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

Korábbi kezelés

• 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
• 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
• Major surgery within 4 weeks prior to registration (excisional biopsy is not considered major surgery)
• Myocardial infarction, unstable angina, coronary artery bypass graft, cerebrovascular accident or transient ischaemic attack within 6 months prior to registration
• Previously treated haematological malignancy
• Patient not fit for AVD chemotherapy in the opinion of the investigator

Más betegség

• History of autoimmune disorders (with the exception of hypothyroidism, type 1 diabetes, vitiligo, alopecia)
• History of solid organ transplant
• 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
• Active infection requiring systemic therapy with ongoing symptoms at registration or where the planned duration of therapy would continue beyond cycle 1 day 1
• 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:
  • Adequately treated non-melanoma skin cancer considered to be in remission
  • Melanoma in situ following resection
  • Carcinoma in situ of the breast or cervix
  • Carcinoma of the prostate of Gleason grade 6 or less with stable prostate-specific antigen levels
  • 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
• A history of other malignancies should be discussed with the trial management group prior to registration

Laborértékek

• Nodular lymphocyte predominant Hodgkin lymphoma

Egyéb

• Grade 2 or higher peripheral neuropathy
• Women who are pregnant or breastfeeding

• 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