A Study of TAK-659 in Combination With Venetoclax for Adult Participants With Previously Treated Non-Hodgkin Lymphoma
A Phase 1b Study of TAK-659 in Combination With Venetoclax for Adult Patients With Previously Treated Non-Hodgkin Lymphoma
3 other identifiers
interventional
43
3 countries
15
Brief Summary
The purpose of this study is to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of TAK-659 and venetoclax when administered in combination in participants with non-Hodgkin lymphoma (NHL) relapsed and/or refractory after at least 1 prior line of therapy and to evaluate safety and tolerability of TAK-659 and venetoclax when administered in combination.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Feb 2018
Typical duration for phase_1
15 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 25, 2017
CompletedFirst Posted
Study publicly available on registry
November 30, 2017
CompletedStudy Start
First participant enrolled
February 16, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 3, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
August 3, 2021
CompletedFebruary 8, 2023
February 1, 2023
3.5 years
November 25, 2017
February 6, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Number of Participants with a Dose Limiting Toxicity (DLT)
Toxicity will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE), Version 5.0 DLT will be defined as any of the events specified in the protocol that are considered by the investigator to be at least possibly related to therapy with study medications and that occur within the first cycle.
Baseline up to 5 weeks
Percentage of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs), Grade 3 or Higher Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Discontinuation
AE Grades will be evaluated as per NCI CTCAE, version 5.0.
Baseline up to 13 months
Secondary Outcomes (13)
Cmax: Maximum Observed Plasma Concentration for TAK-659 and Venetoclax
Cycle 1 Days 1 and 21 or 28: Pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length is equal to [=] 35 days)
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659 and Venetoclax
Cycle 1 Days 1 and 21 or 28: Pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length =35 days)
AUCÏ„: Area Under the Plasma Concentration-time Curve from Time 0 to Time Over the Dosing Interval for TAK-659 and Venetoclax
Cycle 1 Days 1 and 21 or 28: Pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length =35 days)
Oral Clearance (CL/F) for TAK-659 and Venetoclax
Cycle 1 Days 1 and 21 or 28: Pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length =35 days)
Peak-trough Ratio (PTR) for TAK-659 and Venetoclax
Cycle 1 Days 1 and 21 or 28: Pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length =35 days)
- +8 more secondary outcomes
Study Arms (3)
Dose Escalation: TAK-659 + Venetoclax
EXPERIMENTALTAK-659 40, 60, 80, or 100 milligram (mg) (tablet, orally, once daily, up to 35 days in Cycle 1 or in different intermittent schedules \[7 days dosing followed by 7 days off or 14 days dosing followed by 7 days off or other intermittent dosing schedules\]) along with venetoclax 200, 400, 800 or 1200 mg (tablet, orally, once daily, up to 35 days in Cycle 1). After Cycle 1, TAK-659 and venetoclax will be administered once daily in a 28-day treatment cycle until disease progression, unacceptable toxicities, or discontinuation by participant.
Safety Expansion: Diffuse Large B-cell Lymphoma (DLBCL) Cohort
EXPERIMENTALTAK-659 tablet, orally, once daily along with venetoclax tablet, orally, once daily in a 28-day treatment cycle until disease progression, unacceptable toxicities, or discontinuation by participant. TAK-659 and venetoclax MTD/RP2D will be determined from the dose escalation phase.
Safety Expansion: Follicular Lymphoma (FL) Cohort
EXPERIMENTALTAK-659 tablet, orally, once daily along with venetoclax tablet, orally, once daily in a 28-day treatment cycle until disease progression, unacceptable toxicities, or discontinuation by participant. TAK-659 and venetoclax MTD/RP2D will be determined from the dose escalation phase.
Interventions
TAK-659 tablets.
Venetoclax tablets.
Eligibility Criteria
You may qualify if:
- For the Dose Escalation phase, participants must have histologically confirmed diagnosis of advanced NHL of any histology (with the exception of participants with mantle cell lymphoma \[MCL\] or chronic lymphoma leukemia \[CLL\]).
- For the Safety Expansion phase, participants must have histologically confirmed diagnosis of advanced DLBCL or FL.
- Radiographically or clinically measurable disease with greater than or equal to (\>=) 1 target lesion per IWG criteria for malignant lymphoma.
- Refractory or relapsed after at least 1 prior line of therapy for whom no effective standard therapy is available per investigator's assessment.
- o Participants who are either treatment-naive to, relapsed after, or refractory to ibrutinib, idelalisib, or any other investigational B cell receptor (BCR) pathway inhibitors not directly targeting spleen tyrosine kinase (SYK) are allowed.
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
- Life expectancy of greater than 3 months.
- Suitable venous access for the study-required blood sampling that is, including PK and pharmacodynamic sampling.
- Recovered (that is, less than or equal to \[\<=\] Grade 1 toxicity) from the reversible effects of prior anticancer therapy.
You may not qualify if:
- Central nervous system (CNS) lymphoma; active brain or leptomeningeal metastases, as indicated by positive cytology from lumbar puncture or computed tomography (CT) scan/magnetic resonance imaging (MRI).
- History of drug-induced pneumonitis requiring treatment with steroids; history of idiopathic pulmonary fibrosis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted.
- Participants requires the use of warfarin (use in prophylactic doses \[example, deep vein thrombosis prophylaxis\]) is allowed.
- Prior exposure to targeted SYK inhibitors.
- History of a prior intolerable toxicity, in the opinion of the investigator from another B-cell lymphoma (BCL)-2 family protein inhibitor study.
- Participants who are relapsed after or refractory to regimens containing venetoclax or other BCL2 inhibitors.
- Systemic anticancer treatment (including investigational agents) or radiotherapy less than 2 weeks before the first dose of study treatment (\<=4 weeks for large molecule agents; \<=8 weeks for cell-based therapy or anti-tumor vaccine), or not recovered from the reversible effects of prior anticancer therapy.
- Prior autologous stem cell transplant (ASCT) within 6 months preceding Cycle 1 Day 1.
- Prior allogeneic stem cell transplant and/or chimeric antigen receptor T-cell therapy at any time.
- Major surgery within 14 days before the first dose of study drug and not recovered fully from any complications from surgery.
- Known human immunodeficiency virus (HIV) positive or HIV-related malignancy.
- Received a live viral vaccine within 6 months prior to the first dose of study drug.
- Use or consumption of:
- Medications or supplements that are known to be strong or moderate Cytochrome P4503A (CYP3A) inhibitors or strong or moderate CYP3A inducers and/or P-glycoprotein (P-gp) inhibitors or inducers within 7 days or within 5 times the inhibitor or inducer half-life (whichever is longer) before the first dose of study drugs. In general, the use of these agents is not permitted during the study except in cases in which an adverse event (AE) must be managed during interruption of study drug dosing.
- Food or beverages containing grapefruit, Seville oranges, or Star fruit within 5 days before the first dose of study drugs. Note that food and beverages containing grapefruit, Seville orange, or Star fruit are not permitted during the study.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (15)
University of Alabama at Birmingham
Birmingham, Alabama, 35249, United States
Emory University
Atlanta, Georgia, 30322, United States
NorthShore Medical Group - Evanston
Evanston, Illinois, 60201, United States
Ingalls Memorial Hospital
Harvey, Illinois, 60426, United States
Norton Cancer Institute - Shelbyville
Shelbyville, Kentucky, 40065, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Icahn School of Medicine at Mount Sinai
New York, New York, 10029, United States
Baylor Scott & White Research Institute
Dallas, Texas, 75246, United States
Hopital Maisonneuve-Rosemont
Montreal, Quebec, H1T 2M4, Canada
Jewish General Hospital
Montreal, Quebec, H3T 1E2, Canada
Universitatsklinikum Heidelberg
Heidelberg, Baden-Wurttemberg, 69120, Germany
Universitatsklinikum Ulm
Ulm, Baden-Wurttemberg, 89081, Germany
Universitatklinikum der Ludwig-Maximilians-Universitat Munchen
München, Bavaria, 81377, Germany
Universitatsklinikum Frankfurt
Frankfurt am Main, Hesse, 60590, Germany
Universitatsmedizin der Johannes Gutenberg Universitat
Mainz, Rhineland-Palatinate, 55131, Germany
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Medical Director
Millennium Pharmaceuticals, Inc.
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- OTHER
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 25, 2017
First Posted
November 30, 2017
Study Start
February 16, 2018
Primary Completion
August 3, 2021
Study Completion
August 3, 2021
Last Updated
February 8, 2023
Record last verified: 2023-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Access Criteria
- IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.