Ibrutinib Plus Venetoclax in Subjects With Treatment-naive Chronic Lymphocytic Leukemia /Small Lymphocytic Lymphoma (CLL/SLL)
NCT ID: NCT02910583
Last Updated: 2024-12-20
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
323 participants
INTERVENTIONAL
2016-09-28
2024-03-27
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Allocation was not randomized for the Fixed Duration (FD) cohort.
Study Groups
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Fixed Duration (FD) Cohort: Open Label Ibrutinib + Venetoclax
Participants receive 420 mg of single-agent ibrutinib for first 3 cycles followed by ibrutinib plus venetoclax combination treatment (ibrutinib 420 mg and venetoclax 400 mg orally once daily on a continuous schedule) for 12 cycles (a cycle is defined by 28 days) or until disease progression or unacceptable toxicity.
ibrutinib
ibrutinib administered orally once daily (three 140 mg capsules)
venetoclax
venetoclax tablets will be administered orally once daily starting with a 5 week ramp up of 20 mg, 50 mg, 100 mg, 200 mg and 400 mg. After ramp up, venetoclax will be administered at 400 mg.
MRD Cohort/Confirmed Undetectable MRD (uMRD): Randomized to Ibrutinib (Blinded)
Participants receive 420 mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization (pre-randomization phase).
Participants with confirmed uMRD are randomized to receive ibrutinib 420 mg orally once daily on a continuous schedule until MRD-positive relapse, disease progression (PD), or unacceptable toxicity.
After MRD-positive relapse or disease progression (PD) by iwCLL criteria, participants can reintroduce 400 mg venetoclax with a 5-week ramp up. If venetoclax is to be reintroduced, venetoclax treatment is to continue at the dose of 400 mg/day for up to approximately 2 years (cumulative) until PD or unacceptable toxicity.
ibrutinib
ibrutinib administered orally once daily (three 140 mg capsules)
venetoclax
venetoclax tablets will be administered orally once daily starting with a 5 week ramp up of 20 mg, 50 mg, 100 mg, 200 mg and 400 mg. After ramp up, venetoclax will be administered at 400 mg.
MRD Cohort/Confirmed uMRD: Randomized Placebo (Blinded)
Participants receive 420 mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization (pre-randomization phase).
Participants with confirmed uMRD are randomized to receive placebo orally once daily on a continuous schedule until MRD-positive relapse, PD or unacceptable toxicity.
If MRD-positive relapse or PD is confirmed after restaging per iwCLL criteria, participants can first reintroduce oral daily ibrutinib with the option of subsequently reintroducing 400 mg venetoclax with a 5-week ramp up, if subsequent disease relapse per iwCLL criteria occurs after ibrutinib reintroduction. If venetoclax is to be reintroduced, venetoclax treatment is to continue at the dose of 400 mg/day for up to approximately 2 years (cumulative) until PD or unacceptable toxicity.
ibrutinib
ibrutinib administered orally once daily (three 140 mg capsules)
venetoclax
venetoclax tablets will be administered orally once daily starting with a 5 week ramp up of 20 mg, 50 mg, 100 mg, 200 mg and 400 mg. After ramp up, venetoclax will be administered at 400 mg.
Placebo
placebo capsules to match ibrutinib administered orally once daily
MRD Cohort/uMRD Not Confirmed: Randomized to Ibrutinib (Open-Label)
Participants receive 420 mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization (pre randomization phase).
Participants with uMRD not confirmed are randomized to receive open-label ibrutinib 420 mg orally once daily on a continuous schedule until PD or unacceptable toxicity.
In case of confirmed PD after restaging per iwCLL criteria, participants can continue ibrutinib and reintroduce venetoclax treatment. If venetoclax is to be reintroduced, venetoclax treatment is to continue at the dose of 400 mg/day for up to approximately 2 years (cumulative) until PD or unacceptable toxicity.
ibrutinib
ibrutinib administered orally once daily (three 140 mg capsules)
venetoclax
venetoclax tablets will be administered orally once daily starting with a 5 week ramp up of 20 mg, 50 mg, 100 mg, 200 mg and 400 mg. After ramp up, venetoclax will be administered at 400 mg.
MRD Cohort/uMRD Not Confirmed: Randomized Ibrutinib + Venetoclax (Open-Label)
Participants receive 420 mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization (pre randomization phase).
Participants with uMRD not confirmed are randomized to receive open-label ibrutinib 420 mg and venetoclax 400 mg orally once daily on a continuous schedule until PD or unacceptable toxicity. Venetoclax was allowed for administration up to 2 years cumulatively from first dose started in the pre-randomization phase to last dose in the randomization phase.
ibrutinib
ibrutinib administered orally once daily (three 140 mg capsules)
venetoclax
venetoclax tablets will be administered orally once daily starting with a 5 week ramp up of 20 mg, 50 mg, 100 mg, 200 mg and 400 mg. After ramp up, venetoclax will be administered at 400 mg.
Interventions
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ibrutinib
ibrutinib administered orally once daily (three 140 mg capsules)
venetoclax
venetoclax tablets will be administered orally once daily starting with a 5 week ramp up of 20 mg, 50 mg, 100 mg, 200 mg and 400 mg. After ramp up, venetoclax will be administered at 400 mg.
Placebo
placebo capsules to match ibrutinib administered orally once daily
Eligibility Criteria
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Inclusion Criteria
* Measurable nodal disease by computed tomography (CT)
* Adequate hepatic, and renal function
* Adequate hematologic function
* absolute neutrophil count \>750/µL
* platelet count \>30,000 /μL
* hemoglobin \>8.0 g/dL
Exclusion Criteria
* Known allergy to xanthine oxidase inhibitors and/or rasburicase for subjects at risk for tumor lysis syndrome (TLS)
18 Years
70 Years
ALL
No
Sponsors
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Janssen Research & Development, LLC
INDUSTRY
Pharmacyclics LLC.
INDUSTRY
Responsible Party
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Principal Investigators
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ABBVIE INC.
Role: STUDY_DIRECTOR
AbbVie
Locations
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City of Hope /ID# 1142-0047
Duarte, California, United States
Moores Cancer Center at UC San Diego /ID# 1142-0241
La Jolla, California, United States
UC Irvine Medical Center - Chao Family Comprehensive Cancer Center /ID# 1142-0008
Orange, California, United States
Norton Cancer Center /ID# 1142-0071
Louisville, Kentucky, United States
Rutgers Cancer Institute of New Jersey /ID# 1142-1193
New Brunswick, New Jersey, United States
Northwell Health/Long Island Jewish Hospital /ID# 1142-0350
New Hyde Park, New York, United States
New York Presbyterian Hospital/Weill Cornell Med College /ID# 1142-0200
New York, New York, United States
University of Rochester Cancer Center /ID# 1142-0127
Rochester, New York, United States
Charlotte-Mecklenberg Hospital, Carolinas Healthcare System, Levine Cancer Inst /ID# 1142-0733
Charlotte, North Carolina, United States
Cleveland Clinic Foundation /ID# 1142-0739
Cleveland, Ohio, United States
University of Pennsylvania /ID# 1142-0069
Philadelphia, Pennsylvania, United States
Tennessee Oncology - Chattanooga /ID# 1142-0123
Chattanooga, Tennessee, United States
MD Anderson Cancer Center /ID# 1142-0032
Houston, Texas, United States
Swedish Cancer Institute /ID# 1142-0114
Seattle, Washington, United States
St George Hospital /ID# 1142-0654
Kogarah, New South Wales, Australia
Flinders Medical Centre /ID# 1142-0163
Bedford Park, South Australia, Australia
Monash Medical Centre /ID# 1142-0556
Clayton, Victoria, Australia
Peter MacCallum Cancer Centre-East Melbourne /ID# 1142-0633
East Melbourne, Victoria, Australia
St Vincent's Hospital Melbourne /ID# 1142-0501
Fitzroy, Victoria, Australia
Frankston Hospital /ID# 1142-0715
Frankston, Victoria, Australia
Austin Health /ID# 1142-0170
Heidelberg, Victoria, Australia
Ospedale San Raffaele IRCCS /ID# 1142-0523
Milan, Lombardy, Italy
Ospedale Policlinico San Martino /ID# 1142-0903
Genova, , Italy
ASST Grande Ospedale Metropolitano Niguarda /ID# 1142-0581
Milan, , Italy
Azienda Ospedaliero-Universitaria di Modena /ID# 1142-0524
Modena, , Italy
Azienda Ospedaliero Universitaria Maggiore della Carita di Novara /ID# 1142-0582
Novara, , Italy
Azienda Ospedaliera di Padova /ID# 1142-1175
Padua, , Italy
Azienda USL di Piacenza - Ospedale Guglielmo da Saliceto /ID# 1142-1182
Piacenza, , Italy
Middlemore Hospital /ID# 1142-0662
Otahuhu, Auckland, New Zealand
Christchurch Hospital /ID# 1142-0589
Christchurch, Canterbury, New Zealand
Palmerston North Hospital /ID# 1142-0585
Palmerston North, Manawatu-Wanganui, New Zealand
North Shore Hospital /ID# 1142-0663
Auckland, , New Zealand
Malopolskie Centrum Medyczne /ID# 1142-0364
Krakow, Lesser Poland Voivodeship, Poland
Duplicate_Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie /ID# 1142-0590
Lublin, Lublin Voivodeship, Poland
Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. ks. B. /ID# 1142-0592
Brzozów, Podkarpackie Voivodeship, Poland
Samodzielny Publiczny Szpital Klinczny Nr-1- Akademickie Cenrum Klinic /ID# 1142-0529
Gdansk, Pomeranian Voivodeship, Poland
Medical Univ. of Lodz and Copernicus Memorial Hospital /ID# 1142-0531
Lodz, , Poland
Hospital Duran i Reynals /ID# 1142-0604
L'Hospitalet de Llobregat, Barcelona, Spain
Hospital Universitario Puerta de Hierro, Majadahonda /ID# 1142-0536
Majadahonda, Madrid, Spain
Complejo Hospitalario de Navarra /ID# 1142-1197
Pamplona, Navarre, Spain
Hospital Clinic de Barcelona /ID# 1142-0533
Barcelona, , Spain
Hospital Santa Creu i Sant Pau /ID# 1142-0535
Barcelona, , Spain
Hospital Universitario Virgen de las Nieves /ID# 1142-1196
Granada, , Spain
Hospital Universitario Ramon y Cajal /ID# 1142-0874
Madrid, , Spain
Hospital Universitario 12 de Octubre /ID# 1142-0864
Madrid, , Spain
Hospital Clinico Universitario de Salamanca /ID# 1142-0790
Salamanca, , Spain
Countries
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References
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Moreno C, Solman IG, Tam CS, Grigg A, Scarfo L, Kipps TJ, Srinivasan S, Mali RS, Zhou C, Dean JP, Szafer-Glusman E, Choi M. Immune restoration with ibrutinib plus venetoclax in first-line chronic lymphocytic leukemia: the phase 2 CAPTIVATE study. Blood Adv. 2023 Sep 26;7(18):5294-5303. doi: 10.1182/bloodadvances.2023010236.
Wierda WG, Allan JN, Siddiqi T, Kipps TJ, Opat S, Tedeschi A, Badoux XC, Kuss BJ, Jackson S, Moreno C, Jacobs R, Pagel JM, Flinn I, Pak Y, Zhou C, Szafer-Glusman E, Ninomoto J, Dean JP, James DF, Ghia P, Tam CS. Ibrutinib Plus Venetoclax for First-Line Treatment of Chronic Lymphocytic Leukemia: Primary Analysis Results From the Minimal Residual Disease Cohort of the Randomized Phase II CAPTIVATE Study. J Clin Oncol. 2021 Dec 1;39(34):3853-3865. doi: 10.1200/JCO.21.00807. Epub 2021 Oct 7.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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2016-002293-12
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
PCYC-1142-CA
Identifier Type: -
Identifier Source: org_study_id