Arm/Group Description | 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. | 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. | Total of all reporting groups |
Overall Participants | 106 | 105 | 211 |
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
71
(8.02)
|
72
(6.16)
|
71.5
(7.01)
|
Sex: Female, Male (Count of Participants) | |||
Female |
47
44.3%
|
42
40%
|
89
42.2%
|
Male |
59
55.7%
|
63
60%
|
122
57.8%
|
Ethnicity (NIH/OMB) (Count of Participants) | |||
Hispanic or Latino |
1
0.9%
|
3
2.9%
|
4
1.9%
|
Not Hispanic or Latino |
101
95.3%
|
99
94.3%
|
200
94.8%
|
Unknown or Not Reported |
4
3.8%
|
3
2.9%
|
7
3.3%
|
Race (NIH/OMB) (Count of Participants) | |||
American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
Asian |
0
0%
|
1
1%
|
1
0.5%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
Black or African American |
0
0%
|
0
0%
|
0
0%
|
White |
101
95.3%
|
101
96.2%
|
202
95.7%
|
More than one race |
1
0.9%
|
0
0%
|
1
0.5%
|
Unknown or Not Reported |
4
3.8%
|
3
2.9%
|
7
3.3%
|
Region of Enrollment (Count of Participants) | |||
BELGIUM |
7
6.6%
|
2
1.9%
|
9
4.3%
|
CANADA |
7
6.6%
|
10
9.5%
|
17
8.1%
|
CZECH REPUBLIC |
9
8.5%
|
13
12.4%
|
22
10.4%
|
DENMARK |
7
6.6%
|
5
4.8%
|
12
5.7%
|
FRANCE |
4
3.8%
|
3
2.9%
|
7
3.3%
|
ISRAEL |
6
5.7%
|
12
11.4%
|
18
8.5%
|
NETHERLANDS |
1
0.9%
|
6
5.7%
|
7
3.3%
|
POLAND |
12
11.3%
|
10
9.5%
|
22
10.4%
|
RUSSIAN FEDERATION |
23
21.7%
|
16
15.2%
|
39
18.5%
|
SPAIN |
10
9.4%
|
9
8.6%
|
19
9%
|
SWEDEN |
2
1.9%
|
0
0%
|
2
0.9%
|
TURKEY |
8
7.5%
|
13
12.4%
|
21
10%
|
UNITED KINGDOM |
8
7.5%
|
4
3.8%
|
12
5.7%
|
UNITED STATES |
2
1.9%
|
2
1.9%
|
4
1.9%
|
Outcome Measures
Title | Progression Free Survival (PFS) |
---|---|
Description | 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. |
Time Frame | Up to 2 years 10 months |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Treatment Arm A (Ibrutinib + Venetoclax) | Treatment Arm B (Chlorambucil + Obinutuzumab) |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 106 | 105 |
Median (95% Confidence Interval) [Months] |
NA
|
20.96
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Treatment Arm A (Ibrutinib + Venetoclax), Treatment Arm B (Chlorambucil + Obinutuzumab) |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | Log Rank | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.216 | |
Confidence Interval |
(2-Sided) 95% 0.131 to 0.357 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Minimal Residual Disease (MRD) Negative Rate |
---|---|
Description | 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. |
Time Frame | Up to 2 years 10 months |
Outcome Measure Data
Analysis Population Description |
---|
The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received. |
Arm/Group Title | Treatment Arm A (Ibrutinib + Venetoclax) | Treatment Arm B (Chlorambucil + Obinutuzumab) |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 106 | 105 |
Number (95% Confidence Interval) [Percentage of participants] |
55.7
52.5%
|
21.0
20%
|
Title | Complete Response Rate (CRR) |
---|---|
Description | 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. |
Time Frame | Up to 2 years 10 months |
Outcome Measure Data
Analysis Population Description |
---|
The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received. |
Arm/Group Title | Treatment Arm A (Ibrutinib + Venetoclax) | Treatment Arm B (Chlorambucil + Obinutuzumab) |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 106 | 105 |
Number (95% Confidence Interval) [Percentage of Participants] |
38.7
36.5%
|
11.4
10.9%
|
Title | Overall Response Rate (ORR) |
---|---|
Description | 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. |
Time Frame | Up to 2 years 10 months |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Treatment Arm A (Ibrutinib + Venetoclax) | Treatment Arm B (Chlorambucil + Obinutuzumab) |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 106 | 105 |
Number (95% Confidence Interval) [Percentage of participants] |
86.8
81.9%
|
84.8
80.8%
|
Title | Overall Survival (OS) |
---|---|
Description | OS is defined as the time from date of randomization to date of death from any cause. |
Time Frame | Up to 3 years 4 months |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Treatment Arm A (Ibrutinib + Venetoclax) | Treatment Arm B (Chlorambucil + Obinutuzumab) |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 11 | 16 |
Median (95% Confidence Interval) [Months] |
NA
|
NA
|
Title | Duration of Response (DOR) |
---|---|
Description | 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. |
Time Frame | Up to 2 years 10 months |
Outcome Measure Data
Analysis Population Description |
---|
Population analyzed included ITT amongst who were responders (PR or better). |
Arm/Group Title | Treatment Arm A (Ibrutinib + Venetoclax) | Treatment Arm B (Chlorambucil + Obinutuzumab) |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 92 | 89 |
Median (95% Confidence Interval) [Months] |
28.85
|
21.13
|
Title | Time-to-Next Treatment |
---|---|
Description | Time-to-next treatment was measured from the date of randomization to the start date of any subsequent anti-leukemic therapy. |
Time Frame | Up to 2 years 10 months |
Outcome Measure Data
Analysis Population Description |
---|
The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received. |
Arm/Group Title | Treatment Arm A (Ibrutinib + Venetoclax) | Treatment Arm B (Chlorambucil + Obinutuzumab) |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 106 | 105 |
Median (95% Confidence Interval) [Months] |
NA
|
NA
|
Title | Time to Worsening as Measured by Using EuroQol 5 Dimension 5 Level Questionnaire (EQ-5D-5L) |
---|---|
Description | 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). |
Time Frame | Up to 2 years 10 months |
Outcome Measure Data
Analysis Population Description |
---|
The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received. |
Arm/Group Title | Treatment Arm A (Ibrutinib + Venetoclax) | Treatment Arm B (Chlorambucil + Obinutuzumab) |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 106 | 105 |
EQ-5D-5L: Visual Analogue Score |
8.34
|
24.18
|
EQ-5D-5L: Utility Score |
14.29
|
24.11
|
Title | Time to Worsening Measured by European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC QLQ)-C30) |
---|---|
Description | 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). |
Time Frame | Up to 2 years 10 months |
Outcome Measure Data
Analysis Population Description |
---|
The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received. |
Arm/Group Title | Treatment Arm A (Ibrutinib + Venetoclax) | Treatment Arm B (Chlorambucil + Obinutuzumab) |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 106 | 105 |
Global Health Status |
14.95
|
24.18
|
Cognitive Functioning |
11.07
|
14.03
|
Emotional Functioning |
NA
|
25.00
|
Physical Functioning |
NA
|
NA
|
Role Functioning |
11.10
|
8.48
|
Social Functioning |
11.10
|
17.87
|
Fatigue (Symptom Scale) |
8.38
|
17.87
|
Nausea/Vomiting (Symptom Scale) |
11.07
|
NA
|
Pain (Symptom Scale) |
8.31
|
11.01
|
Title | Time to Worsening and Time to Improvement as Measured by Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score |
---|---|
Description | 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). |
Time Frame | Up to 2 years 10 months |
Outcome Measure Data
Analysis Population Description |
---|
The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received. |
Arm/Group Title | Treatment Arm A (Ibrutinib + Venetoclax) | Treatment Arm B (Chlorambucil + Obinutuzumab) |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 106 | 105 |
Time to Worsening |
8.15
|
14.03
|
Time to Improvement |
5.59
|
3.75
|
Title | Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability |
---|---|
Description | 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. |
Time Frame | Up to 3 years 4 months |
Outcome Measure Data
Analysis Population Description |
---|
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). |
Arm/Group Title | Treatment Arm A (Ibrutinib + Venetoclax) | Treatment Arm B (Chlorambucil + Obinutuzumab) |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 106 | 105 |
Count of Participants [Participants] |
105
99.1%
|
99
94.3%
|
Title | Number of Participants With Abnormal Clinical Laboratory Findings |
---|---|
Description | Number of participants with abnormal clinical laboratory findings (hematology and serum chemistry) were reported. |
Time Frame | Up to 2 years 10 months |
Outcome Measure Data
Analysis Population Description |
---|
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). |
Arm/Group Title | Treatment Arm A (Ibrutinib + Venetoclax) | Treatment Arm B (Chlorambucil + Obinutuzumab) |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 106 | 105 |
Hematology: Absolute Neutrophils Counts (Decrease) |
81
76.4%
|
95
90.5%
|
Hematology: Hemoglobin (Decrease) |
38
35.8%
|
42
40%
|
Hematology: Platelets (Decrease) |
52
49.1%
|
78
74.3%
|
Hematology: Any hemoglobin, platelet, or ANC decrease |
94
88.7%
|
103
98.1%
|
Chemistry: Alanine Transaminase (ALT) (Increase) |
22
20.8%
|
26
24.8%
|
Chemistry: Aspartate Aminotransferase (AST) (Increase) |
23
21.7%
|
30
28.6%
|
Chemistry: Alkaline Phosphatase (Increase) |
19
17.9%
|
21
20%
|
Chemistry: Bilirubin (Increase) |
36
34%
|
25
23.8%
|
Chemistry: Creatinine (Increase) |
33
31.1%
|
17
16.2%
|
Chemistry: Creatinine Clearance (Decrease) |
40
37.7%
|
17
16.2%
|
Chemistry: Hypercalcemia |
13
12.3%
|
3
2.9%
|
Chemistry: Hypoalbuminemia |
36
34%
|
20
19%
|
Chemistry: Hypocalcemia |
27
25.5%
|
30
28.6%
|
Chemistry: Phosphate (Decrease) |
16
15.1%
|
6
5.7%
|
Chemistry: Potassium (Decrease) |
25
23.6%
|
9
8.6%
|
Chemistry: Potassium (Increase) |
31
29.2%
|
22
21%
|
Chemistry: Sodium (Decrease) |
25
23.6%
|
26
24.8%
|
Chemistry: Sodium (Increase) |
12
11.3%
|
8
7.6%
|
Chemistry: Uric Acid (Increase) |
37
34.9%
|
19
18.1%
|
Title | Percentage of Participants With Sustained Hemoglobin Improvement |
---|---|
Description | 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. |
Time Frame | Up to 2 years 10 months |
Outcome Measure Data
Analysis Population Description |
---|
The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received. |
Arm/Group Title | Treatment Arm A (Ibrutinib + Venetoclax) | Treatment Arm B (Chlorambucil + Obinutuzumab) |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 106 | 105 |
Number [Percentage of Participants] |
44.3
41.8%
|
50.5
48.1%
|
Title | Percentage of Participants With Sustained Platelet Improvement |
---|---|
Description | 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. |
Time Frame | Up to 2 years 10 months |
Outcome Measure Data
Analysis Population Description |
---|
The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received. |
Arm/Group Title | Treatment Arm A (Ibrutinib + Venetoclax) | Treatment Arm B (Chlorambucil + Obinutuzumab) |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 106 | 105 |
Number [Percentage of Participants] |
24.5
23.1%
|
29.5
28.1%
|
Title | Plasma Concentration of Ibrutinib and Venetoclax |
---|---|
Description | Plasma concentrations of ibrutinib and venetoclax were determined by validated liquid chromatography-tandem mass spectrometry. |
Time Frame | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Treatment Arm A (Ibrutinib + Venetoclax) |
---|---|
Arm/Group Description | 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. |
Measure Participants | 79 |
Ibrutinib: Pre-dose Day 1 Cycle 2 (Ibrutinib Alone) |
5.70
(5.58)
|
Ibrutinib: Pre-dose Day 1 Cycle 3 (Ibrutinib Alone) |
6.20
(7.78)
|
Ibrutinib: Pre-dose Day 1 Cycle 5 (Ibrutinib and Venetoclax) |
6.37
(6.71)
|
Ibrutinib: Pre-dose Day 1 Cycle 6 (Ibrutinib and Venetoclax) |
5.90
(6.74)
|
Venetoclax: Pre-dose Day 1 Cycle 5 (Ibrutinib + Venetoclax) |
1139
(959)
|
Venetoclax: Pre-dose Day 1 Cycle 6 (Ibrutinib + Venetoclax) |
1765
(1573)
|
Adverse Events
Time Frame | Up to 3 years 4 months | |||
---|---|---|---|---|
Adverse Event Reporting Description | 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). | |||
Arm/Group Title | Treatment Arm A (Ibrutinib + Venetoclax) | Treatment Arm B (Chlorambucil + Obinutuzumab) | ||
Arm/Group Description | 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. | 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. | ||
All Cause Mortality |
||||
Treatment Arm A (Ibrutinib + Venetoclax) | Treatment Arm B (Chlorambucil + Obinutuzumab) | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 11/106 (10.4%) | 16/105 (15.2%) | ||
Serious Adverse Events |
||||
Treatment Arm A (Ibrutinib + Venetoclax) | Treatment Arm B (Chlorambucil + Obinutuzumab) | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 49/106 (46.2%) | 30/105 (28.6%) | ||
Blood and lymphatic system disorders | ||||
Anaemia | 3/106 (2.8%) | 2/105 (1.9%) | ||
Febrile Neutropenia | 1/106 (0.9%) | 3/105 (2.9%) | ||
Neutropenia | 2/106 (1.9%) | 1/105 (1%) | ||
Cardiac disorders | ||||
Acute Myocardial Infarction | 2/106 (1.9%) | 1/105 (1%) | ||
Angina Unstable | 1/106 (0.9%) | 0/105 (0%) | ||
Atrial Fibrillation | 7/106 (6.6%) | 0/105 (0%) | ||
Cardiac Arrest | 1/106 (0.9%) | 0/105 (0%) | ||
Cardiac Failure | 3/106 (2.8%) | 0/105 (0%) | ||
Cardiac Failure Congestive | 0/106 (0%) | 1/105 (1%) | ||
Myocardial Infarction | 1/106 (0.9%) | 0/105 (0%) | ||
Sinus Node Dysfunction | 2/106 (1.9%) | 0/105 (0%) | ||
Supraventricular Tachycardia | 0/106 (0%) | 1/105 (1%) | ||
Gastrointestinal disorders | ||||
Diarrhoea | 3/106 (2.8%) | 1/105 (1%) | ||
Gastritis | 1/106 (0.9%) | 0/105 (0%) | ||
Mesenteric Artery Thrombosis | 1/106 (0.9%) | 0/105 (0%) | ||
Oesophagitis | 0/106 (0%) | 1/105 (1%) | ||
General disorders | ||||
Asthenia | 1/106 (0.9%) | 0/105 (0%) | ||
Oedema Peripheral | 2/106 (1.9%) | 0/105 (0%) | ||
Pyrexia | 1/106 (0.9%) | 2/105 (1.9%) | ||
Sudden Death | 2/106 (1.9%) | 0/105 (0%) | ||
Hepatobiliary disorders | ||||
Cholecystitis Acute | 1/106 (0.9%) | 0/105 (0%) | ||
Cholecystitis Chronic | 1/106 (0.9%) | 0/105 (0%) | ||
Cholestasis | 0/106 (0%) | 1/105 (1%) | ||
Gallbladder Rupture | 0/106 (0%) | 1/105 (1%) | ||
Immune system disorders | ||||
Cytokine Release Syndrome | 0/106 (0%) | 1/105 (1%) | ||
Infections and infestations | ||||
Bronchitis | 1/106 (0.9%) | 0/105 (0%) | ||
Bronchopulmonary Aspergillosis | 1/106 (0.9%) | 0/105 (0%) | ||
Cellulitis | 1/106 (0.9%) | 0/105 (0%) | ||
Clostridium Colitis | 1/106 (0.9%) | 0/105 (0%) | ||
Covid-19 Pneumonia | 0/106 (0%) | 0/105 (0%) | ||
Erysipelas | 1/106 (0.9%) | 0/105 (0%) | ||
Escherichia Urinary Tract Infection | 0/106 (0%) | 1/105 (1%) | ||
Gastroenteritis | 1/106 (0.9%) | 0/105 (0%) | ||
Gastrointestinal Infection | 1/106 (0.9%) | 0/105 (0%) | ||
Infection | 1/106 (0.9%) | 0/105 (0%) | ||
Influenza | 1/106 (0.9%) | 0/105 (0%) | ||
Pneumococcal Sepsis | 0/106 (0%) | 1/105 (1%) | ||
Pneumonia | 6/106 (5.7%) | 6/105 (5.7%) | ||
Pneumonia Cytomegaloviral | 1/106 (0.9%) | 0/105 (0%) | ||
Respiratory Tract Infection | 0/106 (0%) | 1/105 (1%) | ||
Septic Shock | 1/106 (0.9%) | 0/105 (0%) | ||
Tonsillitis | 1/106 (0.9%) | 0/105 (0%) | ||
Urinary Tract Infection | 0/106 (0%) | 1/105 (1%) | ||
Injury, poisoning and procedural complications | ||||
Fall | 1/106 (0.9%) | 0/105 (0%) | ||
Femoral Neck Fracture | 1/106 (0.9%) | 0/105 (0%) | ||
Hip Fracture | 1/106 (0.9%) | 1/105 (1%) | ||
Infusion Related Reaction | 0/106 (0%) | 3/105 (2.9%) | ||
Multiple Injuries | 0/106 (0%) | 1/105 (1%) | ||
Overdose | 0/106 (0%) | 2/105 (1.9%) | ||
Spinal Compression Fracture | 1/106 (0.9%) | 0/105 (0%) | ||
Wound Necrosis | 1/106 (0.9%) | 0/105 (0%) | ||
Investigations | ||||
Alanine Aminotransferase Increased | 0/106 (0%) | 2/105 (1.9%) | ||
Aspartate Aminotransferase Increased | 0/106 (0%) | 1/105 (1%) | ||
Blood Phosphorus Increased | 0/106 (0%) | 1/105 (1%) | ||
Neutrophil Count Decreased | 1/106 (0.9%) | 0/105 (0%) | ||
Metabolism and nutrition disorders | ||||
Hyperkalaemia | 1/106 (0.9%) | 0/105 (0%) | ||
Hyperphosphataemia | 2/106 (1.9%) | 0/105 (0%) | ||
Iron Deficiency | 0/106 (0%) | 1/105 (1%) | ||
Tumour Lysis Syndrome | 0/106 (0%) | 3/105 (2.9%) | ||
Musculoskeletal and connective tissue disorders | ||||
Musculoskeletal Chest Pain | 1/106 (0.9%) | 0/105 (0%) | ||
Polyarthritis | 1/106 (0.9%) | 0/105 (0%) | ||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
Adenocarcinoma Gastric | 0/106 (0%) | 1/105 (1%) | ||
Hepatocellular Carcinoma | 1/106 (0.9%) | 0/105 (0%) | ||
Lung Neoplasm Malignant | 1/106 (0.9%) | 0/105 (0%) | ||
Myelodysplastic Syndrome | 0/106 (0%) | 1/105 (1%) | ||
Myeloproliferative Neoplasm | 0/106 (0%) | 1/105 (1%) | ||
Neoplasm Malignant | 1/106 (0.9%) | 0/105 (0%) | ||
Uterine Leiomyoma | 1/106 (0.9%) | 0/105 (0%) | ||
Nervous system disorders | ||||
Cerebral Haemorrhage | 1/106 (0.9%) | 0/105 (0%) | ||
Dizziness | 1/106 (0.9%) | 0/105 (0%) | ||
Ischaemic Stroke | 2/106 (1.9%) | 0/105 (0%) | ||
Spinal Cord Compression | 1/106 (0.9%) | 0/105 (0%) | ||
Toxic Encephalopathy | 1/106 (0.9%) | 0/105 (0%) | ||
Psychiatric disorders | ||||
Depression | 1/106 (0.9%) | 0/105 (0%) | ||
Major Depression | 1/106 (0.9%) | 0/105 (0%) | ||
Mental Disorder | 1/106 (0.9%) | 0/105 (0%) | ||
Renal and urinary disorders | ||||
Acute Kidney Injury | 1/106 (0.9%) | 0/105 (0%) | ||
Chronic Kidney Disease | 1/106 (0.9%) | 0/105 (0%) | ||
Haematuria | 2/106 (1.9%) | 0/105 (0%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Chronic Obstructive Pulmonary Disease | 1/106 (0.9%) | 0/105 (0%) | ||
Dyspnoea | 1/106 (0.9%) | 1/105 (1%) | ||
Dyspnoea Exertional | 1/106 (0.9%) | 0/105 (0%) | ||
Haemoptysis | 1/106 (0.9%) | 0/105 (0%) | ||
Pneumothorax | 1/106 (0.9%) | 0/105 (0%) | ||
Pulmonary Congestion | 1/106 (0.9%) | 0/105 (0%) | ||
Skin and subcutaneous tissue disorders | ||||
Dermatitis Bullous | 1/106 (0.9%) | 0/105 (0%) | ||
Ecchymosis | 1/106 (0.9%) | 0/105 (0%) | ||
Pyoderma Gangrenosum | 1/106 (0.9%) | 0/105 (0%) | ||
Rash | 1/106 (0.9%) | 0/105 (0%) | ||
Urticaria | 1/106 (0.9%) | 0/105 (0%) | ||
Vascular disorders | ||||
Hypertension | 1/106 (0.9%) | 0/105 (0%) | ||
Hypertensive Urgency | 1/106 (0.9%) | 0/105 (0%) | ||
Hypotension | 1/106 (0.9%) | 0/105 (0%) | ||
Venous Thrombosis | 1/106 (0.9%) | 0/105 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
Treatment Arm A (Ibrutinib + Venetoclax) | Treatment Arm B (Chlorambucil + Obinutuzumab) | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 98/106 (92.5%) | 98/105 (93.3%) | ||
Blood and lymphatic system disorders | ||||
Anaemia | 17/106 (16%) | 18/105 (17.1%) | ||
Leukopenia | 1/106 (0.9%) | 6/105 (5.7%) | ||
Neutropenia | 36/106 (34%) | 56/105 (53.3%) | ||
Thrombocytopenia | 12/106 (11.3%) | 28/105 (26.7%) | ||
Cardiac disorders | ||||
Atrial Fibrillation | 12/106 (11.3%) | 2/105 (1.9%) | ||
Palpitations | 6/106 (5.7%) | 3/105 (2.9%) | ||
Ear and labyrinth disorders | ||||
Vertigo | 8/106 (7.5%) | 0/105 (0%) | ||
Gastrointestinal disorders | ||||
Abdominal Pain | 2/106 (1.9%) | 5/105 (4.8%) | ||
Constipation | 11/106 (10.4%) | 7/105 (6.7%) | ||
Diarrhoea | 53/106 (50%) | 13/105 (12.4%) | ||
Dyspepsia | 10/106 (9.4%) | 3/105 (2.9%) | ||
Mouth Ulceration | 8/106 (7.5%) | 0/105 (0%) | ||
Nausea | 28/106 (26.4%) | 27/105 (25.7%) | ||
Vomiting | 15/106 (14.2%) | 14/105 (13.3%) | ||
General disorders | ||||
Asthenia | 9/106 (8.5%) | 7/105 (6.7%) | ||
Chills | 2/106 (1.9%) | 12/105 (11.4%) | ||
Fatigue | 16/106 (15.1%) | 10/105 (9.5%) | ||
Oedema Peripheral | 15/106 (14.2%) | 3/105 (2.9%) | ||
Pyrexia | 6/106 (5.7%) | 18/105 (17.1%) | ||
Infections and infestations | ||||
Bronchitis | 7/106 (6.6%) | 7/105 (6.7%) | ||
Conjunctivitis | 7/106 (6.6%) | 2/105 (1.9%) | ||
Nasopharyngitis | 4/106 (3.8%) | 7/105 (6.7%) | ||
Pharyngitis | 6/106 (5.7%) | 1/105 (1%) | ||
Pneumonia | 5/106 (4.7%) | 6/105 (5.7%) | ||
Upper Respiratory Tract Infection | 13/106 (12.3%) | 14/105 (13.3%) | ||
Urinary Tract Infection | 17/106 (16%) | 4/105 (3.8%) | ||
Injury, poisoning and procedural complications | ||||
Contusion | 5/106 (4.7%) | 0/105 (0%) | ||
Infusion Related Reaction | 0/106 (0%) | 28/105 (26.7%) | ||
Investigations | ||||
Alanine Aminotransferase Increased | 3/106 (2.8%) | 5/105 (4.8%) | ||
Aspartate Aminotransferase Increased | 3/106 (2.8%) | 6/105 (5.7%) | ||
Neutrophil Count Decreased | 10/106 (9.4%) | 9/105 (8.6%) | ||
Weight Decreased | 8/106 (7.5%) | 1/105 (1%) | ||
Metabolism and nutrition disorders | ||||
Decreased Appetite | 14/106 (13.2%) | 6/105 (5.7%) | ||
Hyperkalaemia | 8/106 (7.5%) | 5/105 (4.8%) | ||
Hyperphosphataemia | 9/106 (8.5%) | 0/105 (0%) | ||
Hyperuricaemia | 6/106 (5.7%) | 3/105 (2.9%) | ||
Hyponatraemia | 6/106 (5.7%) | 1/105 (1%) | ||
Musculoskeletal and connective tissue disorders | ||||
Arthralgia | 12/106 (11.3%) | 7/105 (6.7%) | ||
Back Pain | 10/106 (9.4%) | 7/105 (6.7%) | ||
Muscle Spasms | 9/106 (8.5%) | 2/105 (1.9%) | ||
Myalgia | 7/106 (6.6%) | 1/105 (1%) | ||
Pain in Extremity | 6/106 (5.7%) | 8/105 (7.6%) | ||
Nervous system disorders | ||||
Dizziness Postural | 4/106 (3.8%) | 6/105 (5.7%) | ||
Headache | 7/106 (6.6%) | 5/105 (4.8%) | ||
Psychiatric disorders | ||||
Insomnia | 9/106 (8.5%) | 5/105 (4.8%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Cough | 9/106 (8.5%) | 11/105 (10.5%) | ||
Dyspnoea | 6/106 (5.7%) | 8/105 (7.6%) | ||
Epistaxis | 12/106 (11.3%) | 3/105 (2.9%) | ||
Skin and subcutaneous tissue disorders | ||||
Hyperhidrosis | 1/106 (0.9%) | 6/105 (5.7%) | ||
Onychoclasis | 7/106 (6.6%) | 0/105 (0%) | ||
Pruritus | 8/106 (7.5%) | 5/105 (4.8%) | ||
Rash | 17/106 (16%) | 7/105 (6.7%) | ||
Vascular disorders | ||||
Haematoma | 8/106 (7.5%) | 2/105 (1.9%) | ||
Hypertension | 13/106 (12.3%) | 5/105 (4.8%) | ||
Hypotension | 3/106 (2.8%) | 10/105 (9.5%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
Name/Title | EXECUTIVE MEDICAL DIRECTOR |
---|---|
Organization | Janssen Research & Development, LLC |
Phone | 844-434-4210 |
ClinicalTrialDisclosure@its.jnj.com |
- CR108428
- 2017-004699-77
- 54179060CLL3011