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Lymphoma, Non-HodgkinPhase 1NCT03357627

A Study of TAK-659 in Combination With Venetoclax for Adult Participants With Previously Treated Non-Hodgkin Lymphoma

A Phase 1 study testing TAK-659 and Venetoclax in people with Lymphoma, Non-Hodgkin and Lymphoma, Large B-cell, Diffuse, run by Calithera Biosciences, Inc at 15 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
TAK-659 and Venetoclax
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
15 sitesin 3 countries
Study dates
16 Feb 2018to 3 Aug 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.
  • Preparations containing St. John's wort within 7 days before the first dose of study drugs. Note that preparations containing St. John's wort are not permitted during the study.

Trial locations and contacts

15 sites in 3 countries.

15 sites in 3 countries

United States8 sites

  • Emory University

    Atlanta, Georgia, 30322

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35249

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Baylor Scott & White Research Institute

    Dallas, Texas, 75246

  • NorthShore Medical Group - Evanston

    Evanston, Illinois, 60201

  • Ingalls Memorial Hospital

    Harvey, Illinois, 60426

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

  • Norton Cancer Institute - Shelbyville

    Shelbyville, Kentucky, 40065

Other trials in United States

Germany5 sites

  • Universitatsklinikum Frankfurt

    Frankfurt am Main, Hesse, 60590

  • Universitatsklinikum Heidelberg

    Heidelberg, Baden-Wurttemberg, 69120

  • Universitatsmedizin der Johannes Gutenberg Universitat

    Mainz, Rhineland-Palatinate, 55131

  • Universitatklinikum der Ludwig-Maximilians-Universitat Munchen

    München, Bavaria, 81377

  • Universitatsklinikum Ulm

    Ulm, Baden-Wurttemberg, 89081

Other trials in Germany

Canada2 sites

  • Hopital Maisonneuve-Rosemont

    Montreal, Quebec, H1T 2M4

  • Jewish General Hospital

    Montreal, Quebec, H3T 1E2

Other trials in Canada

About this study

Official title: A Phase 1b Study of TAK-659 in Combination With Venetoclax for Adult Patients With Previously Treated Non-Hodgkin Lymphoma

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.

Read the detailed description

The drugs being tested in this study are called TAK-659 and venetoclax. TAK-659 in combination with venetoclax is being tested to treat people who have advanced NHL after at least 1 prior line of therapy. This study will look at the safety data, pharmacokinetic (PK) data and any early anti-tumor activity observed.

The study will enroll approximately 53 participants.

  • TAK-659 and venetoclax doses will be escalated according to a Bayesian logistic regression model (BLRM) with overdose control escalation schema. TAK-659 60 mg + Venetoclax 400 mg is the starting dose.

Participants could also receive 40 mg, 60 mg, 80 mg or 100 mg TAK-659 during dose escalation and 200 mg, 400 mg, 800 mg, or 1200 mg of venetoclax.

Following dose escalation the safety and tolerability of the MTD/RP2D of the TAK-659+venetoclax combination will be further explored in two dose-safety expansion cohorts, Cohort A in participants with DLBCL and Cohort B in participants with FL.

All participants will be asked to take one tablet of TAK-659 on an empty stomach at least 1 hour before and no sooner than 2 hours after eating food and/or drinking fluids other than water. Venetoclax will be taken with a meal and water 2 hours after TAK-659 has been taken. No food or drink (except water) are allowed between TAK-659 and venetoclax. TAK-659 and venetoclax should be taken at the same time each day throughout the study.

This multi-center trial will be conducted in the United States, Canada and Europe. The overall time to participate in this study is 20 months or until disease progression, unacceptable toxicities, or withdrawal from study by participant. Participants will make multiple visits to the clinic, and will be followed for 28 days (+10) days after the last dose of TAK-659 or venetoclax or the start of subsequent alternative anticancer therapy to permit the detection of any delayed treatment-related AEs. For participants enrolled in either the dose escalation or safety expansion phases, the maximum duration of treatment will be 12 months unless, in the opinion of the investigator and with the agreement of the sponsor, the participant would derive benefit from continued therapy beyond 12 months. Participants enrolled in the safety expansion part who stop treatment for any reason other than disease progression will continue PFS follow-up every 2 months after the last dose of study drug for up to 6 months or until disease progression or the start of alternative therapy, whichever occurs first.

Being tested
TAK-659, Venetoclax
Keywords
Drug therapy
Medical subject headings
Lymphoma, Non-Hodgkin, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TAK-659Drug

    TAK-659 tablets.

  • VenetoclaxDrug

    Venetoclax tablets.

Study groups in NCT03357627
Study groupRoleWhat they receive
Dose Escalation: TAK-659 + VenetoclaxExperimentalTAK-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.
Receives: Drug: TAK-659; Drug: Venetoclax
Safety Expansion: Diffuse Large B-cell Lymphoma (DLBCL) CohortExperimentalTAK-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.
Receives: Drug: TAK-659; Drug: Venetoclax
Safety Expansion: Follicular Lymphoma (FL) CohortExperimentalTAK-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.
Receives: Drug: TAK-659; Drug: Venetoclax

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline up to 5 weeks

  2. 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.

    Measured: Baseline up to 13 months

Secondary outcomes (13)

  1. Cmax: Maximum Observed Plasma Concentration for TAK-659 and Venetoclax

    Measured: 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)

  2. Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659 and Venetoclax

    Measured: 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)

  3. AUCτ: Area Under the Plasma Concentration-time Curve from Time 0 to Time Over the Dosing Interval for TAK-659 and Venetoclax

    Measured: 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)

  4. Oral Clearance (CL/F) for TAK-659 and Venetoclax

    Measured: 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)

  5. Peak-trough Ratio (PTR) for TAK-659 and Venetoclax

    Measured: 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)

  6. Accumulation Ratio (Rac) for TAK-659 and Venetoclax

    Measured: 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)

  7. Trough Concentration (C trough) for TAK-659 and Venetoclax

    Measured: 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. Overall Response Rate (ORR)

    ORR is calculated as percentage of participants with complete response (CR) + percentage of participants with partial response (PR) as assessed by International Working Group (IWG) criteria for malignant lymphoma.

    Measured: Up to 12 months

  9. Duration of Overall Response

    Measured: Up to 12 months

  10. CR Rate

    CR rate is calculated as percentage of participants with CR as assessed by IWG criteria for malignant lymphoma.

    Measured: Up to 12 months

  11. Duration of CR

    Measured: Up to 12 months

  12. Time to Progression (TTP)

    TTP will be measured as the time in months from the first dose of study treatment to the date of the first documented disease progression as assessed using IWG criteria.

    Measured: Up to 13 months

  13. Progression-free Survival (PFS)

    PFS is defined as the time from date of first study drug administration to the day of first documented disease progression or death due to any cause, whichever occurs first.

    Measured: Up to 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Nov 2017
  2. Study start16 Feb 2018
  3. Primary completion3 Aug 2021
  4. Study completion3 Aug 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Other
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03357627
Sponsor's protocol ID
C34008
Other IDs
2017-002872-14, U1111-1203-9951, 2017
Status last verified
Feb 2023
First submitted
25 Nov 2017
Last updated
8 Feb 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TAK-659 and Venetoclax in people with Lymphoma, Non-Hodgkin and Lymphoma, Large B-cell, Diffuse, run by Calithera Biosciences, Inc at 15 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States, Germany, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants with a Dose Limiting Toxicity (DLT) (time frame: Baseline up to 5 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03357627.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2023.

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