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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) (GLOW)

Primary Purpose

Leukemia, Lymphocytic, Chronic, B-Cell

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Ibrutinib
Venetoclax
Chlorambucil
Obinutuzumab
Ibrutinib (as Subsequent Therapy)
Sponsored by
Janssen Research & Development, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia, Lymphocytic, Chronic, B-Cell

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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:

    1. Cumulative Illness Rating Scale (CIRS) score > 6
    2. 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

Sites / Locations

  • Norton Cancer Institute
  • John Theurer Cancer Center
  • Novant Health
  • Institut - Jules Bordet
  • ZNA Stuivenberg
  • Universitair Ziekenhuis Gent
  • Virga Jessa Ziekenhuis
  • UZ Leuven Gasthuisberg
  • Tom Baker Cancer Centre
  • Cross Cancer Institute
  • Juravinski Cancer Centre
  • The Ottawa Hospital - General Campus
  • CIUSSS de l'Est-de-l'Île-de-Montréal Installation Hôpital Maisonneuve-Rosemont
  • Jewish General Hospital
  • Fakultni nemocnice Brno, Interni hematologicka a onkologicka klinika
  • Fakultni nemocnice Hradec Kralove
  • Fakultni nemocnice Ostrava
  • Fakultni nemocnice Plzen, Hemato-onkologicke oddeleni
  • Vseobecna fakultni nemocnice v Praze - I. interni klinika - klinika hematologie
  • Aalborg University Hospital
  • Aarhus Universitetshospital
  • Rigshospitalet
  • Odense Universitetshospital
  • Roskilde Sygehus
  • CHU de Clermont-Ferrand
  • Hopital Claude Huriez
  • CHU Montpellier
  • Hopital Haut Leveque Service Maladie Du Sang
  • Centre Hospitalier Universitaire de Reims, Hôpital Robert Debré
  • Institut Universitaire du Cancer Toulouse Oncopole
  • CHU Bretonneau
  • CHU-Nancy
  • Institut Gustave Roussy
  • Bnai Zion Medical Center
  • Carmel Medical Center
  • Hadassah Medical Center
  • Western Galilee Medical Center
  • Sheba Medical Center
  • Tel Aviv Sourasky Medical Center
  • Flevoziekenhuis
  • OLVG
  • Academic Medical Center
  • Reinier de Graaf Gasthuis
  • MC Haaglanden
  • Albert Schweitzer Ziekenhuis
  • Catharinaziekenhuis
  • Spaarne Gasthuis
  • Zuyderland Medical Center
  • Antonius hospital
  • Elisabeth zkh
  • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich
  • Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi
  • Samodzielny Publiczny Szpital Kliniczny Nr 1
  • Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka,
  • Instytut Hematologii i Transfuzjologii
  • S.P. Botkin Moscow City Clinical Hospital
  • Nizhniy Novgorod Region Clinical Hospital
  • Ryazan Regional Clinical Hospital
  • FSBIFederal Centre of Heart, Blood and Endocrinology named after V.A.Almazov MoH of the RF
  • St.-Petersburg Clinical Research Institute of Hematology and Transfusiology
  • Hosp. Univ. Vall D Hebron
  • Hosp. Clinic I Provincial de Barcelona
  • Hosp. de La Santa Creu I Sant Pau
  • Hosp. Univ. de La Princesa
  • Hosp. Gral. Univ. Gregorio Maranon
  • Hosp. Univ. Infanta Leonor
  • Hospital Ramon y Cajal
  • Hosp. Univ. Fund. Jimenez Diaz
  • Clinica Univ. de Navarra
  • Hospital Clinico Universitario Salamanca
  • Hosp. Virgen Del Rocio
  • Sunderby Sjukhus Medicinkliniken
  • Karolinska Universitetssjukhuset Solna, Centrum för Hematologi, Stockholm
  • Gazi Universitesi Tip FalKultesi
  • Ankara Universitesi Tip Fakültesi Ibn-i Sina Hastanesi
  • Ondokuz Mayis Universitesi Tip Fakultesi
  • V.K.V. Amerikan Hastanesi
  • Dokuz Eylul Universitesi Tip Fakultesi
  • Birmingham Heartlands Hospital
  • Addenbrookes Hospital
  • Queen Mary University of London
  • New Victoria Hospital
  • St James's Hospital
  • Derriford Hospital
  • Barking Havering and Redbridge University Hospitals NHS Trust
  • Royal Hallamshire Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Treatment Arm A: Ibrutinib and Venetoclax (I+VEN)

Treatment Arm B: Chlorambucil and Obinutuzumab (G-Clb)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
Overall Survival (OS)
OS is defined as the time from date of randomization to date of death from any cause.
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.
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.
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).
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).
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).
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.
Number of Participants With Abnormal Clinical Laboratory Findings
Number of participants with abnormal clinical laboratory findings (hematology and serum chemistry) were reported.
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.
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.
Plasma Concentration of Ibrutinib and Venetoclax
Plasma concentrations of ibrutinib and venetoclax were determined by validated liquid chromatography-tandem mass spectrometry.

Full Information

First Posted
March 6, 2018
Last Updated
October 10, 2023
Sponsor
Janssen Research & Development, LLC
Collaborators
Pharmacyclics LLC.
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1. Study Identification

Unique Protocol Identification Number
NCT03462719
Brief Title
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)
Acronym
GLOW
Official Title
A Randomized, Open-label, Phase 3 Study of the Combination of Ibrutinib Plus Venetoclax Versus Chlorambucil Plus Obinutuzumab for the First-line Treatment of Subjects With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL).
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 17, 2018 (Actual)
Primary Completion Date
February 26, 2021 (Actual)
Study Completion Date
April 5, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
Collaborators
Pharmacyclics LLC.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphocytic, Chronic, B-Cell

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
211 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment Arm A: Ibrutinib and Venetoclax (I+VEN)
Arm Type
Experimental
Arm Description
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.
Arm Title
Treatment Arm B: Chlorambucil and Obinutuzumab (G-Clb)
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ibrutinib
Intervention Description
Participants will receive ibrutinib 420 mg orally once daily up to 15 cycles.
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Chlorambucil
Intervention Description
Participants will receive chlorambucil at a dose of 0.5 mg/kg body weight on Days 1 and 15 of Cycles 1 to 6.
Intervention Type
Drug
Intervention Name(s)
Obinutuzumab
Intervention Description
Participant will receive obinutuzumab 1000 mg intravenously on Days 1, 8, and 15 of Cycle 1, and Day 1 of Cycles 2 to 6.
Intervention Type
Drug
Intervention Name(s)
Ibrutinib (as Subsequent Therapy)
Intervention Description
Participants will receive ibrutinib 420 mg orally once daily until disease progression or unacceptable toxicity during the subsequent therapy phase.
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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
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
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
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 4 years 10 months
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
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
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
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
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
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 4 years 10 months
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 4 years 10 months
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
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
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
Facility Name
Norton Cancer Institute
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40207
Country
United States
Facility Name
John Theurer Cancer Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Novant Health
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Institut - Jules Bordet
City
Anderlecht
ZIP/Postal Code
1070
Country
Belgium
Facility Name
ZNA Stuivenberg
City
Antwerpen
ZIP/Postal Code
2060
Country
Belgium
Facility Name
Universitair Ziekenhuis Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Virga Jessa Ziekenhuis
City
Hasselt
ZIP/Postal Code
3500
Country
Belgium
Facility Name
UZ Leuven Gasthuisberg
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Tom Baker Cancer Centre
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Facility Name
Cross Cancer Institute
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
Juravinski Cancer Centre
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 5C2
Country
Canada
Facility Name
The Ottawa Hospital - General Campus
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
CIUSSS de l'Est-de-l'Île-de-Montréal Installation Hôpital Maisonneuve-Rosemont
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
Facility Name
Jewish General Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Facility Name
Fakultni nemocnice Brno, Interni hematologicka a onkologicka klinika
City
Brno
ZIP/Postal Code
625 00
Country
Czechia
Facility Name
Fakultni nemocnice Hradec Kralove
City
Hradec Kralove
ZIP/Postal Code
500 05
Country
Czechia
Facility Name
Fakultni nemocnice Ostrava
City
Ostrava
ZIP/Postal Code
708 52
Country
Czechia
Facility Name
Fakultni nemocnice Plzen, Hemato-onkologicke oddeleni
City
Plzen
ZIP/Postal Code
323 00
Country
Czechia
Facility Name
Vseobecna fakultni nemocnice v Praze - I. interni klinika - klinika hematologie
City
Praha 2
ZIP/Postal Code
128 08
Country
Czechia
Facility Name
Aalborg University Hospital
City
Aalborg
ZIP/Postal Code
9000
Country
Denmark
Facility Name
Aarhus Universitetshospital
City
Aarhus
ZIP/Postal Code
8200
Country
Denmark
Facility Name
Rigshospitalet
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Odense Universitetshospital
City
Odense C
ZIP/Postal Code
5000
Country
Denmark
Facility Name
Roskilde Sygehus
City
Roskilde
ZIP/Postal Code
DK- 4000
Country
Denmark
Facility Name
CHU de Clermont-Ferrand
City
Clermont Ferrand
ZIP/Postal Code
63000
Country
France
Facility Name
Hopital Claude Huriez
City
Lille
ZIP/Postal Code
59000
Country
France
Facility Name
CHU Montpellier
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
Hopital Haut Leveque Service Maladie Du Sang
City
Pessac
ZIP/Postal Code
33604
Country
France
Facility Name
Centre Hospitalier Universitaire de Reims, Hôpital Robert Debré
City
Reims
ZIP/Postal Code
51100
Country
France
Facility Name
Institut Universitaire du Cancer Toulouse Oncopole
City
Toulouse Cedex 9
ZIP/Postal Code
31059
Country
France
Facility Name
CHU Bretonneau
City
Tours Cedex 9
ZIP/Postal Code
37044
Country
France
Facility Name
CHU-Nancy
City
Vandoeuvre les Nancy
ZIP/Postal Code
54511
Country
France
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
94805
Country
France
Facility Name
Bnai Zion Medical Center
City
Haifa
ZIP/Postal Code
31048
Country
Israel
Facility Name
Carmel Medical Center
City
Haifa
ZIP/Postal Code
34362
Country
Israel
Facility Name
Hadassah Medical Center
City
Jerusalem
ZIP/Postal Code
9112001
Country
Israel
Facility Name
Western Galilee Medical Center
City
Nahariya
ZIP/Postal Code
22100
Country
Israel
Facility Name
Sheba Medical Center
City
Ramat Gan
ZIP/Postal Code
52621
Country
Israel
Facility Name
Tel Aviv Sourasky Medical Center
City
Tel Aviv
ZIP/Postal Code
64239
Country
Israel
Facility Name
Flevoziekenhuis
City
Almere
ZIP/Postal Code
1315RA
Country
Netherlands
Facility Name
OLVG
City
Amsterdam
ZIP/Postal Code
1091AC
Country
Netherlands
Facility Name
Academic Medical Center
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
Reinier de Graaf Gasthuis
City
Delft
ZIP/Postal Code
2625 AD
Country
Netherlands
Facility Name
MC Haaglanden
City
Den Haag
ZIP/Postal Code
2512 VA
Country
Netherlands
Facility Name
Albert Schweitzer Ziekenhuis
City
Dordrecht
ZIP/Postal Code
3318 AT
Country
Netherlands
Facility Name
Catharinaziekenhuis
City
Eindhoven
ZIP/Postal Code
5623 EJ
Country
Netherlands
Facility Name
Spaarne Gasthuis
City
Hoofddorp
ZIP/Postal Code
2134 TM
Country
Netherlands
Facility Name
Zuyderland Medical Center
City
Sittard-Geleen
ZIP/Postal Code
6162 BG
Country
Netherlands
Facility Name
Antonius hospital
City
Sneek
ZIP/Postal Code
8601 ZK
Country
Netherlands
Facility Name
Elisabeth zkh
City
Tilburg
ZIP/Postal Code
5022 GC
Country
Netherlands
Facility Name
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich
City
Chorzów
ZIP/Postal Code
41-500
Country
Poland
Facility Name
Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi
City
Lodz
ZIP/Postal Code
93-510
Country
Poland
Facility Name
Samodzielny Publiczny Szpital Kliniczny Nr 1
City
Lublin
ZIP/Postal Code
20-081
Country
Poland
Facility Name
Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka,
City
Slupsk
ZIP/Postal Code
76-200
Country
Poland
Facility Name
Instytut Hematologii i Transfuzjologii
City
Warszawa
ZIP/Postal Code
02-776
Country
Poland
Facility Name
S.P. Botkin Moscow City Clinical Hospital
City
Moscow
ZIP/Postal Code
125284
Country
Russian Federation
Facility Name
Nizhniy Novgorod Region Clinical Hospital
City
Nizhny Novgorod
ZIP/Postal Code
603126
Country
Russian Federation
Facility Name
Ryazan Regional Clinical Hospital
City
Ryazan
ZIP/Postal Code
390039
Country
Russian Federation
Facility Name
FSBIFederal Centre of Heart, Blood and Endocrinology named after V.A.Almazov MoH of the RF
City
Saint Petersburg
ZIP/Postal Code
197341
Country
Russian Federation
Facility Name
St.-Petersburg Clinical Research Institute of Hematology and Transfusiology
City
St. Petersburg
ZIP/Postal Code
193024
Country
Russian Federation
Facility Name
Hosp. Univ. Vall D Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hosp. Clinic I Provincial de Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hosp. de La Santa Creu I Sant Pau
City
Barcelona
ZIP/Postal Code
8041
Country
Spain
Facility Name
Hosp. Univ. de La Princesa
City
Madrid
ZIP/Postal Code
28006
Country
Spain
Facility Name
Hosp. Gral. Univ. Gregorio Maranon
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Hosp. Univ. Infanta Leonor
City
Madrid
ZIP/Postal Code
28031
Country
Spain
Facility Name
Hospital Ramon y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Hosp. Univ. Fund. Jimenez Diaz
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Clinica Univ. de Navarra
City
Pamplona
ZIP/Postal Code
31008
Country
Spain
Facility Name
Hospital Clinico Universitario Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Facility Name
Hosp. Virgen Del Rocio
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Sunderby Sjukhus Medicinkliniken
City
Luelå
ZIP/Postal Code
97180
Country
Sweden
Facility Name
Karolinska Universitetssjukhuset Solna, Centrum för Hematologi, Stockholm
City
Stockholm
ZIP/Postal Code
171 76
Country
Sweden
Facility Name
Gazi Universitesi Tip FalKultesi
City
Ankara
ZIP/Postal Code
06500
Country
Turkey
Facility Name
Ankara Universitesi Tip Fakültesi Ibn-i Sina Hastanesi
City
Ankara
ZIP/Postal Code
6590
Country
Turkey
Facility Name
Ondokuz Mayis Universitesi Tip Fakultesi
City
Atakum
ZIP/Postal Code
55270
Country
Turkey
Facility Name
V.K.V. Amerikan Hastanesi
City
Istanbul
ZIP/Postal Code
34365
Country
Turkey
Facility Name
Dokuz Eylul Universitesi Tip Fakultesi
City
Izmir
ZIP/Postal Code
35340
Country
Turkey
Facility Name
Birmingham Heartlands Hospital
City
Birmingham
ZIP/Postal Code
B9 5ST
Country
United Kingdom
Facility Name
Addenbrookes Hospital
City
Cambridge
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
Facility Name
Queen Mary University of London
City
Charterhouse Square
ZIP/Postal Code
EC1M 6BQ
Country
United Kingdom
Facility Name
New Victoria Hospital
City
Glasgow
ZIP/Postal Code
G42 9LF
Country
United Kingdom
Facility Name
St James's Hospital
City
Leeds
ZIP/Postal Code
LS9 7T
Country
United Kingdom
Facility Name
Derriford Hospital
City
Plymouth
ZIP/Postal Code
PL6 8DH
Country
United Kingdom
Facility Name
Barking Havering and Redbridge University Hospitals NHS Trust
City
Romford
ZIP/Postal Code
RM7 0AG
Country
United Kingdom
Facility Name
Royal Hallamshire Hospital
City
Sheffield
ZIP/Postal Code
S10 2JF
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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)

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