Efficacy and Safety of Frontline Tislelizumab in Patients With de Novo Hodgkin Lymphoma Unsuitable for Standard Frontline Chemotherapy (FIL_Tisle-HL)

December 1, 2025 updated by: Fondazione Italiana Linfomi - ETS

Efficacy and Safety of Frontline Tislelizumab in Patients With de Novo Hodgkin Lymphoma Unsuitable for Standard Frontline Chemotherapy: a Phase II, Open-label Study

This is a multicenter, prospective, non-randomized, open-label, phase 2 clinical study to evaluate the efficacy and safety of tislelizumab in patients with de novo Hodgkin Lymphoma deemed ineligible to frontline chemotherapy.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Approximately two-thirds of patients with Hodgkin lymphoma (HL) can be cured with standard frontline chemotherapy with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). The majority of new patients present in the second and third decade of life, but at least 25% of de novo cases are in patients older than 65. Elderly patients with HL display dismal outcomes for several reasons: the disease is implicitly more aggressive than in younger adults, with an advanced stage in at least two-thirds of cases and the presence of multiple risk factors for poor outcome (according to the International Prognostic Score). Moreover, patients may show impaired organ function that require chemotherapy dose reductions, treatment delays or drug withdrawal.

Given the difficulty of delivering of full treatment doses to elderly patients and to those with relevant medical comorbidities, there is a need for new and better tolerated agents in this context.

Given the difficulty of delivering of full treatment doses to elderly patients and to those with relevant medical comorbidities, there is a need for new and better tolerated agents in this context. Importantly, no single agent has received approval for this kind of patients, and drugs like gemcitabine and bendamustine - both active in relapsed patients with limited toxicity - have limitations in their prescription. The anti-CD30 immunoconjugate agent brentuximab vedotin (BV) applied in patients older than 60 years and considered unsuitable for frontline chemotherapy, yielded an overall response of 92%, with 73% of patients achieving a complete remission and a median duration of response of 9.1 months.

Immune checkpoint inhibitors, namely nivolumab and pembrolizumab, have been largely tested in patients with relapsed and refractory HL failing both autologous stem cell transplant and BV. Both agents display efficacy in this context, with significant rates of objective responses, which appear to be durable. Along with an acceptable safety profile, both agents have been approved in relapsed and refractory HL, providing a good treatment option for heavily pretreated patients. Tislelizumab (T, BGB-A317) is a humanized IgG4 mAb with high affinity and specificity for programmed cell death protein 1 (PD1), showing a superior antitumor activity compared to nivolumab in mice transplanted with human cancer cells and peripheral blood mononuclear cells. High response rates have been reported in Chinese HL patients who have failed or were ineligible to autologous transplantation, including a complete response rate of 61% and a partial response rate of 24%.

Investigators postulate that an induction based on single-agent tislelizumab can be a feasible chemo-free treatment strategy to be offered to patients with de novo HL who are unsuitable for a chemotherapy-based frontline approach.

The study also addresses biological evaluation of biomarkers in the tumor clone and in the microenvironment at baseline and their possible correlation with patients' outcome and responses.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
28

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Italy
      • Aviano, Italy
        • Recruiting
        • Divisione di Oncologia e dei Tumori immuto-correlati, Centro Di Riferimento Oncologico Di Aviano
        • Contact:
        • Principal Investigator:
          • Michele Spina, MD
      • Bologna, Italy
        • Recruiting
        • Istituto di Ematologia L. e A. Seràgnoli, AOU Policlinico S. Orsola-Malpighi
        • Principal Investigator:
          • Pier Luigi Zinzani, MD
        • Contact:
      • Brescia, Italy
        • Recruiting
        • SC Ematologia, Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
        • Contact:
        • Principal Investigator:
          • Alessandra Tucci, MD
      • Milan, Italy
        • Recruiting
        • Ematologia, Fondazione IRCCS Istituto Nazionale Dei Tumori
        • Contact:
        • Principal Investigator:
          • Chiara Rusconi, MD
      • Milan, Italy
        • Recruiting
        • Unità di Ematologia e TMO - Unità Linfomi, Ospedale San Raffaele
        • Principal Investigator:
          • Andrés J.M. Ferreri, MD
        • Contact:
      • Napoli, Italy
        • Recruiting
        • Oncologia, IRCCS Istituto Nazionale Tumori Fondazione Pascale
        • Principal Investigator:
          • Antonio Pinto, MD
        • Contact:
      • Palermo, Italy
        • Not yet recruiting
        • Oncoematologia, Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
        • Contact:
        • Principal Investigator:
          • Caterina Patti, MD
      • Roma, Italy
        • Recruiting
        • Istituto Ematologia -Dipartimento di Medicina Traslazionale e di Precisione, Azienda Ospealiero Universitaria Policlinico Umberto I
        • Contact:
        • Principal Investigator:
          • Ilaria Del Giudice, MD
      • Rozzano, Italy
        • Recruiting
        • U.O di Oncologia Medica ed Ematologia, Humanitas Research Hospital
        • Contact:
        • Principal Investigator:
          • Francesca Ricci, MD
    • IT
      • Alessandria, IT, Italy
        • Recruiting
        • A.O. SS. Antonio e Biagio e Cesare Arrigo, S.C. Ematologia
        • Contact:
        • Principal Investigator:
          • Manuela Zanni, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically confirmed diagnosis of de novo classical Hodgkin Lymphoma (cHL). Note: Availability of either block or unstained slides plus stained slides used by the local pathologist to make diagnosis, and of all pathology reports is mandatory for the study to perform central pathology review for confirmation of cHL diagnosis and for biological biomarkers assessments. Central pathology confirmation is not required to start treatment;
  • Patients >= 65 years ineligible for frontline standard chemotherapy (mainly due to medical comorbidities);
  • Treatment naïve;
  • Measurable disease defined as presence of both fluorodeoxyglucose-avid nodal involvement and at least one nodal target lesion measurable in two diameters (and at least 1.5 cm in its major diameter); • Indication for systemic treatment, i.e., all stages except IA without a large tumor burden, as radiotherapy is regarded curative in those patients;
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) <= 2;

  • Adequate organ and marrow function as defined below:

    • Absolute neutrophil count (ANC) > 109/L (without growth factor support within 7 days of ANC measurement), unless due to bone marrow involvement by lymphoma
    • Platelet > 50 x 109/L (without growth factor support or transfusion within 7 days of platelets measurement) , unless due to bone marrow involvement by lymphoma
    • Hemoglobin > 8 g/dL (prior transfusion is acceptable)
    • Creatinine clearance ≥ 30 ml/min (as estimated by the Cockcroft-Gault equation or as measured by nuclear medicine scan or 24-hour urine collection)
    • Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase, and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase ≤ 3.0 × upper limit of normal (ULN)
    • Serum total bilirubin < 1.5 × ULN (or < 3 x ULN in case of documented Gilbert's syndrome)
  • Life expectancy ≥ 6 months;
  • Men must agree to use effective contraception if sexually active. This applies for the time period between signing of the informed consent form and 4 months after last tislelizumab dose. The investigator or a designated associate is requested to advise the patient how to achieve highly effective birth control method, e.g. vasectomy, use of condoms or complete sexual abstinence, when this is in line with the preferred and usual lifestyle of the subject.The use of condoms by male patients is required unless the female partner is permanently sterile. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post ovulation methods for the female partner) and withdrawal are not acceptable methods of contraception.
  • Subject voluntarily signs and dates an informed consent form approved by an National Ethics Committee (NEC) prior to the initiation of any screening or study-specific procedures, indicating that they understand the purpose of and procedures required for the study and are willing to participate in it;
  • Subject must be able to adhere to the study visit schedule and other protocol requirements, and to return to enrolling institution for follow-up (during the active monitoring phase of the study).

Exclusion Criteria:

  • Nodular lymphocyte predominant HL;
  • Any previous treatment (including radiation therapy) for HL;
  • Any active autoimmune disease requiring systemic treatment (including disease-modifying agents, corticosteroids, immunosuppressants) in the past 2 years; Note: Patients with the following diseases are not excluded and may proceed to further screening: Type I diabetes under control; Hypothyroidism (provided it is managed with hormone replacement therapy only); Controlled celiac disease;
  • Has known history of interstitial lung disease, non-infectious pneumonitis, pulmonary fibrosis, acute lung diseases or evidence of dyspnea at rest or pulse oximetry of < 92% while breathing room air;
  • A history of previous exposure to anti-PD1, anti-PDL1 or anti-PDL2 or anti-CTLA-4 agents for any disease other than HL;
  • Use of systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications ≤14 days from registration; Note: Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease;
  • Known infection with HIV, human T-cell lymphotropic virus-1, -2; • Serologic status reflecting active hepatitis B defined as presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) (mandatory testing). Patients with occult or prior HBV infection (respectively defined as patient with HBsAg-/HBcAb+ and patients HBsAg+ with HBV DNA undetectable) are eligible, provided that they are willing to undergo prophylactic antiviral medication according to local standard of care. Patients who have protective titers of hepatitis B surface antibody (HBsAb) after vaccination are eligible;
  • Presence of hepatitis C virus (HCV) antibody (mandatory HCV antibody serology testing). Patients with presence of HCV antibody are eligible only if PCR is negative for HCV RNA;
  • Hypersensitivity to tislelizumab or any of its excipients;
  • Active central nervous system (CNS) involvement or leptomeningeal metastases involvement;
  • Evidence of other clinically significant uncontrolled and/or active systemic infection (viral, bacterial or fungal), including active ongoing infection from SARS-CoV-2;
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens;
  • Major surgery within 4 weeks of the first dose of study drug;
  • Vaccination with a live vaccine within 4 weeks prior to the first dose of study drug;

  • Clinically significant cardiovascular disease including the following:

    • Myocardial infarction within 6 months before screening;
    • Unstable angina within 3 months before screening;
    • New York Heart Association Classification III or IV congestive heart failure;
    • History of clinically significant arrhythmias (e.g., sustained ventricular tachycardia, ventricular fibrillation, torsade de pointes);
    • QTcF > 480 msecs based on Fridericia's formula;
    • History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place;
    • Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood pressure measurements showing systolic blood pressure > 170 mm Hg and diastolic blood pressure > 105 mm Hg at screening;
  • Significant history of neurologic, psychiatric, endocrinological, metabolic, immunologic, or hepatic disease that would preclude participation in the study or compromise ability to give informed consent;
  • Any history of other active malignancies within 3 years prior to study entry, with the exception of adequately treated in situ carcinoma of the cervix uterine, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin, previous malignancy confined and surgically resected with curative intent;
  • History of severe hypersensitivity reactions to other monoclonal antibodies;
  • Concurrent participation in another therapeutic clinical trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Tislelizumab
Tislelizumab single dose every 3 weeks up to 35 total administration
Drug: Tislelizumab
Tislelizumab 200mg IV day1

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall Response Rate (CR + PR)
Time Frame: From treatment start up to about 24 months
The primary endpoint of the study is the ORR (the sum of complete response (CR) and partial response (PR) rate).
From treatment start up to about 24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Duration of response (DoR)
Time Frame: Between +33 days after treatment start up to 66 months
Time from first documented complete response according to Lugano and LYRIC criteria to disease relapse.
Between +33 days after treatment start up to 66 months
Progression-free survival (PFS)
Time Frame: From registration up to 66 months
Time from registration to the earliest date of documentation of disease progression, relapse or death from any cause.
From registration up to 66 months
Overall survival (OS)
Time Frame: From registration up to 66 months
Time from registration to death from any cause.
From registration up to 66 months
Disease free survival (DFS)
Time Frame: Between +33 days after treatment start up to 66 months
Time from first documented complete response according to Lugano and LYRIC criteria to disease relapse or death as a result of lymphoma or acute toxicity of treatment.
Between +33 days after treatment start up to 66 months
Incidence and severity of adverse events occurred during therapy and up to 90 days after treatment and incidence and severity of serious adverse events occurred from the IC signed to the end of the study (LPLV)
Time Frame: From treatment start up to 66 months
To evaluate the safety and tolerability of tislelizumab
From treatment start up to 66 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fondazione Italiana Linfomi - ETS

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Pier Luigi Zinzani, MD, Istituto di Ematologia "L. e A. Seràgnoli", AOU Policlinico S.Orsola-Malpighi, Bologna

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 23, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 28, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 3, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 4, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 8, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 1, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • FIL_Tisle-HL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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