Non Hodgkin Lymphoma Clinical Trial

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

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.
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.

View Full Description

Full 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.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Each participant must meet all the following inclusion criteria to be enrolled in the study:

Participant Population:

o. 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.

o. 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.

o. 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, weekly*4 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.

o. 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).

o. 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).

o. 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 (>=) 75.0*10^9/L, Grade 2 thrombocytopenia (platelet count >=50.0*10^9 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) >=1.0*10^9/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]).

Exclusion Criteria:

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.
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.

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 1

Estimated Enrollment:

180

Study ID:

NCT04074330

Recruitment Status:

Active, not recruiting

Sponsor:

Takeda

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There are 59 Locations for this study

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University of Alabama at Birmingham
Birmingham Alabama, 35294, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor Michigan, 48109, United States
Mayo Clinic - Cancer Center - Rochester - PPDS
Rochester Minnesota, 55905, United States
Levine Cancer Institute - Charlotte
Chapel Hill North Carolina, 27514, United States
East Carolina University
Greenville North Carolina, 27834, United States
University of Cincinnati
Cincinnati Ohio, 45219, United States
University Hospitals Cleveland Medical Center
Cleveland Ohio, 44106, United States
Ohio State University Wexner Medical Center
Columbus Ohio, 43210, United States
City of Hope - Comprehensive Cancer Center (CCC)
Portland Oregon, 97239, United States
Western Pennsylvania Hospital
Pittsburgh Pennsylvania, 15224, United States
Texas Oncology (Medical City) - USOR
Dallas Texas, 75230, United States
Texas Oncology (Tyler) - USOR
Tyler Texas, 75702, United States
Centre Hospitalier de l'Universite de Montreal
Montreal Quebec, H2L 4, Canada
Sir Mortimer B Davis Jewish General Hospital
Pointe-Claire Quebec, H9R 4, Canada
Beijing Cancer Hospital
Beijing Beijing, 10014, China
Shanghai East Hospital
Shanghai Shanghai, 20012, China
Institut Paoli Calmettes
Marseille Bouches-du-Rhone, 13273, France
Hopital Francois Mitterand
Dijon Cote-d'Or, 21000, France
CHU Montpellier - Hopital St Eloi
Montpellier Herault, 34090, France
Hopital Prive Sevigne
Rennes Ille-et-Vilaine, 35000, France
Hotel Dieu - Nantes
Nantes Loire-Atlantique, 44093, France
Centre Henri Becquerel
Rouen Seine-Maritime, 76038, France
Hopital Saint Antoine
Paris , 75012, France
Hopital Universitaire Pitie Salpetriere
Paris , 75013, France
Universitatsklinikum Freiburg
Freiburg Baden-Wurttemberg, 79106, Germany
Universitatsklinikum Tubingen
Tubingen Baden-Wurttemberg, 72076, Germany
Klinikum rechts der Isa der Technischen Universitaet Muenchen
Munchen Bayern, 81675, Germany
Universitatsklinikum Wurzburg
Wurzburg Bayern, 97080, Germany
Universitatsklinikum Essen
Essen Nordrhein-Westfalen, 45147, Germany
Otto-von-Guericke-Universitat Magdeburg
Magdeburg Sachsen-Anhalt, 39120, Germany
Universitatsklinikum Leipzig
Leipzig Sachsen, 04103, Germany
Charite - Universitatsmedizin Berlin
Berlin , 12203, Germany
Azienda Sanitaria Locale di Ravenna
Ravenna Emilia-Romagna, 48100, Italy
Azienda Ospedaliera San Camillo Forlanini
Roma Lazio, 00152, Italy
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Milano Lombardia, 20122, Italy
Istituto Nazionale Dei Tumori
Milano Lombardia, 20133, Italy
ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda
Milano Lombardia, 20162, Italy
A.O.U. Maggiore della Carita
Novara Piemonte, 28100, Italy
Azienda Ospedaliera Citta della Salute e della Scienza di Torino
Torino Piemonte, 10126, Italy
Azienda Ospedaliera Cardinale G Panico
Tricase Puglia, 73039, Italy
Fondazione IRCCS Policlinico San Matteo di Pavia
Pavia , 27100, Italy
National Hospital Organization Nagoya Medical Center
Nagoya-Shi Aiti, 460-0, Japan
National University Corporation Tohoku University Tohoku University Hospital
Sendai-Shi Miyagi, 980-0, Japan
Kindai University Hospital
Osakasayama-Shi Osaka, 589-0, Japan
National Cancer Center Hospital East
Kashiwa Tiba, 277-8, Japan
The Cancer Institute Hospital of Japanese Foundation For Cancer Research
Koto-Ku Tokyo, 135-0, Japan
Hospital Clinic de Barcelona
Barcelona , '0803, Spain
Hospital del Mar
Barcelona , 08003, Spain
Hospital de La Santa Creu i Sant Pau
Barcelona , 08041, Spain
Hospital Universitario Ramon y Cajal
Madrid , 28034, Spain
Hospital Universitario La Paz - PPDS
Madrid , 28046, Spain
Complejo Asistencial Universitario de Salamanca H. Clinico
Salamanca , 37007, Spain
Hospital Universitario Virgen del Rocio - PPDS
Sevilla , 41013, Spain
Derriford Hospital
Plymouth Devon, PL6 8, United Kingdom
Beatson West of Scotland Cancer Centre - PPDS
Glasgow Lanarkshire, G12 0, United Kingdom
University College London
London London, City Of, NW1 2, United Kingdom
Royal Marsden Hospital - Downs Road
London London, City Of, SW7 3, United Kingdom
Oxford University Hospitals NHS Trust
Oxford Oxfordshire, OX3 7, United Kingdom
University Hospital Birmingham
Birmingham , B15 2, United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 1

Estimated Enrollment:

180

Study ID:

NCT04074330

Recruitment Status:

Active, not recruiting

Sponsor:


Takeda

How clear is this clinincal trial information?

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