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Diffuse Large B-cell LymphomaPhase 2NCT03123393

TAK-659 in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

A Phase 2 study testing TAK-659 in people with Diffuse Large B-cell Lymphoma, run by Calithera Biosciences, Inc at 41 sites in 6 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study is to assess the efficacy of TAK-659 measured by independent radiologic review committee (IRC)-assessed overall response rate (ORR) in participants with relapsed or refractory DLBCL. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Diffuse Large B-cell Lymphoma
What is being tested?
TAK-659
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
49 participants
Where
41 sitesin 6 countries
Study dates
10 Oct 2017to 17 Dec 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Must have histologically confirmed DLBCL, including de novo disease or transformed disease from indolent NHL.
  • High-grade B-cell lymphoma (BCL) with MYC and BCL-2 and/or BCL-6 translocations (double-hit DLBCL under DLBCL, not otherwise specified [NOS], based on the 2008 World Health Organization [WHO] classification criteria) is not eligible for this study.
  • Local pathology review for histological confirmation; A formalin-fixed, paraffin-embedded (FFPE) tumor block or appropriately stained slides from a fresh biopsy is required.
  • Relapsed or refractory to greater than or equal to (>=) 2 prior lines of chemotherapy based on standard of care with certain requirements for prior therapy.
  • Documented investigator-assessed relapse or progression after the last treatment is required if the participant responded and then progressed on the prior treatment.
  • Measurable disease per IWG 2007 criteria.
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  • Eastern Cooperative Oncology Group (ECOG) performance status less than (<) 2.
  • Life expectancy of greater than (>) 3 months.
  • Adequate organ function, including the following:
  • Bone marrow reserve: absolute neutrophil count (ANC) >=1000/microliter (μL), platelet count >=75,000/μL (>=50,000/μL for participants with bone marrow involvement), and hemoglobin >=8 gram per deciliter (g/dL).
  • Hepatic: total bilirubin less than or equal to (<=) 1.5 times the upper limit of the normal range (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=2.5*ULN.
  • Renal: creatinine clearance >=60 milliliter per minute (mL/min).
  • Others:
  • Lipase <=1.5*ULN and amylase <=1.5*ULN with no clinical symptoms suggestive of pancreatitis or cholecystitis.
  • Blood pressure <=Grade 1 (hypertensive participants are permitted if their blood pressure is controlled to <=Grade 1 by hypertensive medications.
  • Glycosylated hemoglobin is <=6.5% hyperglycemic participants permitted if glucose is well controlled by antihyperglycemic medication).

Who cannot join

  • Central nervous system (CNS) lymphoma; active brain or leptomeningeal metastases.
  • Known human immunodeficiency virus (HIV)-related malignancy.
  • Systemic anticancer treatment (including investigational agents) less than 3 weeks before the first dose of study treatment (<=4 weeks for antibody-based therapy including unconjugated antibody, antibody-drug conjugate, and bi-specific T-cell engager agents; <=8 weeks for cell-based therapy or anti-tumor vaccine).
  • Radiotherapy less than 3 weeks before the first dose of study treatment. If prior radiotherapy occurred <4 to 6 weeks before study start, as radiated lesions cannot be reliably assessed by fluorodeoxyglucose-positron emission tomography (FDG-PET), nonradiated target lesions are required for eligibility, and prior radiotherapy information must be submitted to the IRC.
  • Known HIV positive, hepatitis B surface antigen positive or known or suspected active hepatitis C infection.
  • Prior autologous stem cell transplant (ASCT) within 6 months or prior ASCT at any time without full hematopoietic recovery before Cycle 1 Day 1, or allogeneic stem cell transplant any time.
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  • Participants with certain cardiovascular conditions are excluded.
  • Major surgery within 14 days before the first dose of study drug or incomplete recovery from any complications from surgery.
  • Systemic infection requiring parenteral antibiotic therapy or other serious infection (bacterial, fungal, or viral) within 21 days before the first dose of study drug.
  • Treatment with high-dose corticosteroids for anticancer purposes within 7 days before the first dose of TAK-659.
  • Participants with another malignancy within 2 years of study start. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection and are considered disease-free at the time of study entry.
  • Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of TAK-659.
  • Received medications, supplements, or food/beverages that are P-glycoprotein (P-gp) inhibitors or inducers or strong cytochrome P450 (CYP) 3A inhibitors or inducers within a certain timeframe prior to the first dose of study drug. Depending on the substance, the washout period for P-gp inhibitors or inducers or strong CYP3A inhibitors or inducers will be either 7 days or 5 times the half-life (half-life is related to the time required for elimination from the body). The washout period for grapefruit containing food or beverages is 5 days.

Trial locations and contacts

41 sites in 6 countries.

41 sites in 6 countries

United States10 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109-1274

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Swedish Medical Oncology - Edmonds

    Edmonds, Washington, 98026

  • Swedish Cancer Institute - Issaquah

    Issaquah, Washington, 98029

  • New York University Langone Medical Center

    New York, New York, 10016

  • Perelman Center for Advanced Medicine

    Philadelphia, Pennsylvania, 19104

  • Swedish Health Services

    Seattle, Washington, 98104

  • University of Washington, Hutchinson Cancer Research Center

    Seattle, Washington, 98109

  • Swedish First Hill Campus

    Seattle, Washington, 98122

  • University of Kansas Medical Center

    Westwood, Kansas, 66205

Other trials in United States

France10 sites

  • CHRU Clermont- Ferrand CHU Estaing

    Clermont-Ferrand, Auvergne, 63000

  • Hopital Dupuytren

    Limoges, Limousin, Lorraine, 87042

  • Institut Paoli Calmettes Departement de Recherche Clinique et de l'Innovation

    Marseille, Provence-Alpes-Côte d'Azur Region, 13009

  • Hopital Necker-Enfants Malades

    Paris, Île-de-France Region, 75015

  • Hopital Saint Louis

    Paris, Île-de-France Region, 75475

  • Groupe Hospitalier - Hopitaux Universitaires Pitie-Salpetriere - Charles-Foix - Pitie-Salpetriere

    Paris, Île-de-France Region, 75651

  • Hopital Haut-Leveque

    Pessac, Aquitaine, 33604

  • Centre Hospitalier Lyon Sud

    Pierre-Bénite, Auvergne-Rhône-Alpes, 69495

  • Centre Henri-Becquerel

    Rouen, Haute-normandie, 76038

  • Institut Gustave Roussy

    Villejuif, Île-de-France Region, 94805

Other trials in France

Spain7 sites

  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

  • Hospital Clinic de Barcelona

    Barcelona, 08036

  • Hospital General Universitario Gregorio Maranon

    Madrid, 28009

  • Hospital Universitario La Paz

    Madrid, 28046

  • Hospital Universitario de Salamanca

    Salamanca, 37007

  • Hospital Universitario Marques de Valdecilla

    Santander, 39008

  • Hospital Universitario La Fe

    Valencia, 46026

Other trials in Spain

Italy6 sites

  • Azienda Ospedaliera Papa Giovanni XXIII

    Bergamo, 24127

  • Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

    Milan, 20162

  • Azienda Ospedaliero-Universitaria "Maggiore della Carita"

    Novara, 28100

  • Ospedale Casa Sollievo della Sofferenza

    San Giovanni Rotondo, Foggia, 71013

  • Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino

    Turin, Piedmont, 10126

  • Azienda Ospedaliero Universitaria Santa Maria della Misericordia di Udine

    Udine, 33100

Other trials in Italy

United Kingdom5 sites

  • University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital

    Birmingham, England, B15 2GW

  • London North West Healthcare NHS Trust, Imperial College London

    Harrow, England, HA1 3UJ

  • University College London Hospitals NHS Foundation Trust

    London, England, NW1 2BU

  • The Christie NHS Foundation Trust

    Manchester, England, M20 4BX

  • Newcastle Hospitals NHS Foundation Trust

    Newcastle upon Tyne, England, NE7 7DN

Other trials in United Kingdom

Canada3 sites

  • CHU de Quebec -Universite Laval-Hopital de L'Enfant Jesus

    Québec, Quebec, G1J 1Z4

  • Centre Hospitalier Regional de Rimouski

    Rimouski, Quebec, G5L 5T1

  • Princess Margaret Cancer Center

    Toronto, Ontario, M5G2M9

Other trials in Canada

About this study

Official title: Phase 2 Study of TAK-659 in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma After at Least 2 Prior Lines of Chemotherapy

The purpose of this study is to assess the efficacy of TAK-659 measured by independent radiologic review committee (IRC)-assessed overall response rate (ORR) in participants with relapsed or refractory DLBCL.

Read the detailed description

The drug being tested is TAK-659. This study will evaluate overall response rate (ORR) in participants with relapsed or refractory DLBCL who take TAK-659.

The study will enroll approximately 122 participants. Participants will be assigned to:

  • TAK-659 60 mg to 100 mg

All participants will be asked to take the tablets of TAK-659 at the same time each day throughout the study in a 28-day cycle.

This multi-center trial will be conducted in the United States, United Kingdom, Spain, Italy, France, Canada, Germany. The overall time to participate in this study is approximately 48 months. Participants will be assessed for disease response and progression during the PFS follow-up every 3 months after end of treatment (for participants who discontinue due to reasons other than disease progression) and OS follow-up every 3 months from the last dose of study drug until death or conclusion of the study, whichever occurs first.

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

What participants receive

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

  • TAK-659Drug

    TAK-659 Tablets

Study groups in NCT03123393
Study groupRoleWhat they receive
Cohort A: TAK-659 100 mgExperimentalTAK-659 100 mg tablet, orally, once daily (QD), during each 28-days cycle (median exposure was 41 days).
Receives: Drug: TAK-659
Cohort B: TAK-659 Ramp-up DosingExperimentalTAK-659 60-100 mg tablet, orally, QD, dose based on safety and tolerability during each 28-days cycle (median exposure was 28 days).
Receives: Drug: TAK-659

What is being measured

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

  1. Stage 2: ORR as Assessed by Independent Radiologic Review Committee (IRRC) Based on Modified 2007 International Working Group (IWG) Criteria

    ORR was defined as the percentage of participants with complete response (CR), or partial response (PR) as assessed by IRRC according to the modified 2007 IWG criteria for malignant lymphoma. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.

    Measured: Up to 12 months

Secondary outcomes (11)

  1. Stage 2: CR Rate as Assessed by IRC Based on Modified 2007 IWG Criteria

    CR rate was defined as percentage of participants with complete response as assessed by IRC according to the modified 2007 IWG. CR was defined as disappearance of all evidence of disease.

    Measured: Up to 12 months

  2. Stage 2: ORR as Assessed by IRRC Based on 2014 IWG-Lugano Criteria

    ORR was defined as the percentage of participants with CR or PR as assessed by IRRC according to the 2014 Lugano classification, IWG criteria for malignant lymphoma. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.

    Measured: Up to 12 months

  3. Stage 2: CR Rate as Assessed by IRRC Based on 2014 IWG-Lugano Criteria

    CR rate was defined as percentage of participants with complete response as assessed by IRC according to the 2014 Lugano classification, IWG criteria. CR was defined as disappearance of all evidence of disease.

    Measured: Up to 12 months

  4. Stage 2: Duration of Response (DOR)

    DOR was defined as the time from the date of first documentation of a CR/PR to the date of first documentation of tumor progression or progressive disease (PD) per IRRC assessment according to IWG criteria. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites. PD was defined as presence of any new lesion or increase by >=50% of previously involved sites from nadir.

    Measured: Up to 12 months

  5. Stage 2: Duration of CR

    Duration of CR was defined as the time from the date of first documentation of a CR/PR to the date of first documentation of tumor progression or PD per IRRC assessment according to IWG criteria. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites. PD was defined as presence of any new lesion or increase by >=50% of previously involved sites from nadir.

    Measured: Up to 12 months

  6. Stage 2: ORR as Assessed by IRRC in Participants With Germinal Center B-cell (GCB) DLBCL

    ORR was defined as the percentage of participants with CR or PR as assessed by IRRC according to the modified 2007 IWG criteria for malignant lymphoma. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.

    Measured: Up to 12 months

  7. Stage 2: ORR as Assessed by IRC in Participants With DLBCL Transformed From Indolent Non-Hodgkin's Lymphoma (NHL)

    ORR was defined as the percentage of participants with CR or PR as assessed by IRC according to the modified 2007 IWG criteria for malignant lymphoma. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.

    Measured: Up to 12 months

  8. Stage 2: Progression Free Survival (PFS) as Assessed by IRC

    PFS was defined as time from start of study treatment to first documentation of PD per IRC assessment or up to death due to any cause, whichever occurs first based on IWG criteria. PD was defined as presence of any new lesion or increase by >=50% of previously involved sites from nadir.

    Measured: Up to 18 months

  9. Stage 2: Overall Survival (OS)

    OS was defined as the time from start of study treatment to date of death due to any cause.

    Measured: Up to 24 months

  10. Stage 1: ORR as Assessed by IRRC to Select Stage 2 Dose Regimen of TAK-659 From the Lead-in Dose Exploration Phase

    ORR was defined as the percentage of participants with CR or PR as assessed by IRC. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.

    Measured: Up to 12 months

  11. Stage 2: ORR as Assessed by IRC at 3, 6, and 9 Cycles in Participants With DLBCL

    ORR was defined as the percentage of participants with CR or PR as assessed by IRC according to the modified 2007 IWG criteria for malignant lymphoma. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.

    Measured: At Cycles 3, 6 and 9 (Up to 12 months) (Each cycle of 28 days)

Timeline

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

  1. First posted21 Apr 2017
  2. Study start10 Oct 2017
  3. Primary completion17 Dec 2019
  4. Study completion17 Dec 2019

Why it stopped: Lack of efficacy of the drug; no safety concern

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
49 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03123393
Sponsor's protocol ID
C34004
Other IDs
U1111-1187-6208, 2016-003716-12, 17/YH/0181, 2016
Status last verified
Feb 2023
First submitted
17 Apr 2017
Last updated
8 Feb 2023
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing TAK-659 in people with Diffuse Large B-cell Lymphoma, run by Calithera Biosciences, Inc at 41 sites in 6 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 16 inclusion and 13 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: stopped early, 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 41 sites in United States, France, Spain, Italy, United Kingdom and 1 more country. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Stage 2: ORR as Assessed by Independent Radiologic Review Committee (IRRC) Based on Modified 2007 International Working Group (IWG) Criteria (time frame: Up to 12 months). 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 NCT03123393.

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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