Response Adapted Incorporation of Tislelizumab Into the Front-line Treatment of Older Patients With Hodgkin lYmphoma

NCT05627115 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: UCL 1432422022-003677-37
• Study Type: interventional
• Target: 80
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to test the effect of tislelizumab treatment in patients with Hodgkin lymphoma. The main question it aims to answer is whether including a drug called tislelizumab in first-line treatment of Hodgkin lymphoma for patients age 60 years and older is effective and well-tolerated. Participants will initially receive tislelizumab infusion every 21 days for 3 doses. After this a PET scan will be performed to assess the response. The subsequent treatment patients receive will depend on the following factors:

1. 1.The lymphoma stage (early stage or advanced stage)
2. 2.The presence or absence of specific high-risk features at the time of diagnosis
3. 3.How well the lymphoma responds to the initial 3 doses of tislelizumab

Conditions

Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Two-year event-free survival (EFS)

  To determine the effect of tislelizumab on 2 year EFS using a response-adapted approach to treatment in the front-line treatment of older patients with Hodgkin lymphoma

  2 years after start of treatment

Secondary Outcomes (13)

• The number / percentage of patients with the worst grade of each adverse event

  From signing of informed consent until 30 calendar days post last IMP or post last investigational treatment administration (or after this date if the site investigator feels the event is related to an IMP and/or investigational treatment)

• PET-defined response rates

  After 3 cycles of tislelizumab (PET1) and at the end of the initial treatment (PET2) - up to 2 years after start of treatment

• Overall survival (OS) of the whole population

  From the date of registration until the date of death (any cause) or the date last seen (patients alive at time of analysis).

• Progression free survival (PFS) of the whole population

  2 years after start of treatment

• EFS in early versus late stage patients

  Up to 2 years after start of treatment

Study Arms (1)

Tislelizumab Response-Adapted Treatment

EXPERIMENTAL

All patients will receive 3 cycles of tislelizumab 200 mg (IV) every 21 days. They will then undergo a PET-CT scan (PET1). Subsequent treatment with further tislelizumab, radiotherapy, and between 2-6 cycles of chemotherapy (Doxorubicin, Vinblastine, and Dacarbazine - AVD) is determined by the patient's stage and response at PET1.

Drug: Tislelizumab, AVD, Radiotherapy

Interventions

Tislelizumab, AVD, Radiotherapy DRUG

GROUP A: Early stage disease without adverse features in CMR: 2 further cycles tislelizumab then radiotherapy then 200mg IV tislelizumab once every 3 weeks until a maximum of 2 years total treatment. PET-CT (PET2) 12 weeks after radiotherapy. GROUP B: Early stage disease with adverse features in CMR: 2 cycles of AVD plus tislelizumab then radiotherapy. PET-CT (PET2) 12 weeks after the completion of radiotherapy. GROUP C: All early stage disease not in CMR: 4 cycles of AVD plus tislelizumab then PET-CT and radiotherapy. PET-CT 12 (PET2) weeks after radiotherapy. GROUP D: Advanced stage disease in CMR: 4 cycles of AVD plus tislelizumab then radiotherapy at investigator's discretion. PET-CT (PET2) 12 weeks after radiotherapy. GROUP E: Advanced stage disease not in CMR: 6 cycles of AVD plus tislelizumab then PET-CT then radiotherapy at investigator's discretion. PET-CT (PET2) 12 weeks after radiotherapy.

Also known as: Response-adapted incorporation of tislelizumab

Tislelizumab Response-Adapted Treatment

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed untreated classic Hodgkin lymphoma (Stage I-IV)
• Age 60 years or over
• In the view of the investigator, fit for combination chemotherapy (includes those who would require planned dose reduction although no lower than 50% doxorubicin)
• Written informed consent
• Measurable disease on contrast enhanced CT as defined by Cheson et al., 2014 1 (Nodal lesion of longest diameter 1.5 cm or extranodal lesion of longest diameter 1.0 cm).
• ECOG performance status 0-2
• Adequate bone marrow function (Platelets ≥ 75 x 109/L without platelet transfusion for 72 hours, Neutrophils ≥ 1.0 x 109/L without G-CSF for 7 days)
• Adequate liver function tests (ALT / AST ≤ 2.5 x ULN, total serum bilirubin ≤ 1.5 x ULN)
• Creatinine Clearance ≥ 30 ml/min as defined by the Cockroft-Gault equation
• Adequate cardiac function as determined by a transthoracic echocardiogram demonstrating left ventricular ejection fraction is ≥ 50% and confirming the absence of severe valvular heart disease
• Willing to comply with the contraceptive requirements of the trial
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures

You may not qualify if:

• Nodular lymphocyte predominant Hodgkin lymphoma
• History of autoimmune disorders (with the exception of hypothyroidism, type 1 diabetes, vitiligo, alopecia)
• History of solid organ transplant
• Grade 2 or higher peripheral neuropathy
• Presentation with disease causing symptomatic compression of vital structures (e.g. stridor due to tracheal compression). Other cases of radiological compression of vital structures require discussion with TMG prior to registration
• Women who are pregnant or breastfeeding
• Active hepatitis B or C infection defined by
• Hepatitis B surface antigen positivity OR
• Anti-hepatitis B core antibody positivity with detectable circulating HBV DNA (hepatitis B core antibody patients with undetectable circulating HBV DNA are eligible but must take suitable prophylaxis for reactivation)
• Anti-Hepatitis C antibody positivity unless patient has been treated for hepatitis C and has undetectable HCV RNA
• Known HIV infection
• Positive PCR for SAR-CoV-2 RNA within the 2 weeks prior to registration. Patients with a history of SARS-CoV-2 are required to have a documented negative PCR swab since documented SARS-CoV-2 infection
• Immunosuppressive therapy within the 2 months prior to registration apart from inhaled, intranasal or topical corticosteroids. Systemic corticosteroids are permitted prior to study entry but must be weaned to 10 mg prednisolone / day for a minimum of 7 days prior to cycle 1 day 1
• Live vaccine given within 30 days prior to registration
• Active infection requiring systemic therapy with ongoing symptoms at registration or where the planned duration of therapy would continue beyond cycle 1 day 1

Sponsors & Collaborators

• University College, London: lead
• BeiGene: collaborator

Related Links

• CR UK \& UCL Cancer Trials Centre

MeSH Terms

Conditions

Hodgkin Disease

Interventions

tislelizumab; Radiotherapy

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Prof Graham Collins

  Oxford University Hospitals NHS Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

RATiFY Trial Coordinator

CONTACT

+44 (0)2076799860; ctc.ratify@ucl.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2022
• First Posted: November 25, 2022
• Study Start: March 1, 2024
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2028
• Last Updated: November 29, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share