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

• Status: Not yet recruiting
• Trial end date: 2027-09-01
• Target enrollment: 0
• Participant gender: All

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. The lymphoma stage (early stage or advanced stage)

2. The presence or absence of specific high-risk features at the time of diagnosis

3. How well the lymphoma responds to the initial 3 doses of tislelizumab

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University College, London
• Collaborator: BeiGene

Criteria

Inclusion Criteria:

1. Newly diagnosed untreated classic Hodgkin lymphoma (Stage I-IV)

2. Age 60 years or over

3. In the view of the investigator, fit for combination chemotherapy (includes those who would require planned dose reduction although no lower than 50% doxorubicin)

4. Written informed consent

5. 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).

6. ECOG performance status 0-2

7. 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)

8. Adequate liver function tests (ALT / AST ≤ 2.5 x ULN, total serum bilirubin ≤ 1.5 x ULN)

9. Creatinine Clearance ≥ 30 ml/min as defined by the Cockroft-Gault equation

10. 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

11. Willing to comply with the contraceptive requirements of the trial

12. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures

Exclusion Criteria:

1. Nodular lymphocyte predominant Hodgkin lymphoma

2. History of autoimmune disorders (with the exception of hypothyroidism, type 1 diabetes, vitiligo, alopecia)

3. History of solid organ transplant

4. Grade 2 or higher peripheral neuropathy

5. 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

6. Women who are pregnant or breastfeeding

7. Active hepatitis B or C infection defined by

1. Hepatitis B surface antigen positivity OR

2. 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)

3. Anti-Hepatitis C antibody positivity unless patient has been treated for hepatitis C and has undetectable HCV RNA

8. Known HIV infection

9. 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

10. 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

11. Live vaccine given within 30 days prior to registration

12. Active infection requiring systemic therapy with ongoing symptoms at registration or where the planned duration of therapy would continue beyond cycle 1 day 1

13. Major surgery within 4 weeks prior to registration (excisional biopsy is not considered major surgery)

14. Myocardial infarction, unstable angina, coronary artery bypass graft, cerebrovascular accident or transient ischaemic attack within 6 months prior to registration

15. Previously treated haematological malignancy

16. Solid-organ malignancy active within the last 3 years, except where the natural history or treatment does not have the potential to interfere with assessment of safety or efficacy of trial treatment, for example:

1. Adequately treated non-melanoma skin cancer considered to be in remission

2. Melanoma in situ following resection

3. Carcinoma in situ of the breast or cervix

4. Carcinoma of the prostate of Gleason grade 6 or less with stable prostate-specific antigen levels

5. Cancer considered cured by surgical resection or unlikely to impact survival in the next 3 years, for example local transitional carcinoma of the bladder or benign tumours of the adrenal gland or pancreas

17. A history of other malignancies should be discussed with the trial management group prior to registration

18. Patient not fit for AVD chemotherapy in the opinion of the investigator