Ibrutinib Plus Venetoclax in Subjects With Treatment-naive Chronic Lymphocytic Leukemia /Small Lymphocytic Lymphoma (CLL/SLL)

NCT02910583 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: PCYC-1142-CA2016-002293-12
• Study Type: interventional
• Target: 323
• Locations: 6 countries
• Sites: 46

Brief Summary

This is a multicenter, 2-cohort Phase 2 study assessing both minimal residual disease (MRD)-guided discontinuation and fixed duration therapy with the combination of ibrutinib + venetoclax in subjects with treatment-naïve CLL or SLL.

Conditions

Leukemia; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (2)

• MRD Cohort: 1-Year Disease-Free Survival (DFS) Rate in Confirmed uMRD Randomized Participants

  DFS is defined as time from randomization date to MRD-positive relapse, or disease progression per investigator assessment (per 2008 International Workshop for Chronic Lymphocytic Leukemia \[IWCLL\] criteria \[Halleck et al\]) or death from any cause, whichever occurred first. 1-year DFS estimated using Kaplan-Meier method at 12 months landmark time.

  1 year after randomization

• FD Cohort: Complete Response Rate (CRR; Complete Response/Complete Response With Incomplete Blood Count Recovery [CR/CRi]) Rate

  CR/CRi rate is defined as the percentage of participants achieving a best overall response of complete response (CR), CR with incomplete blood count recovery (CRi) per 2008 IWCLL criteria (halleck et al.) on or prior to initiation of subsequent antineoplastic therapy or, if applicable, reintroduction of study treatment, whichever occurred earlier.

  From the first dose of ibrutinib to the first confirmed PD, for a median follow-up of 69.0 months.

Secondary Outcomes (24)

• MRD Cohort: CRR (CR/CRi Rate)

  From the first dose of ibrutinib to the first confirmed PD, for an overall median follow-up of 67.0 months. (Median follow up duration for the individual MRD Cohort treatment arms listed above.)

• MRD Cohort: Overall Response Rate (ORR)

  From the first dose of ibrutinib to the first confirmed PD, for an overall median follow-up of 67.0 months. (Median follow up duration for the individual MRD Cohort treatment arms listed above.)

• MRD Cohort: Duration of Response (DOR) at 42 Months Landmark Time

  From initial documentation of a response until PD or death from any cause, whichever occurs first, for an overall median follow-up of 67.0 months. (Median follow up duration for the individual MRD Cohort treatment arms listed above.)

• MRD Cohort: MRD-Negativity Rate

  From randomization date until before any subsequent antineoplastic therapy, for an overall median follow-up of 67.0 months. (Median follow up duration for the individual MRD Cohort treatment arms listed above.)

• MRD Cohort: Tumor Lysis Syndrome (TLS) Risk Reduction Rate With 3-Cycle Ibrutinib Lead-In (Percentage of Participants No Longer High Risk After 3-cycle Lead-in)

  Baseline, and last post-baseline value on or prior to venetoclax first dose date (cycle 4 day 1) or, for participants who never received venetoclax, the post-baseline value closest to cycle 4 day 1 (i.e. 84 days after the first dose date of ibrutinib).

Study Arms (5)

Fixed Duration (FD) Cohort: Open Label Ibrutinib + Venetoclax

EXPERIMENTAL

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.

Drug: ibrutinib; Drug: venetoclax

MRD Cohort/Confirmed Undetectable MRD (uMRD): Randomized to Ibrutinib (Blinded)

EXPERIMENTAL

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.

Drug: ibrutinib; Drug: venetoclax

MRD Cohort/Confirmed uMRD: Randomized Placebo (Blinded)

PLACEBO COMPARATOR

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.

Drug: ibrutinib; Drug: venetoclax; Drug: Placebo

MRD Cohort/uMRD Not Confirmed: Randomized to Ibrutinib (Open-Label)

EXPERIMENTAL

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.

Drug: ibrutinib; Drug: venetoclax

MRD Cohort/uMRD Not Confirmed: Randomized Ibrutinib + Venetoclax (Open-Label)

EXPERIMENTAL

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.

Drug: ibrutinib; Drug: venetoclax

Interventions

ibrutinib DRUG

ibrutinib administered orally once daily (three 140 mg capsules)

Fixed Duration (FD) Cohort: Open Label Ibrutinib + Venetoclax; MRD Cohort/Confirmed Undetectable MRD (uMRD): Randomized to Ibrutinib (Blinded); MRD Cohort/Confirmed uMRD: Randomized Placebo (Blinded); MRD Cohort/uMRD Not Confirmed: Randomized Ibrutinib + Venetoclax (Open-Label); MRD Cohort/uMRD Not Confirmed: Randomized to Ibrutinib (Open-Label)

venetoclax DRUG

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.

Fixed Duration (FD) Cohort: Open Label Ibrutinib + Venetoclax; MRD Cohort/Confirmed Undetectable MRD (uMRD): Randomized to Ibrutinib (Blinded); MRD Cohort/Confirmed uMRD: Randomized Placebo (Blinded); MRD Cohort/uMRD Not Confirmed: Randomized Ibrutinib + Venetoclax (Open-Label); MRD Cohort/uMRD Not Confirmed: Randomized to Ibrutinib (Open-Label)

Placebo DRUG

placebo capsules to match ibrutinib administered orally once daily

MRD Cohort/Confirmed uMRD: Randomized Placebo (Blinded)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of CLL/SLL that meets 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) diagnostic criteria (Hallek et al), with active disease meeting at least 1 IWCLL criteria for requiring treatment.
• 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

You may not qualify if:

• Any prior therapy used for treatment of CLL/SLL
• Known allergy to xanthine oxidase inhibitors and/or rasburicase for subjects at risk for tumor lysis syndrome (TLS)

Sponsors & Collaborators

• Pharmacyclics LLC.: lead
• Janssen Research & Development, LLC: collaborator

Study Sites (46)

City of Hope /ID# 1142-0047

Duarte, California, 91010, United States

Location

Moores Cancer Center at UC San Diego /ID# 1142-0241

La Jolla, California, 92093, United States

Location

UC Irvine Medical Center - Chao Family Comprehensive Cancer Center /ID# 1142-0008

Orange, California, 92868-3201, United States

Location

Norton Cancer Center /ID# 1142-0071

Louisville, Kentucky, 40202, United States

Location

Rutgers Cancer Institute of New Jersey /ID# 1142-1193

New Brunswick, New Jersey, 08901, United States

Location

Northwell Health/Long Island Jewish Hospital /ID# 1142-0350

New Hyde Park, New York, 11042, United States

Location

New York Presbyterian Hospital/Weill Cornell Med College /ID# 1142-0200

New York, New York, 10021, United States

Location

University of Rochester Cancer Center /ID# 1142-0127

Rochester, New York, 14642-0001, United States

Location

Charlotte-Mecklenberg Hospital, Carolinas Healthcare System, Levine Cancer Inst /ID# 1142-0733

Charlotte, North Carolina, 28203, United States

Location

Cleveland Clinic Foundation /ID# 1142-0739

Cleveland, Ohio, 44195, United States

Location

University of Pennsylvania /ID# 1142-0069

Philadelphia, Pennsylvania, 19104, United States

Location

Tennessee Oncology - Chattanooga /ID# 1142-0123

Chattanooga, Tennessee, 37404-1108, United States

Location

MD Anderson Cancer Center /ID# 1142-0032

Houston, Texas, 77030, United States

Location

Swedish Cancer Institute /ID# 1142-0114

Seattle, Washington, 98104, United States

Location

St George Hospital /ID# 1142-0654

Kogarah, New South Wales, 2217, Australia

Location

Flinders Medical Centre /ID# 1142-0163

Bedford Park, South Australia, 5042, Australia

Location

Monash Medical Centre /ID# 1142-0556

Clayton, Victoria, 3168, Australia

Location

Peter MacCallum Cancer Centre-East Melbourne /ID# 1142-0633

East Melbourne, Victoria, 3002, Australia

Location

St Vincent's Hospital Melbourne /ID# 1142-0501

Fitzroy, Victoria, 3065, Australia

Location

Frankston Hospital /ID# 1142-0715

Frankston, Victoria, 3199, Australia

Location

Austin Health /ID# 1142-0170

Heidelberg, Victoria, 3084, Australia

Location

Ospedale San Raffaele IRCCS /ID# 1142-0523

Milan, Lombardy, 20132, Italy

Location

Ospedale Policlinico San Martino /ID# 1142-0903

Genova, 16132, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda /ID# 1142-0581

Milan, 20162, Italy

Location

Azienda Ospedaliero-Universitaria di Modena /ID# 1142-0524

Modena, 41124, Italy

Location

Azienda Ospedaliero Universitaria Maggiore della Carita di Novara /ID# 1142-0582

Novara, 28100, Italy

Location

Azienda Ospedaliera di Padova /ID# 1142-1175

Padua, 35128, Italy

Location

Azienda USL di Piacenza - Ospedale Guglielmo da Saliceto /ID# 1142-1182

Piacenza, 29121, Italy

Location

Middlemore Hospital /ID# 1142-0662

Otahuhu, Auckland, 2025, New Zealand

Location

Christchurch Hospital /ID# 1142-0589

Christchurch, Canterbury, 8011, New Zealand

Location

Palmerston North Hospital /ID# 1142-0585

Palmerston North, Manawatu-Wanganui, 4414, New Zealand

Location

North Shore Hospital /ID# 1142-0663

Auckland, 0622, New Zealand

Location

Malopolskie Centrum Medyczne /ID# 1142-0364

Krakow, Lesser Poland Voivodeship, 30-510, Poland

Location

Duplicate_Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie /ID# 1142-0590

Lublin, Lublin Voivodeship, 20-081, Poland

Location

Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. ks. B. /ID# 1142-0592

Brzozów, Podkarpackie Voivodeship, 36-200, Poland

Location

Samodzielny Publiczny Szpital Klinczny Nr-1- Akademickie Cenrum Klinic /ID# 1142-0529

Gdansk, Pomeranian Voivodeship, 80-952, Poland

Location

Medical Univ. of Lodz and Copernicus Memorial Hospital /ID# 1142-0531

Lodz, 93-510, Poland

Location

Hospital Duran i Reynals /ID# 1142-0604

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital Universitario Puerta de Hierro, Majadahonda /ID# 1142-0536

Majadahonda, Madrid, 28222, Spain

Location

Complejo Hospitalario de Navarra /ID# 1142-1197

Pamplona, Navarre, 31008, Spain

Location

Hospital Clinic de Barcelona /ID# 1142-0533

Barcelona, 08036, Spain

Location

Hospital Santa Creu i Sant Pau /ID# 1142-0535

Barcelona, 08041, Spain

Location

Hospital Universitario Virgen de las Nieves /ID# 1142-1196

Granada, 18014, Spain

Location

Hospital Universitario Ramon y Cajal /ID# 1142-0874

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre /ID# 1142-0864

Madrid, 28041, Spain

Location

Hospital Clinico Universitario de Salamanca /ID# 1142-0790

Salamanca, 37007, Spain

Location

Related Publications (2)

• 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.

  PMID: 37315225 DERIVED

• 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.

  PMID: 34618601 DERIVED

MeSH Terms

Conditions

Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

ibrutinib; venetoclax

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

abbvieclinicaltrials@abbvie.com

800-633-9110

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants with confirmed undetectable minimal residual disease (uMRD) in the MRD cohort are triple masked. Allocation was not randomized for the Fixed Duration (FD) cohort.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2016
• First Posted: September 22, 2016
• Study Start: September 28, 2016
• Primary Completion: November 12, 2020
• Study Completion: March 27, 2024
• Last Updated: December 20, 2024
• Results First Posted: February 18, 2022

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR

Locations

PL (5); ES (9); IT (7); NZ (4); US (14); AU (7)