AzTrials
AzTrials

Lymphoma, Non-HodgkinPhase 1/2NCT04074330

A Study of TAK-981 Given With Rituximab in Adults With Relapsed or Refractory CD20-Positive Non-Hodgkin Lymphoma

A Phase 1/2 study testing TAK-981 and Rituximab in people with Lymphoma, Non-Hodgkin, run by Takeda at 59 sites in 9 countries.

Terminated

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

Official record
Search all trials

Trial summary

This study is about a medicine called TAK-981 given with rituximab, used to treat adults with relapsed or refractory CD20-positive non-Hodgkin lymphoma. This study has 2 parts. The main aims of the study are: To check for side effects from treatment with TAK-981 given with rituximab. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma, Non-Hodgkin
What is being tested?
TAK-981 and Rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
59 sitesin 9 countries
Study dates
15 Oct 2019to 26 Apr 2023
Phase
Phase 1/2
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

  • Each participant must meet all the following inclusion criteria to be enrolled in the study:
  • Participant Population:
  • For Phase 1 Dose Escalation: o. aNHL including mantle cell lymphoma and DLBCL histologies such as transformed DLBCL from low-grade lymphoma (follicular or others), DLBCL associated with small-cell infiltration in bone marrow, B-cell lymphoma with intermediate features between DLBCL and Burkitt's lymphoma or with intermediate features between DLBCL and Hodgkin lymphoma, FL grade 3B, and aggressive B-cell lymphoma unclassifiable who must have previously received rituximab, cyclophosphamide, doxorubicin (hydroxydaunorubicin), vincristine, (Oncovin) and prednisone (R-CHOP) (or equivalent anti-CD20 containing therapy) and 1 additional line of therapy in the r/r setting.
  • iNHL (including FL of grades 1-3A and marginal zone lymphoma) refractory to rituximab or to any other anti-CD20 monoclonal antibodies, who have received at least 1 prior systemic therapy for r/r iNHL.
  • Rituximab or anti-CD20 refractoriness is defined as failure to respond to, or progression during, any previous rituximab/anti-CD20-containing regimen (monotherapy or combined with chemotherapy), or progression within 6 months of the last rituximab or anti-CD20 dose.
  • Note: The minimum qualifying rituximab/anti-CD20 dose is 1 full cycle (that is, weekly4 doses monotherapy or 1 complete dose if combined with chemotherapy). Prior anti-CD20 antibody or cytotoxic drugs may have been administered as single agents or as components of combination therapies. Each repeated course of the same single-agent or combination is considered an independent regimen.
Show all 23Show fewer
  • For Phase 2, the following confirmed CD20+: o. r/r DLBCL progressed or relapsed after a prior CAR T-cells therapy that has received approval by a health authority for the treatment of DLBCL (Cohort A).
  • r/r DLBCL that has progressed or relapsed after at least 2 but no more than 3 prior lines of systemic therapy and has not I prior cellular therapy. At least one prior line of therapy must have included a CD20-targeted therapy (Cohort B).
  • r/r FL that has progressed or relapsed after at least 2 but no more than 3 prior lines of systemic therapy. At least 1 prior line of therapy must have included a CD20-targeted therapy (Cohort C).
  • Must be considered ineligible in the opinion of the investigator, or refused autologous stem-cell transplantation (ASCT).
  • Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to (<=) 2.
  • Adequate bone marrow function per local laboratory reference range at screening as follows:
  • o Platelet count greater than or equal to (>=) 75.010^9/L, Grade 2 thrombocytopenia (platelet count >=50.010^9 per liter [/L]) is allowed if it is clearly due to marrow involvement with no evidence of myelodysplastic syndrome or hypoplastic bone marrow if found. Absolute neutrophil count (ANC) >=1.010^9/L. Hemoglobin >=85 gram per liter (g/L) (red blood cell [RBC] transfusion allowed >=14 days before assessment).
  • Adequate renal and hepatic function, per local laboratory reference range at screening as follows:
  • Calculated creatinine clearance >=30 milliliter per minute (mL/min) calculated with Cockcroft-Gault formula.
  • Potassium levels >=lower limit of normal (LLN). For potassium >upper limit of normal (ULN) discussion with Takeda medical monitor (MM)/designee recommended.
  • Aspartate aminotransferase and alanine aminotransferase <=3.0*the ULN of the institution's normal range; bilirubin <=1.5*ULN. Participants with Gilbert's syndrome may have a bilirubin level >1.5*ULN, per discussion between the investigator and the medical monitor.
  • Left ventricular ejection fraction (LVEF) >=40 percent (%); as measured by echocardiogram or multiple gated acquisition (MUGA) scan.
  • Suitable venous access for safe drug administration and the study-required PK and pharmacodynamic sampling.
  • Have at least 1 bidimensionally measurable lesion per Lugano Classification by computed tomography (CT). Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  • Willing to consent to 1 mandatory pretreatment and 1 on-treatment skin biopsy during Phase 1. The skin biopsy entry requirement may be discontinued by the sponsor once there is enough pharmacodynamic evidence of target engagement.
  • For participants enrolled in Phase 2, if available, mandatory submission of archival tumor tissue acquired ≤12 months prior to screening.
  • Recovered to Grade 1, baseline or established as sequela, from all toxic effects of previous therapy (except alopecia, neuropathy, autoimmune endocrinopathies with stable endocrine replacement therapy, neurotoxicity [Grade 1 or 2 permitted], or bone marrow parameters [any of Grade 1, 2, permitted if directly related to bone marrow involvement]).

Who cannot join

  • Participants meeting any of the following exclusion criteria are not to be enrolled in the study:
  • Central nervous system lymphoma; active brain or leptomeningeal metastases, as indicated by positive cytology from lumbar puncture or CT scan/magnetic resonance imaging (MRI).
  • History of Grade >=3 infusion-related reaction (IRR) that lead to permanent discontinuation of previous rituximab treatment.
  • Post transplantation lymphoproliferative disease except relapsed NHL after ASCT.
  • Undergone ASCT or treatment with cellular therapy including CAR T within <=12 weeks of TAK-981 dosing.
  • Prior allogeneic hematopoietic stem-cell transplantation.
Show all 18Show fewer
  • Lymphomas with leukemic expression.
  • Prior anticancer therapy including chemotherapy, hormonal therapy, or investigational agents within 2 weeks or within at least 5 half-lives before TAK-981 dosing, whichever is shorter. Low dose steroids (oral prednisone or equivalent <=20 mg per day), hormonal therapy for prostate cancer or breast cancer (in adjuvant situation), and treatment with bisphosphonates and receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors are allowed.
  • Major surgery within 14 days before the first dose of study drug and not recovered fully from any complications from surgery.
  • Significant medical diseases or conditions, as assessed by the Investigators and sponsor that would substantially increase the risk-benefit ratio of participating in the study. This includes but is not limited to acute myocardial infarction or unstable angina within the last 6 months; uncontrolled diabetes mellitus; significant active bacterial, viral, or fungal infections; severely immunocompromised state; severe non-compensated hypertension and congestive heart failure New York Heart Association Class III or IV; ongoing symptomatic cardiac arrhythmias of >Grade 2, pulmonary embolism, or symptomatic cerebrovascular events; or any other serious cardiac condition (example, pericardial effusion or restrictive cardiomyopathy). Chronic atrial fibrillation on stable anticoagulant therapy is allowed.
  • Known chronic hepatitis C and/or positive serology (unless due to vaccination or passive immunization due to immunoglobulin [Ig] therapy) for chronic hepatitis B. Known Human Immunodeficiency Virus (HIV) infection.
  • Second malignancy within the previous 3 years, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, cervical carcinoma in situ, resected colorectal adenomatous polyps, breast cancer in situ, or other malignancy for which the participant is not on active anticancer therapy.
  • Receipt of any live vaccine within 4 weeks of initiation of study treatment.
  • Active, uncontrolled autoimmune disease requiring >20 mg of prednisone or equivalent, cytotoxics or biologicals.
  • Corticosteroid use within 1 week before the first dose of study drug, except as indicated for other medical conditions such as inhaled steroid for asthma, topical steroid use, or as premedication for administration of study drug or contrast. Participants requiring steroids at daily doses >20 mg prednisone equivalent systemic exposure daily, or those who are administered steroids for lymphoma control or white blood cell count lowering are not eligible.
  • With baseline prolongation of the QT interval with Fridericia correction method (QTcF) (example, >470 milliseconds (ms) for women and >450 ms for men and a history of congenital long QT syndrome, or torsades de pointes).
  • Receiving or requiring the continued use of medications that are known to be strong or moderate inhibitors and inducers of Cytochrome P450 3A4/5 (CYP3A4/5) and strong P-glycoprotein (Pgp) inhibitors. To participate in this study, such participants should discontinue use of such agents for at least 2 weeks (1 week for CYP3A4/5 and Pgp inhibitors) before receiving a dose of TAK-981.
  • Participants in Germany who are committed to an institution by virtue of an order issued either by judicial or administrative authorities as per German law.

Trial locations and contacts

59 sites in 9 countries.

59 sites in 9 countries

United States12 sites

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Levine Cancer Institute - Charlotte

    Chapel Hill, North Carolina, 27514

  • University of Cincinnati

    Cincinnati, Ohio, 45219

  • University Hospitals Cleveland Medical Center

    Cleveland, Ohio, 44106

  • Ohio State University Wexner Medical Center

    Columbus, Ohio, 43210

  • Texas Oncology (Medical City) - USOR

    Dallas, Texas, 75230

  • East Carolina University

    Greenville, North Carolina, 27834

  • Western Pennsylvania Hospital

    Pittsburgh, Pennsylvania, 15224

  • City of Hope - Comprehensive Cancer Center (CCC)

    Portland, Oregon, 97239

  • Mayo Clinic - Cancer Center - Rochester - PPDS

    Rochester, Minnesota, 55905

  • Texas Oncology (Tyler) - USOR

    Tyler, Texas, 75702

Other trials in United States

Italy9 sites

  • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

    Milan, Lombardy, 20122

  • Istituto Nazionale Dei Tumori

    Milan, Lombardy, 20133

  • ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda

    Milan, Lombardy, 20162

  • A.O.U. Maggiore della Carita

    Novara, Piedmont, 28100

  • Fondazione IRCCS Policlinico San Matteo di Pavia

    Pavia, 27100

  • Azienda Sanitaria Locale di Ravenna

    Ravenna, Emilia-Romagna, 48100

  • Azienda Ospedaliera San Camillo Forlanini

    Rome, Lazio, 00152

  • Azienda Ospedaliera Cardinale G Panico

    Tricase, Apulia, 73039

  • Azienda Ospedaliera Citta della Salute e della Scienza di Torino

    Turin, Piedmont, 10126

Other trials in Italy

France8 sites

  • Hopital Francois Mitterand

    Dijon, Cote-d'Or, 21000

  • Institut Paoli Calmettes

    Marseille, Bouches-du-Rhone, 13273

  • CHU Montpellier - Hopital St Eloi

    Montpellier, Herault, 34090

  • Hotel Dieu - Nantes

    Nantes, Loire-Atlantique, 44093

  • Hopital Saint Antoine

    Paris, 75012

  • Hopital Universitaire Pitie Salpetriere

    Paris, 75013

  • Hopital Prive Sevigne

    Rennes, Ille-et-Vilaine, 35000

  • Centre Henri Becquerel

    Rouen, Seine-Maritime, 76038

Other trials in France

Germany8 sites

  • Charite - Universitatsmedizin Berlin

    Berlin, 12203

  • Universitatsklinikum Essen

    Essen, North Rhine-Westphalia, 45147

  • Universitatsklinikum Freiburg

    Freiburg im Breisgau, Baden-Wurttemberg, 79106

  • Universitatsklinikum Leipzig

    Leipzig, Saxony, 04103

  • Otto-von-Guericke-Universitat Magdeburg

    Magdeburg, Saxony-Anhalt, 39120

  • Klinikum rechts der Isa der Technischen Universitaet Muenchen

    München, Bavaria, 81675

  • Universitatsklinikum Tubingen

    Tübingen, Baden-Wurttemberg, 72076

  • Universitatsklinikum Wurzburg

    Würzburg, Bavaria, 97080

Other trials in Germany

Spain7 sites

  • Hospital Clinic de Barcelona

    Barcelona, '08036

  • Hospital del Mar

    Barcelona, 08003

  • Hospital de La Santa Creu i Sant Pau

    Barcelona, 08041

  • Hospital Universitario Ramon y Cajal

    Madrid, 28034

  • Hospital Universitario La Paz - PPDS

    Madrid, 28046

  • Complejo Asistencial Universitario de Salamanca H. Clinico

    Salamanca, 37007

  • Hospital Universitario Virgen del Rocio - PPDS

    Seville, 41013

Other trials in Spain

United Kingdom6 sites

  • University Hospital Birmingham

    Birmingham, B15 2TH

  • Beatson West of Scotland Cancer Centre - PPDS

    Glasgow, Lanarkshire, G12 0YN

  • University College London

    London, London, City of, NW1 2PG

  • Royal Marsden Hospital - Downs Road

    London, London, City of, SW7 3RP

  • Oxford University Hospitals NHS Trust

    Oxford, Oxfordshire, OX3 7LE

  • Derriford Hospital

    Plymouth, Devon, PL6 8DH

Other trials in United Kingdom

Japan5 sites

  • National Cancer Center Hospital East

    Kashiwa, Chiba, 277-8577

  • The Cancer Institute Hospital of Japanese Foundation For Cancer Research

    Koto-Ku, Tokyo, 135-0063

  • National Hospital Organization Nagoya Medical Center

    Nagoya, Aiti, 460-0001

  • Kindai University Hospital

    Osakasayama-Shi, Osaka, 589-0014

  • National University Corporation Tohoku University Tohoku University Hospital

    Sendai, Miyagi, 980-0872

Other trials in Japan

Canada2 sites

  • Centre Hospitalier de l'Universite de Montreal

    Montreal, Quebec, H2L 4M1

  • Sir Mortimer B Davis Jewish General Hospital

    Pointe-Claire, Quebec, H9R 4S3

Other trials in Canada

China2 sites

  • Beijing Cancer Hospital

    Beijing, Beijing Municipality, 100142

  • Shanghai East Hospital

    Shanghai, Shanghai Municipality, 200123

Other trials in China

About this study

Official title: Phase 1/2 Study of TAK-981 in Combination With Rituximab in Patients With Relapsed/Refractory CD20-Positive Non-Hodgkin Lymphoma

This study is about a medicine called TAK-981 given with rituximab, used to treat adults with relapsed or refractory CD20-positive non-Hodgkin lymphoma.

This study has 2 parts.

The main aims of the study are:

  • To check for side effects from treatment with TAK-981 given with rituximab.
  • To check how much TAK-981 participants can tolerate.
  • To check if participants with diffuse large B-cell lymphoma or follicular lymphoma respond well to treatment.

Participants will receive TAK-981 and rituximab in 21-day cycles. They will continue treatment for about 12 months unless their condition gets worse (disease progression), they cannot tolerate the treatment, or they leave the study for certain reasons.

Read the detailed description

The drug being tested in this study is called TAK-981 in combination with rituximab. The study will include a dose escalation phase (Phase 1) and an expansion phase in select non-Hodgkin lymphoma (NHL) indications (Phase 2).

The study will enroll approximately 180 participants, approximately 35 participants in Phase 1 and approximately 145 participants in Phase 2. The participants with indolent or aggressive relapsed or refractory (r/r) NHL in Phase 1 will identify the maximum tolerated dose (MTD) and/or pharmacologically active dose (PAD). PAD can be defined retrospectively once MTD is reached and it can below MTD or coincide with it. In the dose escalation phase, the starting dose of TAK-981 will be 10 mg. The RP2D will be determined based on the available safety, preliminary pharmacokinetic (PK), pharmacodynamic information data, and after any early antitumor activity observed along with the statistical inference from the Bayesian logistic regression modeling (BLRM).

Participants in the Phase 2 will be enrolled once the Phase 1 of the study is completed, and MTD and/or PAD is determined. Phase 2 will explore the efficacy and safety of TAK-981 in combination with rituximab in participants with select NHL types and indications. Participants in Phase 2 will be enrolled in one of the three treatment arms based on Cohorts:

  • Phase 2, Cohort A r/r DLBCL Progressed after CAR T-cell therapy:TAK-981+Rituximab
  • Phase 2, Cohort B:r/r DLBCL;no CAR T-cell Therapy;2-3 Prior Lines: Two Dose Levels of TAK-981+Rituximab
  • Phase 2, Cohort C:r/r FL;no CAR T-cell Therapy;2-3 Prior Lines: Two Dose Levels of TAK-981+Rituximab

This multi-center trial will be conducted worldwide. The overall time to participate in this study is approximately 72 months. Participants will make multiple visits to the clinic, and will attend the end of treatment (EOT) visit 30 days after receiving their last dose of drug or before the start of subsequent systemic anticancer therapy, whichever occurs first for a follow-up assessment.

Being tested
TAK-981, Rituximab
Keywords
Drug Therapy
Medical subject headings
Lymphoma, Non-Hodgkin

What participants receive

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

  • TAK-981Drug

    TAK-981 intravenous infusion.

  • RituximabDrug

    Rituximab intravenous infusion.

Study groups in NCT04074330
Study groupRoleWhat they receive
Phase 1: TAK-981 10mg QWExperimentalParticipants with indolent or aggressive non-Hodgkin lymphoma (NHL) received TAK-981 10 mg, infusion, intravenously (IV), once weekly (QW) on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 milligram per square meter (mg/m^2), infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or disease progression (PD) or unacceptable toxicity.
Receives: Drug: TAK-981; Drug: Rituximab
Phase 1: TAK-981 40mg QWExperimentalParticipants with indolent or aggressive NHL received TAK-981 40 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
Receives: Drug: TAK-981; Drug: Rituximab
Phase 1: TAK-981 60mg QWExperimentalParticipants with indolent or aggressive NHL received TAK-981 60 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
Receives: Drug: TAK-981; Drug: Rituximab
Phase 1: TAK-981 90mg QWExperimentalParticipants with indolent or aggressive NHL received TAK-981 90 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
Receives: Drug: TAK-981; Drug: Rituximab
Phase 1: TAK-981 90mg BIWExperimentalParticipants with indolent or aggressive NHL received TAK-981 90 mg, infusion, IV, BIW on Days 1, 4, 8, and 11 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
Receives: Drug: TAK-981; Drug: Rituximab
Phase 1: TAK-981 120mg QWExperimentalParticipants with indolent or aggressive NHL received TAK-981 120 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
Receives: Drug: TAK-981; Drug: Rituximab
Phase 1: Japan Lead-in: TAK-981 60mg QWExperimentalJapanese participants with indolent or aggressive NHL received TAK-981 60 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
Receives: Drug: TAK-981; Drug: Rituximab
Phase 1: Japan Lead-in: TAK-981 60mg BIWExperimentalJapanese participants with indolent or aggressive NHL received TAK-981 60 mg, infusion, IV, BIW on Days 1, 4, 8, and 11 every 21 days in each 21-day treatment cycle for up to 12 months or PD or unacceptable toxicity.
Receives: Drug: TAK-981
Phase 2 (A): TAK-981 120 mgExperimentalParticipants with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) received TAK-981 120 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab infusion, intravenously, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
Receives: Drug: TAK-981; Drug: Rituximab
Phase 2 (C): TAK-981 120 mgExperimentalParticipants with follicular lymphoma (FL) received TAK-981 120 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab infusion, intravenously, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
Receives: Drug: TAK-981; Drug: Rituximab

What is being measured

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

  1. Phase 1: Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs)

    Adverse event (AE) means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product. A TEAE was defined as an adverse event which occurred on or after the first dose of study drug and no more than 30 days after the last dose of study drug.

    Measured: From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months)

  2. Phase 1: Number of Participants With Grade 3 or Higher TEAEs

    AE means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product whether or not it is related to the medicinal product. A TEAE was defined as an adverse event which occurred on or after the first dose of study drug and no more than 30 days after the last dose of study drug. A severity grade was evaluated as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0, except for Cytokine Release Syndrome (CRS), which was assessed by American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading criteria.

    Measured: From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months)

  3. Phase 1: Duration of TEAEs

    AE means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product whether or not it is related to the medicinal product. A TEAE was defined as an adverse event which occurred on or after the first dose of study drug and no more than 30 days after the last dose of study drug. As per planned analysis, data for this outcome measure were collected and analyzed for the combined population (Phase 1: TAK-981 60mg QW+Japan Lead-in: TAK-981 60mg QW) based on regimen in which same dose groups in Phase 1 irrespective of nationality were pooled.

    Measured: From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months)

  4. Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) Per Dose Level

    DLTs were evaluated according to NCI CTCAE, Version 5.0.

    Measured: Up to 42 months

  5. Phase 2: Overall Response Rate (ORR)

    ORR was defined as the percentage of participants who achieved complete response (CR) and partial response (PR), as defined by the investigator according to Lugano classification for lymphomas during the study.

    Measured: Up to 42 months

Secondary outcomes (23)

  1. Cmax: Maximum Observed Plasma Concentration for TAK-981

    As per planned analysis, data for this outcome measure were collected and analyzed for the combined population (Phase 1: TAK-981 60mg QW+Japan Lead-in: TAK-981 60mg QW) based on regimen in which same dose groups in Phase 1 irrespective of nationality were pooled. This outcome measure was planned to be analyzed for Phase 1 only.

    Measured: Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days)

  2. Tmax: Time of First Occurrence of the Maximum Plasma Concentration (Cmax) for TAK-981

    As per planned analysis, data for this outcome measure were collected and analyzed for the combined population (Phase 1: TAK-981 60mg QW+Japan Lead-in: TAK-981 60mg QW) based on regimen in which same dose groups in Phase 1 irrespective of nationality were pooled. This outcome measure was planned to be analyzed for Phase 1 only.

    Measured: Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days)

  3. AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-981

    As per planned analysis, data for this outcome measure were collected and analyzed for the combined population (Phase 1: TAK-981 60mg QW+Japan Lead-in: TAK-981 60mg QW) based on regimen in which same dose groups in Phase 1 irrespective of nationality were pooled. This outcome measure was planned to be analyzed for Phase 1 only.

    Measured: Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days)

  4. AUC0-∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981

    As per planned analysis, data for this outcome measure were collected and analyzed for the combined population (Phase 1: TAK-981 60mg QW+Japan Lead-in: TAK-981 60mg QW) based on regimen in which same dose groups in Phase 1 irrespective of nationality were pooled. This outcome measure was planned to be analyzed for Phase 1 only.

    Measured: Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days)

  5. t1/2z: Terminal Disposition Phase Half-life for TAK-981

    As per planned analysis, data for this outcome measure were collected and analyzed for the combined population (Phase 1: TAK-981 60mg QW+Japan Lead-in: TAK-981 60mg QW) based on regimen in which same dose groups in Phase 1 irrespective of nationality were pooled. This outcome measure was planned to be analyzed for Phase 1 only.

    Measured: Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days)

  6. CL: Total Clearance After Intravenous Administration for TAK-981

    As per planned analysis, data for this outcome measure were collected and analyzed for the combined population (Phase 1: TAK-981 60mg QW+Japan Lead-in: TAK-981 60mg QW) based on regimen in which same dose groups in Phase 1 irrespective of nationality were pooled. This outcome measure was planned to be analyzed for Phase 1 only.

    Measured: Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days)

  7. Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981

    As per planned analysis, data for this outcome measure were collected and analyzed for the combined population (Phase 1: TAK-981 60mg QW+Japan Lead-in: TAK-981 60mg QW) based on regimen in which same dose groups in Phase 1 irrespective of nationality were pooled. This outcome measure was planned to be analyzed for Phase 1 only.

    Measured: Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days)

  8. Phase 1: Overall Response Rate (ORR)

    ORR is defined as the percentage of participants who achieved CR and PR, as defined by the investigator according to Lugano classification for lymphomas during the study.

    Measured: Up to 42 months

  9. Phase 1: Disease Control Rate (DCR)

    DCR is defined as the percentage of participants who achieved CR, PR, and stable disease (SD) as defined by the investigator according to Lugano classification for Lymphomas during the study.

    Measured: Up to 42 months

  10. Phase 1: Duration of Response (DOR)

    DOR is the time from the date of first documentation of a PR or better to the date of first documentation of PD for responders (PR or better). DOR was assessed by the investigator according to Lugano classification for lymphoma during the study.

    Measured: Up to 42 months

  11. Phase 1: Time to Progression (TTP)

    TTP is defined as the time from the date of first study drug administration to the date of first documented disease progression. TTP was assessed by the investigator according to Lugano classification for lymphoma during the study.

    Measured: Up to 42 months

  12. Phase 1: Progression-Free Survival (PFS)

    PFS is defined as the time from the date of the first dose administration to the date of first documentation of PD or death due to any cause, whichever occurs first. PD was determined by Response Evaluation Criteria in Lymphoma. PFS was assessed by the investigator according to Lugano classification for lymphoma during the study.

    Measured: Up to 42 months

  13. Phase 1: Fold Change From Baseline in Levels of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Blood as Assessed by Flow Cytometry During Phase 1

    The level of TAK-981-SUMO adduct formation was evaluated as the percentage of adduct formed in blood. Positive change denotes improvement.

    Measured: Cycle 1 Day 1 (1 hour, 4 hours, 8 hours) and Day 8 (Pre-dose, 1 hour, 4 hours and 8 hours) (Cycle length = 21 days)

  14. Phase 1: Levels of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Skin as Assessed by Immunohistochemistry (IHC) During Phase 1

    The level of TAK-981-SUMO adduct formation was evaluated as the percentage of adduct formed in skin.

    Measured: Cycle 1 Days 1 and 8 (Cycle length = 21 days)

  15. Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1

    SUMO pathway inhibition in blood was evaluated by flow cytometry with an antibody recognizing SUMO2/3 chains.

    Measured: Cycle 1 Day 1 (1 hour, 4 hours, 8 hours) and Day 8 (Pre-dose, 1 hour, 4 hours and 8 hours) (Cycle length = 21 days)

  16. Phase 1: SUMO Pathway Inhibition in Skin as Assessed by Immunohistochemistry (IHC) During Phase 1

    SUMO pathway inhibition in skin was evaluated with skin tissue biopsies by IHC.

    Measured: Cycle 1 Days 1 and 8 (Cycle length = 21 days)

  17. Phase 2: Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs)

    Adverse event (AE) means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product. A TEAE was defined as an adverse event which occurred on or after the first dose of study drug and no more than 30 days after the last dose of study drug.

    Measured: From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months)

  18. Phase 2: Number of Participants With Grade 3 or Higher TEAEs

    AE means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product whether or not it is related to the medicinal product. A TEAE was defined as an adverse event which occurred on or after the first dose of study drug and no more than 30 days after the last dose of study drug. A severity grade was evaluated as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0, except for Cytokine Release Syndrome (CRS), which was assessed by American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading criteria.

    Measured: From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months)

  19. Phase 2: Duration of TEAEs

    AE means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product whether or not it is related to the medicinal product. A TEAE was defined as an adverse event which occurred on or after the first dose of study drug and no more than 30 days after the last dose of study drug.

    Measured: From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months)

  20. Phase 2: Disease Control Rate (DCR)

    CR is defined as the percentage of participants who achieved CR, PR, and SD as defined by the investigator according to Lugano classification for Lymphomas during the study.

    Measured: Up to 42 months

  21. Phase 2: Duration of Response (DOR)

    DOR is the time from the date of first documentation of a PR or better to the date of first documentation of PD for responders (PR or better). DOR was assessed by the investigator according to Lugano classification for lymphoma during the study.

    Measured: Up to 42 months

  22. Phase 2: Time to Progression (TTP)

    TTP is defined as the time from the date of first study drug administration to the date of first documented disease progression. TTP was assessed by the investigator according to Lugano classification for lymphoma during the study.

    Measured: Up to 42 months

  23. Phase 2: Progression-Free Survival (PFS)

    PFS is defined as the time from the date of the first dose administration to the date of first documentation of PD or death due to any cause, whichever occurs first. PD was determined by Response Evaluation Criteria in Lymphoma. PFS was assessed by the investigator according to Lugano classification for lymphoma during the study.

    Measured: Up to 42 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 Aug 2019
  2. Study start15 Oct 2019
  3. Primary completion26 Apr 2023
  4. Study completion26 Apr 2023

Why it stopped: Enrolment Challenges

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04074330
Sponsor's protocol ID
TAK-981-1501
Other IDs
U1111-1236-0243, 2020-003946-36
Status last verified
May 2024
First submitted
28 Aug 2019
Last updated
14 Jun 2024
Data monitoring committee
Yes
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.

Publications

  • Nakamura A, Grossman S, Song K, Xega K, Zhang Y, Cvet D, Berger A, Shapiro G, Huszar D. The SUMOylation inhibitor subasumstat potentiates rituximab activity by IFN1-dependent macrophage and NK cell stimulation. Blood. 2022 May 5;139(18):2770-2781. doi: 10.1182/blood.2021014267.

    PubMed 35226739

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing TAK-981 and Rituximab in people with Lymphoma, Non-Hodgkin, run by Takeda at 59 sites in 9 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 23 inclusion and 18 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 14 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 59 sites in United States, Italy, France, Germany, Spain and 4 more countries. 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 combined 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.

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 14 Jun 2024). 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?

Phase 1: Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs) (time frame: From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months)). The study lists 5 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 NCT04074330, which also lists 1 linked publication.

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 14 Jun 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in